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J Clin Oncol. 2024 Sep 1; 42(25): 3000–3011.
Published online 2024 Jun 6. doi:10.1200/JCO.24.00720
PMCID: PMC11361350
PMID: 38843488
D. Ross Camidge, MD, PhD,
1 Jair Bar, MD, PhD,2 Hidehito Horinouchi, MD, PhD,3 Jonathan Goldman, MD,4 Fedor Moiseenko, MD, PhD,5 Elena Filippova, MD,6 Irfan Cicin, MD,7 Tudor Ciuleanu, MD, PhD,8 Nathalie Daaboul, MD,9 Chunling Liu, MD,10 Penelope Bradbury, MD (UK), MB, BCh, FRACP,11 Mor Moskovitz, MD,12 Nuran Katgi, MD,13 Pascale Tomasini, MD,14 Alona Zer, MD,12 Nicolas Girard, MD, PhD,15 Kristof Cuppens, MD,16,17 Ji-Youn Han, MD, PhD,18 Shang-Yin Wu, MD,19,20 Shobhit Baijal, MBBS BSc (Hons), MRCP,21 Aaron S. Mansfield, MD,22 Chih-Hsi Kuo, MD,23 Kazumi Nishino, MD, PhD,24 Se-Hoon Lee, MD, PhD,25 David Planchard, MD, PhD,26,27 Christina Baik, MD, MPH,28 Martha Li, PhD,29 Peter Ansell, PhD,29 Summer Xia, PhD,29 Ellen Bolotin, MD,29 Jim Looman, MD,29 Christine Ratajczak, PhD,29 and Shun Lu, MD, PhD30
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Associated Data
- Data Availability Statement
Abstract
PURPOSE
Telisotuzumab vedotin (Teliso-V) is a c-Met–directed antibody-drug conjugate with a monomethyl auristatin E cytotoxic payload. The phase II LUMINOSITY trial (ClinicalTrials.gov identifier: NCT03539536) aimed to identify the optimal c-Met protein–overexpressing non–small cell lung cancer (NSCLC) population for treatment with Teliso-V (stage I) and expand the selected group for efficacy evaluation (stage II). Stage II enrolled patients with nonsquamous epidermal growth factor receptor (EGFR)-wildtype NSCLC.
METHODS
Eligible patients had locally advanced/metastatic c-Met protein–overexpressing NSCLC and ≤2 previous lines of therapy (including ≤1 line of systemic chemotherapy). c-Met protein overexpression in nonsquamous EGFR-wildtype NSCLC was defined as ≥25% tumor cells with 3+ staining (high [≥50% 3+]; intermediate [≥25%–<50%]). Teliso-V was administered at 1.9 mg/kg once every 2 weeks. The primary end point was overall response rate (ORR) by independent central review.
RESULTS
In total, 172 patients with nonsquamous EGFR-wildtype NSCLC received Teliso-V in stages I and II. ORR was 28.6% (95% CI, 21.7 to 36.2; c-Met high, 34.6% [95% CI, 24.2 to 46.2]; c-Met intermediate, 22.9% [95% CI, 14.4 to 33.4]). The median duration of response was 8.3 months (95% CI, 5.6 to 11.3; c-Met high, 9.0 [95% CI, 4.2 to 13.0]; c-Met intermediate: 7.2 [95% CI, 5.3 to 11.5]). The median overall survival was 14.5 months (95% CI, 9.9 to 16.6; c-Met high, 14.6 [95% CI, 9.2 to 25.6]; c-Met intermediate, 14.2 [95% CI, 9.6 to 16.6]). The median progression-free survival was 5.7 months (95% CI, 4.6 to 6.9; c-Met high, 5.5 [95% CI, 4.1 to 8.3]; c-Met intermediate: 6.0 [95% CI, 4.5 to 8.1]). Most common any-grade treatment-related adverse events (AEs) were peripheral sensory neuropathy (30%), peripheral edema (16%), and fatigue (14%); the most common grade ≥3 AE was peripheral sensory neuropathy (7%).
CONCLUSION
Teliso-V was associated with durable responses in c-Met protein–overexpressing nonsquamous EGFR-wildtype NSCLC, especially in those with high c-Met. AEs were generally manageable.
Durable responses and manageable safety with Teliso-V monotherapy in 2L+ c-Met protein–overexpressing NSCLC
INTRODUCTION
The MET proto-oncogene encodes the c-Met protein (also known as MET protein and hepatocyte growth factor receptor), a receptor tyrosine kinase that mediates cell proliferation, survival, and angiogenesis1-3 and can be dysregulated in non–small cell lung cancer (NSCLC). Aside from any role in acquired resistance to targeted therapies, primary MET gene dysregulation can occur through amplification or mutation in approximately 5% and approximately 2%-4% of patients with NSCLC, respectively.4 c-Met tyrosine kinase inhibitors have been successfully developed for patients with MET exon 14 skipping mutations and are in development for MET amplification.5,6 Approximately 25%-39% of patients with NSCLC have tumors that overexpress the c-Met protein, which may coexist with MET genomic alterations. Overexpression prevalence is approximately 25% in patients with nonsquamous epidermal growth factor receptor (EGFR)-wildtype NSCLC.7,8 c-Met protein overexpression is a negative prognostic factor for survival in early and advanced NSCLC.4,9-11 Although numerous clinical trials are evaluating targeted therapies against cancers with MET genomic alterations, there are currently no therapies available to specifically target c-Met protein overexpression.
CONTEXT
Key Objective
To identify the c-Met protein–overexpressing non–small cell lung cancer (NSCLC) population best suited for telisotuzumab vedotin (Teliso-V) therapy in the second- or third-line setting and to further evaluate Teliso-V efficacy and safety in the selected population.
Knowledge Generated
Teliso-V was associated with durable responses in patients with c-Met protein–overexpressing nonsquamous epidermal growth factor receptor (EGFR)-wildtype NSCLC, especially in those with high c-Met protein expression. Adverse events were generally manageable.
Relevance (T.E. Stinchcombe)
The activity of Teliso-V in patients with nonsquamous EGFR-wildtype NSCLC with MET protein–overexpression informs an ongoing phase III trial of Teliso-V compared with docetaxel in this patient population. The squamous and nonsquamous EGFR mutant cohorts were closed based in the futility criteria.*
*Relevance section written by JCO Associate Editor Thomas E. Stinchcombe, MD.
Telisotuzumab vedotin (Teliso-V) is a first-in-class c-Met–directed antibody-drug conjugate comprising the monoclonal antibody telisotuzumab conjugated to the microtubule inhibitor monomethyl auristatin E (MMAE) via a cleavable dipeptide linker.12 Teliso-V uses c-Met protein overexpression as a biomarker to target the cytotoxic payload to tumor cells and has shown promising activity and an acceptable safety profile in patients with c-Met protein–overexpressing NSCLC in a phase I study.12,13
The phase II LUMINOSITY trial evaluated the efficacy and safety of Teliso-V in patients with c-Met protein–overexpressing locally advanced/metastatic NSCLC. The aim was to identify the population best suited for Teliso-V in the second or third line (stage I) and to further assess the efficacy and safety in the selected population (stage II). The c-Met protein–overexpressing, nonsquamous EGFR-wildtype NSCLC population was selected for further evaluation in stage II. Primary efficacy and safety analyses are reported.
METHODS
Trial Design
LUMINOSITY (ClinicalTrials.gov identifier: NCT03539536) is a phase II, multicenter, nonrandomized, two-stage study (Fig (Fig1).1). Stage I enrolled patients into three cohorts defined by histology and EGFR mutation status: (1) c-Met protein–overexpressing, nonsquamous EGFR-wildtype NSCLC, (2) c-Met protein–overexpressing, nonsquamous EGFR-mutant NSCLC, and (3) c-Met protein–overexpressing squamous NSCLC. By design, stage II enrolled patients in specific group(s) meeting expansion criteria in stage I; patients with c-Met protein–overexpressing, nonsquamous EGFR-wildtype NSCLC were enrolled in stage II. c-Met protein overexpression was measured by immunohistochemistry (clinical trial assay for MET [SP44] [Roche]). For the nonsquamous cohorts, on the basis of correlative analysis of previous phase I efficacy data, overexpression was defined as ≥25% of tumor cells with membrane staining at 3+ intensity (c-Met high, ≥50% of tumor cells with 3+ intensity; c-Met intermediate, ≥25% to <50% of tumor cells with 3+ intensity). In the squamous cohort, where c-Met protein is expressed at a much lower level than in nonsquamous NSCLC, c-Met protein overexpression was defined as 75% of tumor cells with membrane staining at any intensity by immunohistochemistry to ensure approximately 25% of screened patients would be eligible. Prescreening for tumor c-Met protein overexpression on archival or postprogression tissue could occur before the initiation of the screening period. Teliso-V was dosed at 1.9 mg/kg intravenously once every 2 weeks in stages I and II. After completion of stage II global enrollment, a China extension cohort with Teliso-V dosed at 1.9 mg/kg once every 2 weeks was added to meet local regulatory requirements, and another supplementary cohort evaluating Teliso-V at 1.6 mg/kg once every 2 weeks was added, in accordance with the US Food and Drug Administration's Project Optimus initiative focused on dose optimization. Data from the 1.6-mg/kg once every 2 weeks cohort will be reported separately. All patients received Teliso-V until disease progression, intolerable toxicity, or other study discontinuation criteria were met.
FIG 1.
Study design. The nonsquamous EGFR-wildtype cohort was expanded in stage II. A stage II China extension cohort planned to enroll up to 12 patients was added after the global stage II enrollment was complete. In addition, a supplementary cohort evaluating Teliso-V at 1.6 mg/kg q2w in up to approximately 20 patients with nonsquamous EGFR-wildtype NSCLC was added after completion of stage II enrollment. EGFR, epidermal growth factor receptor; NSCLC, non–small cell lung cancer; NSQ, nonsquamous; MU, mutant; OE, overexpressing; q2w, once every 2 weeks; SQ, squamous; Teliso-V, telisotuzumab vedotin; WT, wildtype.
The study was conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice Guidelines of the International Conference on Harmonization and was approved by regulatory and independent ethics committees/institutional review boards at each site. All patients provided written informed consent before any study procedures were performed.
Patients
Adults (age ≥18 years) with locally advanced/metastatic, c-Met protein–overexpressing, nonsquamous NSCLC with known EGFR status or squamous cell NSCLC were enrolled. c-Met protein–overexpressing, nonsquamous EGFR-wildtype NSCLC was required for stage II. Other key eligibility criteria included Eastern Cooperative Oncology Group performance status 0-1, measurable disease per RECIST v1.1, and ≤2 lines of previous systemic therapy in the locally advanced/metastatic setting, including cytotoxic chemotherapy (maximum one line), immunotherapy, and therapy targeting driver gene alterations (if eligible). Patients must not have received previous radiation therapy to the lungs within 6 months of the first dose of Teliso-V. Patients with brain metastases were eligible if the metastases received definitive treatment and were stable. Exclusion criteria included history of interstitial lung disease (ILD) or pneumonitis that required systemic steroid treatment (Appendix Table AA1,1, online only).
Outcomes and Assessments
The primary end point was overall response rate (ORR) by independent central review (ICR) per RECIST v1.1.14 Secondary end points were duration of response (DOR), disease control rate (DCR; per RECIST v1.1), progression-free survival (PFS), and overall survival (OS). Tumor assessments (computed tomography or magnetic resonance imaging) were performed at baseline and approximately every 6 weeks increasing to every 8 weeks after 1 year and every 12 weeks after 2 years. Safety and tolerability were assessed by evaluating adverse events (AEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. AEs were recorded and graded from initial drug administration until 30 days after last administration of Teliso-V. AE terms are as reported by the investigative site according to Medical Dictionary for Regulatory Activities (MedDRA) preferred term. Cases of suspected ILD as reported by the investigative site were also reviewed retrospectively by an adjudication committee and classified as ILD or non-ILD; cases reviewed included investigative site-reported AEs of pneumonitis and ILD, among other related preferred terms.
Statistical Analysis
The planned sample size for stage I was up to 150 patients across the three cohorts and five groups defined by histology, EGFR mutation status, and c-Met protein expression level (Fig (Fig1),1), with up to 30 efficacy-evaluable patients with measurable disease per ICR per group. This sample size was to provide good operating characteristics for go/no-go decision making at stage I for each cohort and group on the basis of comprehensive evaluation via simulations under various scenarios. In stage I, efficacy was evaluated in interim analyses conducted after approximately every additional 30 c-Met protein–overexpressing, efficacy-evaluable patients were enrolled. The ORR (the proportion of patients with a confirmed complete response or a confirmed partial response) for each group was assessed using the Bayesian posterior probability of success, defined as the posterior probability of the ORR exceeding 25%; if this fell below 0.10, the group was considered futile; if this went above 0.70, the group was expanded.
The selected population from stage I was to be expanded to a planned sample size of up to 160 efficacy-evaluable patients enrolled globally by the end of stage II to provide approximately 84% power to rule out a 25% ORR by the lower limit of 95% CI of the estimated ORR at study end, assuming the true ORR for Teliso-V to be 36%. After completion of global enrollment, a stage II China extension cohort to enroll up to approximately 12 patients was opened. Primary analysis occurred 6 months after the first scheduled postbaseline tumor assessment for the last patient enrolled globally in stage II. All patients who received ≥1 dose of Teliso-V at 1.9 mg/kg once every 2 weeks were included in safety analyses. All dosed patients with c-Met protein overexpression enrolled globally in stage I and II or enrolled in the China extension cohort with ≥7.5 months of follow-up after first dose were included in the efficacy analyses.
The primary end point of ORR was summarized along with the two-sided 95% exact CI. Time-to-event end points, including DOR, PFS, and OS, were summarized by median time corresponding to the 50% event probability with two-sided 95% CIs estimated using the Brookmeyer and Crowley method.15 Six-month PFS and 12-month OS were estimated using Kaplan-Meier methodology, along with 95% CI calculated with the SE derived from the Greenwood formula.16 Patients without any postbaseline tumor assessments were considered nonresponders for ORR and DOR. For patients who are progression-free and alive, PFS was censored at the date of last tumor assessment. For patients without any postbaseline tumor assessments who did not die, PFS was censored at the day of the first dose. For patients with no reported death, OS was censored at the last date the patient was known to be alive.
RESULTS
Patients
Across all cohorts, 3,181 patients were prescreened/screened; of the 2,911 (91.5%) patients who did not enter the study, 2,531 did not meet eligibility criteria (79.6%), most commonly because of lack of c-Met protein overexpression. In total, 1,954 evaluable samples were submitted for eligibility prescreening of patients with nonsquamous EGFR-wildtype NSCLC (archival tissue, n = 1,628; postprogression tissue, n = 326); 23.6% were c-Met protein–overexpressing (≥25% 3+ by IHC; archival tissue, 22.1%; postprogression tissue, 31.6%) and 13.5% were c-Met high (≥50% 3+ by IHC; archival tissue, 12.5%; postprogression tissue, 18.1%). Among 28 patients with repeat biopsies available, >90% had the same or higher c-Met overexpression status on repeat biopsy (Appendix 1).
In total, 270 patients enrolled and received ≥1 dose of Teliso-V; 245 received Teliso-V at 1.9 mg/kg once every 2 weeks. There were 172 patients with nonsquamous EGFR-wildtype NSCLC dosed at 1.9 mg/kg once every 2 weeks (c-Met high, n = 84; c-Met intermediate, n = 84; c-Met negative, n = 4); 161 were evaluable for efficacy at the primary analysis (Fig (Fig2).2). Baseline demographics and disease characteristics for patients with nonsquamous EGFR-wildtype NSCLC are shown in Table Table1.1. Patients were predominantly male, White, and current/former tobacco users. The median number of previous therapies was 1 (range, 1-3); 98% of patients had previous platinum-based therapy, and 82% had received an immune checkpoint inhibitor. Appendix Table AA22 summarizes the data for the nonsquamous EGFR-mutated NSCLC (n = 45) and squamous NSCLC (n = 28) cohorts that did not proceed to stage II.
FIG 2.
Among the 172 patients in the safety analysis set for NSQ EGFR WT NSCLC at 1.9 mg/kg q2w, eight were enrolled in the China extension cohort. aAmong 1,954 evaluable submitted samples for prescreening patients for eligibility among those with nonsquamous EGFR-wildtype NSCLC, 23.6% were c-Met protein–overexpressing and 13.5% were c-Met high. bOf the 197 patients with nonsquamous EGFR-wildtype NSCLC, 53 patients were enrolled in stage I of the study. In total, 119 patients were enrolled in stage II: global enrollment, n = 111; China extension cohort, n = 8 (25 patients were enrolled in 1.6 mg/kg q2w cohort). EGFR, epidermal growth factor receptor; MU, mutated; NSCLC, non–small cell lung cancer; NSQ, nonsquamous; OE, overexpression; q2w, once every 2 weeks; WT, wildtype.
TABLE 1.
Baseline Demographics and Disease Characteristics of Patients With c-Met Protein–Overexpressing Nonsquamous EGFR-Wildtype NSCLC
| Characteristic | c-Met High (n = 78) | c-Met Intermediate (n = 83) | c-Met OE Total (N = 161)a |
|---|---|---|---|
| Age, years, median (range) | 64.0 (38-83) | 66.0 (38-82) | 64.0 (33-83) |
| Sex, No. (%) | |||
| Male | 58 (74.4) | 53 (63.9) | 111 (68.9) |
| Female | 20 (25.6) | 30 (36.1) | 50 (31.1) |
| Race, No. (%) | |||
| White | 51 (65.4) | 59 (71.1) | 110 (68.3) |
| Black or African American | 1 (1.3) | 2 (2.4) | 3 (1.9) |
| Asian | 26 (33.3) | 22 (26.5) | 48 (29.8) |
| Region, No. (%) | |||
| North America | 9 (11.5) | 19 (22.9) | 28 (17.4) |
| Asia | 25 (32.1) | 19 (22.9) | 44 (27.3) |
| Europe | 29 (37.2) | 22 (26.5) | 51 (31.7) |
| Rest of world | 15 (19.2) | 23 (27.7) | 38 (23.6) |
| Tobacco use, No. (%) | |||
| Current | 10 (12.8) | 15 (18.1) | 25 (15.5) |
| Former | 54 (69.2) | 47 (56.6) | 101 (62.7) |
| Never | 14 (17.9) | 21 (25.3) | 35 (21.7) |
| Stage IV at study entry, No. (%) | 77 (98.7) | 81 (97.6) | 158 (98.1) |
| Brain metastasis, No. (%) | 14 (17.9) | 19 (22.9) | 33 (20.5) |
| ECOG performance status, No. (%) | |||
| 0 | 20 (25.6) | 27 (32.5) | 47 (29.2) |
| 1 | 57 (73.1) | 56 (67.5) | 113 (70.2) |
| 2 | 1 (1.3) | 0 | 1 (0.6) |
| No. of previous systemic cancer therapies, median (range) | 1 (1-3) | 1 (1-3) | 1 (1-3) |
| Type of previous systemic cancer therapies, n (%) | |||
| Platinum-based | 75 (96.2) | 82 (98.9) | 157 (97.5) |
| Immune checkpoint inhibitor–based | 66 (84.6) | 66 (79.5) | 132 (82.0) |
| Targeted therapyb,c | 4 (5.1) | 8 (9.6) | 12 (7.5) |
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Abbreviations: ECOG, Eastern Cooperative Oncology Group; EGFR, epidermal growth factor receptor; NSCLC, non–small cell lung cancer; OE, overexpressing.
aThe efficacy analysis set excludes four patients who did not have c-Met protein overexpression and seven patients in the China extension cohort who did not have adequate follow-up time. The four patients who did not have c-Met protein overexpression were enrolled either on the basis of MET amplification, which was allowed in earlier versions of the protocol, or because of cohort assignment errors during stage I.
bThe previous targeted therapies were crizotinib for four patients; alectinib, capmatinib, ceritinib, gefitinib, lapatinib + trastuzumab, lorlatinib, repotrectinib, sotorasib, tepotinib, trastuzumab deruxtecan, and glumetinib for one patient each.
cAlterations in genes other than EGFR were allowed, although available site-reported data on other alterations were limited and indicated alterations in a minority of patients.
At data cutoff (September 28, 2023), 159 (92.4%) of 172 patients with nonsquamous EGFR-wildtype NSCLC had discontinued study drug; the most common primary reasons were progressive disease per RECIST v1.1 (47.7%) and AEs (27.9%). The median duration of Teliso-V exposure was 19.7 weeks (range, 0.1-104), and 35 (20.3%) of 172 patients received ≥20 doses of Teliso-V. In total, 66 patients (41.0%) received ≥1 poststudy systemic therapy; most common were microtubule inhibitors (32 patients, 19.9%), targeted therapies (17 patients, 10.6%), and platinum-based chemotherapy (16 patients, 9.9%).
Efficacy
The nonsquamous EGFR-wildtype NSCLC cohort met protocol-specified criteria for expansion at Interim Analysis 3 (Appendix 1). The squamous and nonsquamous EGFR-mutant cohorts met protocol-specified criteria for futility at Interim Analyses 3 and 4, respectively (Appendix 1); ORRs for each cohort were 10.7% (95% CI, 2.3 to 28.2) and 11.4% (95% CI, 3.8 to 24.6), respectively. Detailed efficacy data for the squamous and nonsquamous EGFR-mutant cohorts are shown in Appendix Table AA33 and Appendix Figs AA11 and AA22.
At the primary analysis, among patients with c-Met protein–overexpressing, nonsquamous EGFR-wildtype NSCLC, ORR per ICR was 34.6% (95% CI, 24.2 to 46.2) for c-Met high, 22.9% (95% CI, 14.4 to 33.4) for c-Met intermediate, and 28.6% (95% CI, 21.7 to 36.2) for c-Met overexpression total (Table (Table2).2). ORR per investigator assessment was similar (Appendix Table AA4).4). Most patients exhibited reduction in tumor size (Fig (Fig3A).3A). The median time to onset of response per ICR was 1.41 months (range, 1.0-7.4) for c-Met overexpression total. The median DOR was 9.0 months (95% CI, 4.2 to 13.0) for c-Met high, 7.2 months (95% CI, 5.3 to 11.5) for c-Met intermediate, and 8.3 months (95% CI, 5.6 to 11.3) for c-Met overexpression total; the proportion of responders with response ≥6 months was 63.0%, 47.4%, and 56.5%, respectively (Fig (Fig3B).3B). The median PFS per ICR was 5.5 months (95% CI, 4.1 to 8.3) for c-Met high, 6.0 months (95% CI, 4.5 to 8.1) for c-Met intermediate, and 5.7 months (95% CI, 4.6 to 6.9) for c-Met overexpression total (Fig (Fig3C).3C). The median follow-up time was 20.2 months for c-Met high, 18.9 months for c-Met intermediate, and 19.3 months for c-Met overexpression total; the median OS was 14.6 months (95% CI, 9.2 to 25.6), 14.2 months (95% CI, 9.6 to 16.6), and 14.5 months (95% CI, 9.9 to 16.6), respectively (Fig (Fig33D).
TABLE 2.
Efficacy Summary in Patients With c-Met Protein–Overexpressing Nonsquamous EGFR-Wildtype NSCLC
| Outcome | c-Met High (n = 78) | c-Met Intermediate (n = 83) | c-Met OE Total (N = 161) |
|---|---|---|---|
| ORR,a % (95% CI) | 34.6 (24.2 to 46.2) | 22.9 (14.4 to 33.4) | 28.6 (21.7 to 36.2) |
| DCR,a % (95% CI) | 60.3 (48.5 to 71.2) | 57.8 (46.5 to 68.6) | 59.0 (51.0 to 66.7) |
| DOR,a months, median (95% CI) | 9.0 (4.2 to 13.0) | 7.2 (5.3 to 11.5) | 8.3 (5.6 to 11.3) |
| DOR ≥6 months,a n/no. of responders (%) | 17/27 (63.0) | 9/19 (47.4) | 26/46 (56.5) |
| PFS,a median, months (95% CI) | 5.5 (4.1 to 8.3) | 6.0 (4.5 to 8.1) | 5.7 (4.6 to 6.9) |
| 6-month PFS,a,b % (95% CI) | 45.8 (33.8 to 57.1) | 50.1 (37.9 to 61.1) | 48.0 (39.5 to 56.1) |
| OS, months, median (95% CI) | 14.6 (9.2 to 25.6) | 14.2 (9.6 to 16.6) | 14.5 (9.9 to 16.6) |
| 12-month OS,b % (95% CI) | 57.0 (45.0 to 67.4) | 55.0 (43.5 to 65.2) | 56.0 (47.7 to 63.4) |
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Abbreviations: DCR, disease control rate; DOR, duration of response; EGFR, epidermal growth factor receptor; NE, not estimable; NSCLC, non–small cell lung cancer; OE, overexpressing; ORR, overall response rate; OS, overall survival; PFS, progression-free survival.
aPer independent central review.
bEstimated using the Kaplan-Meier method.
FIG 3.
(A) Waterfall plot showing best reductions in target lesionsa; (B) time to response and duration of response for patients with a confirmed response; and (C) PFS and (D) OS for patients with c-Met protein–overexpressing, nonsquamous EGFR-wildtype NSCLC receiving 1.9 mg/kg Teliso-V. aOnly patients who had measurable disease at baseline and who had at least one measurable postbaseline assessment were included in the plot. DOR, duration of response; EGFR, epidermal growth factor receptor; H, c-Met high; I, c-Met intermediate; NE, not evaluable; NSCLC, non–small cell lung cancer; NSQ, nonsquamous; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease; Teliso-V, telisotuzumab vedotin; WT, wildtype.
Safety
Most patients with nonsquamous EGFR-wildtype NSCLC experienced a treatment-emergent AE (TEAE) of any grade (97.1%); 56.4% experienced a grade ≥3 TEAE. Any-grade treatment-related AEs (TRAEs) and grade ≥3 TRAEs occurred in 81.4% and 27.9% of patients, respectively. Most common any-grade TRAEs were peripheral sensory neuropathy (30.2%), peripheral edema (16.3%), fatigue (14.0%), decreased appetite (11.6%), increased ALT (11.0%), pneumonitis (10.5%), and hypoalbuminemia (10.5%; Table Table3).3). These events were mostly grade 1/2. Any-grade treatment-related neutropenia occurred in two patients (1.2%); no patients experienced grade ≥3 neutropenia or any-grade febrile neutropenia. TRAEs for the nonsquamous EGFR-mutant and squamous NSCLC cohorts are shown in Appendix Table AA55.
TABLE 3.
The Most Common Any-Grade and Grade ≥3 TRAEs Experienced by Patients in the c-Met Protein–Overexpressing Nonsquamous EGFR-Wildtype NSCLC Cohort
| Event | c-Met High (n = 84), No. (%) | c-Met Intermediate (n = 84), No. (%) | c-Met OE Total (N = 172), No. (%) | |||
|---|---|---|---|---|---|---|
| Any Grade | Grade ≥3 | Any Grade | Grade ≥3 | Any Grade | Grade ≥3 | |
| TEAE | 83 (98.8) | 50 (59.5) | 80 (95.2) | 45 (53.6) | 167 (97.1) | 97 (56.4) |
| TRAE | 68 (81.0) | 25 (29.8) | 69 (82.1) | 23 (27.4) | 140 (81.4) | 48 (27.9) |
| TRAEs occurring in >5% of patients in the NSQ EGFR WT NSCLC population | ||||||
| Peripheral sensory neuropathy | 24 (28.6) | 5 (6.0) | 27 (32.1) | 7 (8.3) | 52 (30.2) | 12 (7.0) |
| Peripheral edema | 17 (20.2) | 2 (2.4) | 11 (13.1) | 1 (1.2) | 28 (16.3) | 3 (1.7) |
| Fatigue | 11 (13.1) | 3 (3.6) | 12 (14.3) | 1 (1.2) | 24 (14.0) | 4 (2.3) |
| Decreased appetite | 7 (8.3) | 0 | 13 (15.5) | 1 (1.2) | 20 (11.6) | 1 (0.6) |
| Increased alanine aminotransferase | 8 (9.5) | 2 (2.4) | 11 (13.1) | 4 (4.8) | 19 (11.0) | 6 (3.5) |
| Pneumonitisa | 11 (13.1) | 3 (3.6) | 7 (8.3) | 2 (2.4) | 18 (10.5) | 5 (2.9) |
| Hypoalbuminemia | 10 (11.9) | 0 | 8 (9.5) | 0 | 18 (10.5) | 0 |
| Nausea | 6 (7.1) | 0 | 11 (13.1) | 0 | 17 (9.9) | 0 |
| Vision blurred | 11 (13.1) | 1 (1.2) | 5 (6.0) | 1 (1.2) | 16 (9.3) | 2 (1.2) |
| Increased aspartate aminotransferase | 7 (8.3) | 0 | 9 (10.7) | 0 | 16 (9.3) | 0 |
| Asthenia | 4 (4.8) | 1 (1.2) | 9 (10.7) | 0 | 13 (7.6) | 1 (0.6) |
| Anemia | 7 (8.3) | 1 (1.2) | 2 (2.4) | 0 | 10 (5.8) | 1 (0.6) |
| Increased gamma-glutamyltransferase | 5 (6.0) | 1 (1.2) | 5 (6.0) | 0 | 10 (5.8) | 1 (0.6) |
| Keratitis | 5 (6.0) | 0 | 5 (6.0) | 0 | 10 (5.8) | 0 |
| Peripheral neuropathy | 6 (7.1) | 1 (1.2) | 3 (3.6) | 0 | 9 (5.2) | 1 (0.6) |
| Decreased weight | 4 (4.8) | 0 | 4 (4.8) | 0 | 9 (5.2) | 0 |
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NOTE. Considered possibly related to study drug by the investigator. TRAEs are shown by the MedDRA Preferred Term according to investigative site reporting.
Abbreviations: EGFR, epidermal growth factor receptor; ILD, interstitial lung disease; NSCLC, non–small cell lung cancer; NSQ, nonsquamous; OE, overexpressing; TEAE, treatment-emergent adverse event; TRAE, treatment-related adverse event; WT, wildtype.
aPneumonitis events shown are those with a MedDRA preferred term of pneumonitis according to the investigative site reporting. In addition, TRAEs with a preferred term of ILD according to investigative site reporting were noted in 4 (2.3%) patients with c-Met OE total (c-Met high, n = 2 [2.4%]; c-Met intermediate, n = 2 [2.4%]). Investigative site-reported events of potential ILD, including the terms of pneumonitis and ILD, were also adjudicated as ILD or not ILD by an independent committee. Adjudicated events of ILD occurred in 17 patients (9.9%); nine had events adjudicated as grade ≥3 (5.2%), of which three were grade 5.
TRAEs leading to treatment discontinuation were reported in 21.5% of patients with nonsquamous EGFR-wildtype NSCLC; most common were pneumonitis (7.6%), peripheral sensory neuropathy (7.0%), peripheral sensorimotor neuropathy (2.3%), and ILD (1.2%). The median time to onset was 170 days (range 1-519). The median time to onset of ILD (Standardised MedDRA Queries [SMQ]; broad) events resulting in treatment discontinuation was 48 days (range, 7-344); the median time to onset of peripheral neuropathy (SMQ narrow) events leading to discontinuation was 222.5 days (range, 57-519). Ocular toxicities (eg, keratitis and vision blurred) did not lead to discontinuation in any patient. Two patients (1.2%) had grade 5 AEs that were considered possibly related to Teliso-V; these were ILD and respiratory failure.
Adjudicated events of ILD occurred in 17 patients (9.9%; grade 1, n = 3 [1.7%]; grade 2, n = 5 [2.9%]; grade 3, n = 5 [2.9%]; grade 4, n = 1 [0.6%]; grade 5, n = 3 [1.7%]). Of the three grade 5 events, one death was considered related to ILD per the investigator (two were considered related to progressive disease per the investigator).
DISCUSSION
The phase II LUMINOSITY study aimed to determine which c-Met protein–overexpressing NSCLC patient population would most benefit from treatment with Teliso-V and to further evaluate the efficacy within those patients. The nonsquamous EGFR-wildtype NSCLC cohort met criteria for expansion, whereas the squamous and nonsquamous EGFR-mutant cohorts met protocol-specified criteria for futility. Lower efficacy may be observed in the squamous cohort because of the lower cutoff used for c-Met overexpression versus the nonsquamous cohort. For patients with nonsquamous EGFR-mutant NSCLC, it is notable that higher response rates have been reported in a comparable population of patients treated with Teliso-V plus osimertinib, and preclinical data suggest an interaction between the mechanisms of action for Teliso-V and osimertinib may improve response to the combination.17
The highest ORR was observed among patients with c-Met protein–overexpressing, nonsquamous EGFR-wildtype NSCLC, and ORR was enriched among patients with c-Met high overexpressing tumors. The observed trend toward higher ORR with higher level of c-Met protein overexpression contrasts with studies evaluating ADCs targeting trophoblast antigen 2 (TROP2) in NSCLC, where TROP2 expression was not predictive of response.18,19 Although ORR was increased in the c-Met high population, DCR, PFS, and OS were comparable between c-Met high, c-Met intermediate, and c-Met total overexpression, consistent with the reduction in tumor burden observed in most patients and indicating Teliso-V was efficacious in patients with c-Met protein–overexpressing tumors regardless of the level of expression.
The ORRs in patients with c-Met protein–overexpressing, nonsquamous EGFR-wildtype NSCLC observed with Teliso-V compare favorably with those for standard of care in the second-line-and-beyond setting, which are generally limited to single-agent chemotherapy, such as docetaxel with or without an antiangiogenic agent. The phase III REVEL trial evaluating docetaxel with or without ramucirumab enrolled patients with NSCLC who had disease progression on platinum-based therapy. In a subgroup analysis in patients with nonsquamous disease, ORRs per investigator were 21.9% (95% CI, 18.3 to 26.0) for docetaxel plus ramucirumab and 14.5% (95% CI, 11.4 to 18.2) for docetaxel plus placebo.20 The phase III LUME-Lung 1 study evaluated docetaxel with or without nintedanib in patients whose NSCLC progressed after first-line chemotherapy. In those patients with adenocarcinoma, ORR per ICR was 4.7% for docetaxel plus nintedanib and 3.6% for docetaxel plus placebo.21 In LUMINOSITY, Teliso-V was evaluated in a similar population of patients, with a median of one previous treatment line, and 98% of patients having received previous platinum.
The REVEL and LUME-Lung 1 studies did not report median DOR. However, other published data indicate that the observed median DOR in patients with c-Met protein–overexpressing, nonsquamous EGFR-wildtype NSCLC treated with Teliso-V exceeds that reported for docetaxel in other phase III studies. The phase III CheckMate 057 study included a docetaxel treatment arm and enrolled patients with advanced/metastatic nonsquamous NSCLC who received previous platinum therapy, comparable with the nonsquamous, predominantly metastatic, and previous platinum-treated NSCLC population in our study. In contrast to the LUMINOSITY study, patients in CheckMate 057 were naïve to immune checkpoint inhibitors, and 13% of those in the docetaxel arm had EGFR mutations. The reported median ORR with docetaxel was 12% (95% CI, 9 to 17) and the median DOR was 5.6 months (95% CI, 4.4 to 6.9).22,23 Given c-Met expression is associated with worse outcomes in NSCLC,11 whether these historical data are directly comparable with the patient population in LUMINOSITY remains to be determined within a randomized trial.
The AE profile among patients with nonsquamous EGFR-wildtype NSCLC observed with Teliso-V was generally consistent with reports of MMAE ADCs and MET-targeting agents. Peripheral sensory neuropathy was the most common AE and has been associated with MMAE ADCs.24 These events were predominantly low grade, and patients were generally able to continue treatment after onset by dose reductions and interruptions. Ocular toxicities have also been reported with MMAE ADCs,24 and events including keratitis and blurred vision were reported with Teliso-V. These were rarely grade ≥3, and no events of keratitis or blurred vision led to discontinuation. Peripheral edema and hypoalbuminemia are frequently reported with MET inhibitors.7,8 These events were also observed with Teliso-V, although any-grade TRAEs occurred in a minority of the patients (peripheral edema, 16.3%; hypoalbuminemia, 10.5%) and were predominantly low grade. ILD cases, including grade 5 events, were also observed. Most patients with nonsquamous EGFR-wildtype NSCLC in the current study received previous immune checkpoint inhibitor, and a previous report has suggested that patients with previous immune checkpoint inhibitor have a greater likelihood of ILD during subsequent therapy.25 ILD, including fatal cases, has been reported with other NSCLC agents, including ADCs trastuzumab deruxtecan26 and datopotamab deruxtecan.27 Hematologic toxicity has also been reported for MMAE ADCs24 but was generally uncommon with Teliso-V, with related grade ≥3 anemia reported in one patient, no grade ≥3 related neutropenia, and no febrile neutropenia reported for the nonsquamous EGFR-wildtype NSCLC population.
The frequency of TRAEs leading to discontinuation was 21.5%. The TRAEs leading to discontinuation were most commonly peripheral neuropathy or ILD/pneumonitis. Per protocol, drug discontinuation was recommended for pneumonitis events of grade ≥2. Peripheral neuropathy is a known cumulative toxicity associated with MMAE ADCs.28 The median time to onset of a TRAE leading to discontinuation was 170 days and the median time to onset of peripheral neuropathy TRAEs leading to discontinuation was 222.5 days, suggesting many discontinuations were among patients who remained on drug for an extended time. Teliso-V was administered for ≥20 cycles in 20.3% of patients, indicating tolerability of the treatment.
This phase II trial is limited by the lack of a comparator arm. The ongoing global, randomized phase III study TeliMET NSCLC-01 (ClinicalTrials.gov identifier: NCT04928846) compares Teliso-V monotherapy with docetaxel in patients with previously treated locally advanced/metastatic, c-Met protein–overexpressing, nonsquamous EGFR-wildtype NSCLC. Given the potential overlap of some genomic markers of MET activation with c-Met protein overexpression, retrospective analyses of the current study data on available tissue or blood for these markers will be of interest.
Currently, no therapies specifically for patients with c-Met protein–overexpressing NSCLC are available. In LUMINOSITY, Teliso-V was associated with durable responses in c-Met protein–overexpressing nonsquamous EGFR-wildtype NSCLC, with ORRs enriched in patients with high c-Met expression.
ACKNOWLEDGMENT
AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the manuscript. All authors had access to relevant data and participated in the drafting, review, and approval of this manuscript. No honoraria or payments were made for authorship.
AbbVie and the authors thank all the trial investigators and the patients who participated in this clinical trial. Medical writing support was provided by Joanne Franklin, PhD, CMPP, from Aptitude Health, The Hague, the Netherlands, and funded by AbbVie.
APPENDIX: Supplementary Methods and Results
Prespecified Criteria for Futility Analysis
The decision to stop the enrollment of a group for futility in stage I or move a group to the expansion cohort in stage II was based on the estimated posterior probabilities of success by comparing it with the lower and upper decision thresholds. The posterior probability of success was defined as the posterior probability of the overall response rate exceeding 25%. The lower decision threshold was defined as 10% and the upper decision threshold was defined as 70%. The above analysis was also performed at the cohort level. For each interim analysis, decision making started when at least 10 efficacy-evaluable patients were enrolled under one group or at least 15 efficacy-evaluable patients were enrolled in one cohort (ie, nonsquamous EGFR-wildtype; nonsquamous EGFR-mutated). When the posterior probability of success for a specific group exceeding 25% fell below 0.10, the group was considered futile. Conversely, if the same posterior probability estimate was high (exceeded 0.70), then that group was graduated to the stage II expansion.
Interim Analysis Decision-Making Results
At Interim Analysis 3, the EGFR-wildtype nonsquamous cohort was determined to advance to stage II on the basis of the posterior probability of success of 91% and the squamous cohort was stopped for futility on the basis of the posterior probability of success of 9.3%. The EGFR-mutant nonsquamous cohort continued enrolling until Interim Analysis 4 when the futility criteria were met (posterior probability of success of 1.6% for the EGFR-mutant nonsquamous cohort and 2.9% for the EGFR-mutant nonsquamous c-Met intermediate group; the EGFR-mutant nonsquamous c-Met high group met the enrollment cap of 30 patients with a posterior probability of success of 14.5%).
Changes in MET Over Time
In the EGFR-wildtype nonsquamous non–small cell lung cancer cohort, 28 paired tissues were available. Of these, 21 (75%) had the same MET status, 2 (7%) changed from positive to negative, and 5 (18%) changed from negative to positive. Collectively then, over 90% of the time, c-Met protein overexpression status was the same or higher in repeat biopsy.
FIG A1.
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(A) Waterfall plot showing best reductions in target lesions for patients with c-Met protein–overexpressing, squamous NSCLC receiving 1.9 mg/kg Teliso-Va; (B) progression-free survival for patients with c-Met protein–overexpressing, squamous NSCLC receiving 1.9 mg/kg Teliso-V; (C) OS for patients with c-Met protein–overexpressing, squamous NSCLC receiving 1.9 mg/kg Teliso-V. aOnly patients who had measurable disease at baseline and who had at least one measurable postbaseline assessment were included in this analysis. NSCLC, non–small cell lung cancer; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease; SQ, squamous; Teliso-V, telisotuzumab vedotin.
FIG A2.
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(A) Waterfall plot showing best reductions in target lesionsa for patients with c-Met protein–overexpressing, nonsquamous EGFR-mutant NSCLC receiving 1.9 mg/kg Teliso-V; (B) progression-free survival for patients with c-Met protein–overexpressing, nonsquamous EGFR-mutant NSCLC receiving 1.9 mg/kg Teliso-V; (C) OS for patients with c-Met protein–overexpressing, nonsquamous EGFR-mutant NSCLC receiving 1.9 mg/kg Teliso-V. aOnly patients who had measurable disease at baseline and who had at least one measurable postbaseline assessment were included in this analysis. EGFR, epidermal growth factor receptor; H, c-Met high; I, c-Met intermediate; MU, mutant; NSCLC, non–small cell lung cancer; NSQ, nonsquamous; OS, overall survival; PD, progressive disease; PR, partial response; SD, stable disease; Teliso-V, telisotuzumab vedotin.
TABLE A1.
Eligibility Criteria
| Inclusion Criteria | Exclusion Criteria |
|---|---|
| Adults age ≥18 years | Adenosquamous histology |
| c-Met protein overexpression as assessed by sponsor-designated IHC criteria | Received previous c-Met–targeted therapies |
| Adequate bone marrow, renal, and hepatic function | History of other malignancies except Malignancy treated with curative intent and with no known active disease present for ≥2 years before the first dose of Teliso-V and considered low risk for recurrence by investigator Adequately treated nonmelanoma skin cancer or lentigo maligna without evidence of disease Adequately treated carcinoma in situ without current evidence of disease |
| Histologically documented nonsquamous NSCLC with known EGFR mutation (wildtype or mutant) or histologically documented squamous cell NSCLC | History of ILD or pneumonitis that required treatment with systemic steroids |
| Locally advanced/metastatic NSCLC | Evidence of pulmonary fibrosis on screening imaging assessment or any history of pneumonitis or ILD within 3 months of the planned first dose of Teliso-V |
| ECOG performance status 0 or 1 | Unresolved clinically significant adverse events grade ≥2 from previous anticancer therapy, except for alopecia or anemia |
| Measurable disease per RECIST v1.1 | Major surgery within 21 days before the first dose of Teliso-V |
| Received no more than two lines of previous systemic therapy, including no more than one line of systemic cytotoxic chemotherapy; multiple lines of TKIs targeting the same tyrosine kinase count as one line of therapy | Received radiation therapy to the lung <6 months before the first dose of Teliso-V |
| Progression on systemic cytotoxic chemotherapy (or are ineligible for systemic cytotoxic chemotherapy) and an immune checkpoint inhibitor (as monotherapy or in combination with systemic cytotoxic chemotherapy, or ineligible for an immune checkpoint inhibitor), and previous anticancer therapies targeting driver gene alterations (if applicable) | A clinically significant condition(s) including, but not limited to, the following: Grade ≥2 edema or lymphedema Grade ≥2 ascites or pleural effusion Grade ≥2 or history of grade ≥3 peripheral neuropathy Active uncontrolled bacterial or viral infection New York Heart Association Class ≥III congestive heart failure Unstable angina pectoris or cardiac arrhythmia |
| Patients with CNS metastasis if they have received definitive therapy and There is no evidence of progression ≥2 weeks after definitive therapy They are asymptomatic and off systemic steroids and anticonvulsants for at least 2 weeks before the first dose of Teliso-V | History of major immunologic reaction to any immunoglobulin (IgG)-containing agent |
| Negative serum pregnancy test and no breastfeeding | Known active severe COVID-19 disease |
| Male and female patients must be using birth control methods | Received any live vaccine within 30 days of first dose of Teliso-V |
| Received any of the following in the noted time intervals: Within 1 week (7 days): strong cytochrome P450 3A4 (CYP3A4) inhibitors Within 2 weeks (14 days): radiation not involving the thoracic cavity Within 4 weeks (28 days): systemic cytotoxic chemotherapy; small-molecule targeted; monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or T-cell or other cell-based therapies |
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Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; IHC, immunohistochemistry; ILD, interstitial lung disease; NSCLC, non–small cell lung cancer; Teliso-V, telisotuzumab vedotin; TKI, tyrosine kinase inhibitor.
TABLE A2.
Baseline Demographics and Disease Characteristics of Patients With Nonsquamous EGFR-Mutated NSCLC and Squamous NSCLC
| Characteristic | NSQ EGFR MUa NSCLC (n = 44)b,c | SQ NSCLC (n = 28) | Total Study Population (N = 233) |
|---|---|---|---|
| Age, years, median (range) | 62 (36-81) | 66 (45-76) | 64 (33-83) |
| Sex, No. (%) | |||
| Male | 19 (43.2) | 17 (60.7) | 147 (63.1) |
| Female | 25 (56.8) | 11 (39.3) | 86 (36.9) |
| Race, No. (%) | |||
| White | 17 (38.6) | 26 (29.9) | 153 (65.7) |
| Black or African American | 0 | 0 | 3 (1.3) |
| Asian | 27 (61.4) | 2 (7.1) | 77 (33.0) |
| Region, No. (%) | |||
| North America | 8 (18.2) | 6 (21.4) | 42 (18.0) |
| Asia | 22 (50.0) | 2 (7.1) | 68 (29.2) |
| Europe | 10 (22.7) | 6 (21.4) | 67 (28.8) |
| Rest of world | 4 (9.1) | 14 (50.0) | 56 (24.0) |
| Tobacco use, No. (%) | |||
| Current | 0 | 6 (21.4) | 31 (13.3) |
| Former | 17 (38.6) | 20 (71.4) | 138 (59.2) |
| Never | 27 (61.4) | 2 (7.1) | 64 (27.5) |
| Stage IV at study entry, No. (%) | 43 (97.7) | 20 (71.4) | 221 (94.8) |
| Brain metastasis, No. (%) | 13 (29.5) | 1 (3.6) | 47 (20.2) |
| ECOG performance status, No. (%) | |||
| 0 | 15 (34.1) | 4 (14.3) | 66 (28.3) |
| 1 | 29 (65.9) | 24 (85.7) | 166 (71.2) |
| 2 | 0 | 0 | 1 (0.4) |
| No. of previous systemic cancer therapies, median (range) | 2 (1-4) | 1 (1-4) | 1 (1-4) |
| Type of previous systemic cancer therapies, No. (%) | |||
| Platinum-based | 40 (90.9) | 28 (100) | 225 (96.6) |
| Immune checkpoint inhibitor–based | 8 (18.2) | 26 (92.9) | 166 (71.2) |
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Abbreviations: ECOG, Eastern Cooperative Oncology Group; EGFR, epidermal growth factor receptor; MU, mutated; NSCLC, non–small cell lung cancer; NSQ, nonsquamous; SQ, squamous; TKI, tyrosine kinase inhibitor.
aData on mutations were site-reported. The most common mutations were DEL 19 (n = 22), L858R (n = 17), and T790M (n = 12).
bOne patient in the NSQ EGFR MU NSCLC cohort did not overexpress c-Met.
cForty-three patients (97.7%) in the NSQ EGFR MU NSCLC cohort had previous EGFR TKI (first/second generation, 39 [88.6%]; third generation, 16 [36.4%]).
TABLE A3.
Efficacy Summary of Patients With c-Met Protein–Overexpressing Nonsquamous EGFR-Mutant NSCLC and Squamous Cell NSCLC
| Outcome | NSQ EGFR MU NSCLC | SQ NSCLC (N = 28) | ||
|---|---|---|---|---|
| c-Met High (n = 30) | c-Met Int (n = 14) | c-Met OE Total (N = 44) | ||
| ORR,a % [95% CI] | 5 (16.7) [5.6 to 34.7] | 0 [0.0 to 23.2] | 5 (11.4) [3.8 to 24.6] | 3 (10.7) [2.3 to 28.2] |
| DCR,a % [95% CI] | 46.7 [28.3 to 65.7] | 28.6 [8.4 to 58.1] | 40.9 [26.3 to 56.8] | 35.7 [18.6 to 55.9] |
| Median DOR,a months [95% CI] | 17.4 [3.0 to NE] | NE [NE to NE] | 17.4 [3.0 to NE] | 4.4 [3.0 to NE] |
| DOR ≥6 months,a n/no. of responders (%) | 2/5 (40) | 0 | 2/5 (40) | 0 |
| PFS,a months, median [95% CI] | 4.1 [2.8 to 5.7] | 4.0 [2.1 to 6.2] | 4.0 [3.0 to 5.6] | 3.2 [2.5 to 5.7] |
| 6-month PFSa,b, % [95% CI] | 31.7 [15.2 to 49.6] | 31.3 [8.1 to 58.5] | 31.5 [17.4 to 46.7] | 30.6 [13.8 to 49.2] |
| OS, months, median [95% CI] | 13.4 [8.9 to 19.3] | 21.4 [9.9 to 32.3] | 15.0 [10.6 to 21.4] | 5.9 [4.5 to 13.0] |
| 12-month OSb, % [95% CI] | 61.1 [40.8 to 76.3] | 68.6 [35.9 to 87.0] | 63.7 [47.1 to 76.3] | 37.6 [20.0 to 55.2] |
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Abbreviations: DOR, duration of response; EGFR, epidermal growth factor receptor; MU, mutated; NE, not evaluable; NSCLC, non–small cell lung cancer; NSQ, nonsquamous; OE, overexpressing; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; SQ, squamous.
aPer independent central review.
bEstimated by Kaplan-Meier method.
TABLE A4.
Investigator-Assessed Overall Response Rates of Patients With c-Met Protein–Overexpressing Nonsquamous EGFR-Wildtype NSCLC
| Response Rate | c-Met High (n = 78) | c-Met Intermediate (n = 83) | NSQ EGFR WT NSCLC Total (N = 161) |
|---|---|---|---|
| ORR (CR + PR) [95% CI] | 29 (37.2) [26.5 to 48.9] | 18 (21.7) [13.4 to 32.1] | 47 (29.2) [22.3 to 36.9] |
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Abbreviations: CR, complete response; EGFR, epidermal growth factor receptor; NSCLC, non–small cell lung cancer; NSQ, nonsquamous; ORR, overall response rate; PR, partial response; WT, wildtype.
TABLE A5.
Most Common Any-Grade and Grade ≥3 TRAEs Experienced by Patients in All Study Cohorts
| Event | NSQ EGFR WT NSCLC Total (n = 172), No. (%) | NSQ EGFR MU NSCLC Total (n = 45), No. (%) | SQ NSCLC Total (n = 28), No. (%) | Overall Total (N = 245), No. (%) | ||||
|---|---|---|---|---|---|---|---|---|
| Any Grade | Grade ≥3 | Any Grade | Grade ≥3 | Any Grade | Grade ≥3 | Any Grade | Grade ≥3 | |
| TEAE | 167 (97.1) | 97 (56.4) | 45 (100) | 21 (46.7) | 28 (100) | 18 (64.3) | 240 (98.0) | 136 (55.5) |
| TRAE | 140 (81.4) | 48 (27.9) | 41 (91.1) | 11 (24.4) | 19 (67.9) | 9 (32.1) | 200 (81.6) | 68 (27.8) |
| TRAEs occurring in >5% of patients in the NSQ EGFR WT NSCLC | ||||||||
| Peripheral sensory neuropathy | 52 (30.2) | 12 (7.0) | 11 (24.4) | 1 (2.2) | 2 (7.1) | 1 (3.6) | 65 (26.5) | 14 (5.7) |
| Edema peripheral | 28 (16.3) | 3 (1.7) | 8 (17.8) | 0 | 2 (7.1) | 0 | 38 (15.5) | 3 (1.2) |
| Fatigue | 24 (14.0) | 4 (2.3) | 4 (8.9) | 0 | 4 (14.3) | 3 (10.7) | 32 (13.1) | 7 (2.9) |
| Decreased appetite | 20 (11.6) | 1 (0.6) | 8 (17.8) | 0 | 1 (3.6) | 0 | 29 (11.8) | 1 (0.4) |
| Increased ALT | 19 (11.0) | 6 (3.5) | 4 (8.9) | 1 (2.2) | 2 (7.1) | 0 | 25 (10.2) | 7 (2.9) |
| Pneumonitis | 18 (10.5) | 5 (2.9) | 1 (2.2) | 1 (2.2) | 2 (7.1) | 1 (3.6) | 21 (8.6) | 7 (2.9) |
| Hypoalbuminemia | 18 (10.5) | 0 | 5 (11.1) | 1 (2.2) | 5 (17.9) | 0 | 28 (11.4) | 1 (0.4) |
| Nausea | 17 (9.9) | 0 | 10 (22.2) | 0 | 3 (10.7) | 0 | 30 (12.2) | 0 |
| Blurred vision | 16 (9.3) | 2 (1.2) | 9 (20.0) | 0 | 2 (7.1) | 0 | 27 (11.0) | 2 (0.8) |
| Increased AST | 16 (9.3) | 0 | 5 (11.1) | 0 | 1 (3.6) | 0 | 22 (9.0) | 0 |
| Asthenia | 13 (7.6) | 1 (0.6) | 6 (13.3) | 1 (2.2) | 1 (3.6) | 1 (3.6) | 20 (8.2) | 3 (1.2) |
| Anemia | 10 (5.8) | 1 (0.6) | 4 (8.9) | 1 (2.2) | 3 (10.7) | 0 | 17 (6.9) | 2 (0.8) |
| Increased gamma-glutamyltransferase | 10 (5.8) | 1 (0.6) | 3 (6.7) | 0 | 3 (10.7) | 1 (3.6) | 16 (6.5) | 2 (0.8) |
| Keratitis | 10 (5.8) | 0 | 8 (17.8) | 0 | 2 (7.1) | 0 | 20 (8.2) | 0 |
| Peripheral neuropathy | 9 (5.2) | 1 (0.6) | 1 (2.2) | 0 | 0 | 0 | 10 (4.1) | 1 (0.4) |
| Decreased weight | 9 (5.2) | 0 | 0 | 0 | 1 (3.6) | 0 | 10 (4.1) | 0 |
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Abbreviations: EGFR, epidermal growth factor receptor; MU, mutated; NSCLC, non–small cell lung cancer; NSQ, nonsquamous; SQ, squamous; TEAE, treatment-emergent adverse event; TRAE, treatment-related adverse event; WT, wildtype.
Notes
D. Ross Camidge
Honoraria: Roche, Takeda, AstraZeneca, Daiichi Sankyo, Bio-Thera, Ribon Therapeutics, AbbVie, Apollomics, Elevation Oncology, EMD Serono, Helsinn Therapeutics, Lilly, Nuvalent, Inc, Seagen, Kestrel Labs, Amgen Astellas BioPharma, Janssen, OnKure, Mersana, Sanofi, Anheart Therapeutics, BeiGene, Hengrui Pharmaceutical, Puma Biotechnology, Turning Point Therapeutics, BeiGene, Dizal Pharma, Hummingbird, Mirati Therapeutics, Nalo Therapeutics
Research Funding: Inivata (Inst)
Jair Bar
Stock and Other Ownership Interests: Causalis
Consulting or Advisory Role: Pfizer, Bristol Myers Squibb, AstraZeneca, AbbVie, MSD, Takeda, Bayer, Novartis, Roche, Merck Serono, BeiGene
Research Funding: AstraZeneca/MedImmune (Inst), MSD (Inst), Pfizer (Inst), Roche (Inst), AbbVie (Inst), Novartis (Inst), Takeda (Inst), Oncohost (Inst), Immunai (Inst)
Hidehito Horinouchi
Honoraria: Lilly, Bristol Myers Squibb Japan, Kyowa Hakko Kirin, Chugai Pharma, AstraZeneca, MSD Oncology, AbbVie, Amgen, Taiho Pharmaceutical, Ono Pharmaceutical, Merck Serono, Pfizer, Daiichi Sankyo
Consulting or Advisory Role: AstraZeneca, Chugai Pharma, AbbVie, Daiichi Sankyo, Yuhan, Novocure, Seagen
Research Funding: Taiho Pharmaceutical (Inst), Merck Serono (Inst), Novartis (Inst), MSD Oncology (Inst), Chugai Pharma (Inst), Ono Pharmaceutical (Inst), A2 Healthcare (Inst), Daiichi Sankyo (Inst), BMKK (Inst), AbbVie (Inst), AstraZeneca (Inst), Amgen (Inst), Boehringer Ingelheim (Inst)
Jonathan Goldman
Consulting or Advisory Role: AstraZeneca, AbbVie, Genentech, Regeneron, Jazz Pharmaceuticals, Gritstone Bio, Gilead Sciences, Daiichi Sankyo/AstraZeneca, Summit Biomedical
Research Funding: Lilly (Inst), Genentech/Roche (Inst), Bristol Myers Squibb (Inst), AstraZeneca/MedImmune (Inst), AbbVie (Inst), Advaxis (Inst), Pfizer (Inst), Summit Biomedical (Inst), EMD Serono (Inst), Amgen (Inst), Lyell Immunopharma (Inst), Genmab (Inst), Astellas Pharma (Inst), GlaxoSmithKline (Inst), Janssen (Inst)
Open Payments Link:https://openpaymentsdata.cms.gov/physician/124819
Fedor Moiseenko
Honoraria: AstraZeneca, Takeda, Sanofi/Aventis, Pfizer/EMD Serono, BioCad, Novartis, MSD Oncology, Merck, Roche, Bristol Myers Squibb, Boehringer Ingelheim, Lilly
Consulting or Advisory Role: Boehringer Ingelheim, AstraZeneca, Pfizer, Sanofi
Speakers' Bureau: Takeda, Roche, Bristol Myers Squibb, Boehringer Ingelheim, Lilly
Research Funding: BioCad (Inst)
Travel, Accommodations, Expenses: Sanofi/Aventis, Bristol Myers Squibb, AstraZeneca, Boehringer Ingelheim, Boehringer Ingelheim
Other Relationship: Pfizer (Inst), AstraZeneca (Inst), Roche, Bristol Myers Squibb (Inst), MSD Oncology
Elena Filippova
Honoraria: Pfizer, Takeda, AbbVie
Speakers' Bureau: Pfizer
Irfan Cicin
Consulting or Advisory Role: Pfizer (Inst), MSD Oncology (Inst), Roche (Inst), Novartis/Ipsen (Inst), Lilly (Inst), Bristol Myers Squibb (Inst), SERVIER (Inst), Abdi Ibrahim (Inst), Nobelpharma (Inst), AbbVie (Inst), Teva, Janssen Oncology (Inst), Takeda (Inst), Gen (Inst), Astellas Pharma (Inst), Gilead Sciences (Inst)
Speakers' Bureau: Novartis (Inst), Roche (Inst), Bristol Myers Squibb (Inst), Pfizer (Inst), Abdi Ibrahim (Inst), Astellas Pharma, MSD (Inst), MSD (Inst), Gen (Inst), Teva (Inst)
Tudor Ciuleanu
Consulting or Advisory Role: Astellas Pharma, Janssen, Bristol Myers Squibb, Merck Serono, Amgen, Roche, Pfizer, Boehringer Ingelheim, Lilly, AstraZeneca, Merck Sharp & Dohme, Sanofi, Novartis, SERVIER, A&D Pharma, Accord Healthcare, MagnaPharm, Takeda
Travel, Accommodations, Expenses: Pfizer, Sanofi, Boehringer Ingelheim, Merck, Servier, Ipsen, Amgen, A&D Pharma, AstraZeneca, Roche/Genentech, Bristol Myers Squibb, MSD, Lilly, Janssen, Novartis, Astellas Pharma
Nathalie Daaboul
Consulting or Advisory Role: AstraZeneca Canada, Bristol Myers Squibb/Celgene, Merck, Pfizer, Roche, Takeda, Amgen, Taiho Oncology, Eisai
Penelope Bradbury
(OPTIONAL) Uncompensated Relationships: AbbVie
(OPTIONAL) Uncompensated Relationships: Bristol Myers Squibb
(OPTIONAL) Uncompensated Relationships: Mirati Therapeutics
(OPTIONAL) Uncompensated Relationships: Merck
(OPTIONAL) Uncompensated Relationships: Raptor Pharmaceuticals
Mor Moskovitz
Honoraria: MSD, BMSi, Roche, Takeda, AbbVie, AstraZeneca, Johnson & Johnson/Janssen
Consulting or Advisory Role: AstraZeneca, MSD Oncology, Takeda, Roche, Pfizer, JNJ, Novartis, Amgen
Travel, Accommodations, Expenses: Pfizer, MSD, Roche
Pascale Tomasini
Consulting or Advisory Role: AstraZeneca, Roche, Bristol Myers Squibb Foundation, Takeda, Amgen, Janssen
Travel, Accommodations, Expenses: Bristol Myers Squibb/Pfizer, AstraZeneca, Takeda
Alona Zer
Stock and Other Ownership Interests: Nixio
Honoraria: MSD, Roche, Bristol Myers Squibb, AstraZeneca, Takeda, Novartis
Consulting or Advisory Role: Lilly, Boehringer Ingelheim, Roche, MSD, Oncotest/Rhenium, Oncohost
Research Funding: Bristol Myers Squibb (Inst)
Travel, Accommodations, Expenses: AstraZeneca, MSD, Roche
Other Relationship: Beyond Air
Nicolas Girard
Employment: AstraZeneca
Consulting or Advisory Role: Roche, Lilly, AstraZeneca, Novartis, Pfizer, Bristol Myers Squibb, MSD, Takeda, Janssen, Sanofi, AMGEN, Gilead Sciences, BeiGene, AbbVie, Daiichi Sankyo/AstraZeneca, LEO Pharma, Ipsen
Research Funding: Roche (Inst), AstraZeneca (Inst), BMS (Inst), MSDAvenir (Inst)
Travel, Accommodations, Expenses: Roche, Janssen Oncology
Kristof Cuppens
Consulting or Advisory Role: Bristol Myers Squibb, MSD, AstraZeneca/MedImmune, Roche/Genentech, Janssen, Amgen
Research Funding: Bristol Myers Squibb (Inst), AstraZeneca/MedImmune
Expert Testimony: AstraZeneca, MSD
Travel, Accommodations, Expenses: Roche/Genentech, AstraZeneca, Janssen, MSD
Ji-Youn Han
Honoraria: AstraZeneca, Takeda, Novartis, Merck, Janssen, Pfizer, Yuhan
Consulting or Advisory Role: Novartis, Merck, Takeda, Janssen, Lantern Pharma, Amgen, AstraZeneca, Daiichi Sankyo/UCB Japan, Oncovix, AbbVie
Research Funding: Roche, Pfizer
Shobhit Baijal
Honoraria: AbbVie, Agilent, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb Foundation, Chugai Pharma, FoundationOne, Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Merck Serono, Merck Sharp & Dohme, Novartis, Pierre Fabre, Pfizer, Roche, SERVIER, Sanofi and Takeda, Daiichi Sankyo
Aaron S. Mansfield
Honoraria: Roche
Consulting or Advisory Role: Genentech (Inst), Bristol Myers Squibb (Inst), AbbVie (Inst), AstraZeneca (Inst), Janssen (Inst), BeiGene (Inst), Takeda (Inst), Genzyme (Inst), Gilead Sciences (Inst), Johnson & Johnson Global Services (Inst)
Speakers' Bureau: Chugai/Roche (Inst)
Research Funding: Novartis (Inst), Verily (Inst), Bristol Myers Squibb (Inst)
Travel, Accommodations, Expenses: AbbVie, Roche
Other Relationship: Mesothelioma Applied Research Foundation
Chih-Hsi Kuo
Honoraria: Boehringer Ingelheim, AstraZeneca, Roche, Pfizer, Lilly, Novartis, Ono Pharmaceutical, Chugai Pharma, Merck, Janssen Oncology, Takeda, Guardant Health AMEA
Consulting or Advisory Role: AstraZeneca, Boehringer Ingelheim, Lilly, Merck, Chugai Pharma, Takeda, Novartis, Guardant Health AMEA
Kazumi Nishino
Honoraria: Chugai Pharma, AstraZeneca Japan, Nippon Boehringer Ingelheim, Lilly Japan, Novartis, Merck, Pfizer, Janssen, Bristol Myers Squibb Japan, Nippon Kayaku
Consulting or Advisory Role: Pfizer, AstraZeneca, Lilly Japan
Research Funding: Ono Pharmaceutical (Inst), Taiho Pharmaceutical (Inst), MSD (Inst), Daiichi Sankyo/UCB Japan (Inst), AbbVie (Inst), Amgen (Inst), Eisai (Inst), Sanofi (Inst), Janssen (Inst), Novartis (Inst), Pfizer (Inst), Lilly Japan (Inst), Merck (Inst), Takeda (Inst), Chugai Pharma (Inst), Merus (Inst), Bayer Pharma Japan (Inst), Gilead Sciences (Inst)
Se-Hoon Lee
Honoraria: AstraZeneca/MedImmune, Roche, Lilly, Amgen, Yuhan, Merck Sharp & Dohme
Consulting or Advisory Role: AstraZeneca, Roche, Pfizer, Lilly, BMS/Ono, Takeda, Janssen, IMBdx, Abion, BeiGene, Daiichi Sankyo, ImmuneOncia, Merck (German), Merck Sharp & Dohme, Novartis
Speakers' Bureau: Abion
Research Funding: AstraZeneca (Inst), Lunit (Inst), Merck Sharp & Dohme (Inst)
David Planchard
Honoraria: Prime Oncology, PeerVoice
Consulting or Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Novartis, Roche, Pfizer, MSD Oncology, Celgene, BeiGene, Samsung, AbbVie, Janssen, Daiichi Sankyo/AstraZeneca, Pierre Fabre, Seagen, Gilead Sciences, Anheart Therapeutics
Research Funding: AstraZeneca/MedImmune (Inst), Bristol Myers Squibb (Inst), Boehringer Ingelheim (Inst), Lilly (Inst), Merck (Inst), Novartis (Inst), Pfizer (Inst), Roche (Inst), Sanofi/Aventis (Inst), Taiho Pharmaceutical (Inst), Daiichi Sankyo (Inst), AbbVie (Inst), Janssen (Inst), Pierre Fabre (Inst), Seagen (Inst)
Christina Baik
Consulting or Advisory Role: AstraZeneca, Pfizer, Janssen, Boehringer Ingelheim, Daiichi Sankyo/UCB Japan, Genentech/Roche
Research Funding: Loxo (Inst), AstraZeneca (Inst), Pfizer (Inst), Spectrum Pharmaceuticals (Inst), Blueprint Medicines (Inst), Daiichi Sankyo (Inst), Rain Therapeutics (Inst), AbbVie (Inst), TP Therapeutics (Inst), Lilly (Inst), Janssen (Inst), Nuvalent, Inc (Inst), Boehringer Ingelheim (Inst)
Martha Li
Employment: AbbVie
Stock and Other Ownership Interests: AbbVie
Peter Ansell
Employment: AbbVie
Stock and Other Ownership Interests: AbbVie
Summer Xia
Employment: AbbVie, Lilly
Stock and Other Ownership Interests: AbbVie, Lilly
Travel, Accommodations, Expenses: AbbVie
Ellen Bolotin
Employment: AbbVie
Jim Looman
Stock and Other Ownership Interests: AbbVie
Honoraria: AbbVie
Christine Ratajczak
Employment: AbbVie
Stock and Other Ownership Interests: AbbVie
No other potential conflicts of interest were reported.
PRIOR PRESENTATION
Presented in part at the ASCO Annual Meeting, Chicago, IL, May 31-June 3, 2024; the ASCO Annual Meeting, Chicago, IL, June 3-7, 2022; and the American Association for Cancer Research Annual Meeting, virtual, April 10-15 and May 17-21, 2021.
CLINICAL TRIAL INFORMATION
NCT03539536 (LUMINOSITY)
DATA SHARING STATEMENT
A data sharing statement provided by the authors is available with this article at https://doi.org/10.1200/JCO.24.00720.
AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual, and trial-level data (analysis data sets), as well as other information (eg, protocols, clinical study reports, or analysis plans) as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. These clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing agreement. Data requests can be submitted at any time after approval in the US and Europe and after acceptance of this manuscript for publication. The data will be accessible for 12 months, with possible extensions considered. For more information on the process, or to submit a request, visit the following link: https://www.abbvieclinicaltrials.com/hcp/data-sharing/.
AUTHOR CONTRIBUTIONS
Conception and design: D. Ross Camidge, Jonathan Goldman, Nicolas Girard, Aaron S. Mansfield, Summer Xia, Ellen Bolotin, Jim Looman, Christine Ratajczak
Administrative support: Nicolas Girard, Shun Lu
Provision of study materials or patients: Jair Bar, Hidehito Horinouchi, Jonathan Goldman, Elena Filippova, Tudor Ciuleanu, Nathalie Daaboul, Chunling Liu, Penelope Bradbury, Mor Moskovitz, Nuran Katgi, Pascale Tomasini, Nicolas Girard, Ji-Youn Han, Shang-Yin Wu, Aaron S. Mansfield, Chih-Hsi Kuo, Kazumi Nishino, Shun Lu
Collection and assembly of data: Jair Bar, Hidehito Horinouchi, Jonathan Goldman, Elena Filippova, Nathalie Daaboul, Chunling Liu, Penelope Bradbury, Mor Moskovitz, Nuran Katgi, Pascale Tomasini, Nicolas Girard, Kristof Cuppens, Ji-Youn Han, Shang-Yin Wu, Aaron S. Mansfield, Chih-Hsi Kuo, Kazumi Nishino, Christina Baik, Martha Li, Peter Ansell, Ellen Bolotin, Shun Lu
Data analysis and interpretation: D. Ross Camidge, Jonathan Goldman, Fedor Moiseenko, Irfan Cicin, Tudor Ciuleanu, Pascale Tomasini, Alona Zer, Kristof Cuppens, Ji-Youn Han, Shobhit Baijal, Aaron S. Mansfield, Se-Hoon Lee, David Planchard, Christina Baik, Martha Li, Peter Ansell, Summer Xia, Ellen Bolotin, Christine Ratajczak
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors
AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Telisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met Protein–Overexpressing Advanced Nonsquamous EGFR-Wildtype Non–Small Cell Lung Cancer in the Phase II LUMINOSITY Trial
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.
Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).
D. Ross Camidge
Honoraria: Roche, Takeda, AstraZeneca, Daiichi Sankyo, Bio-Thera, Ribon Therapeutics, AbbVie, Apollomics, Elevation Oncology, EMD Serono, Helsinn Therapeutics, Lilly, Nuvalent, Inc, Seagen, Kestrel Labs, Amgen Astellas BioPharma, Janssen, OnKure, Mersana, Sanofi, Anheart Therapeutics, BeiGene, Hengrui Pharmaceutical, Puma Biotechnology, Turning Point Therapeutics, BeiGene, Dizal Pharma, Hummingbird, Mirati Therapeutics, Nalo Therapeutics
Research Funding: Inivata (Inst)
Jair Bar
Stock and Other Ownership Interests: Causalis
Consulting or Advisory Role: Pfizer, Bristol Myers Squibb, AstraZeneca, AbbVie, MSD, Takeda, Bayer, Novartis, Roche, Merck Serono, BeiGene
Research Funding: AstraZeneca/MedImmune (Inst), MSD (Inst), Pfizer (Inst), Roche (Inst), AbbVie (Inst), Novartis (Inst), Takeda (Inst), Oncohost (Inst), Immunai (Inst)
Hidehito Horinouchi
Honoraria: Lilly, Bristol Myers Squibb Japan, Kyowa Hakko Kirin, Chugai Pharma, AstraZeneca, MSD Oncology, AbbVie, Amgen, Taiho Pharmaceutical, Ono Pharmaceutical, Merck Serono, Pfizer, Daiichi Sankyo
Consulting or Advisory Role: AstraZeneca, Chugai Pharma, AbbVie, Daiichi Sankyo, Yuhan, Novocure, Seagen
Research Funding: Taiho Pharmaceutical (Inst), Merck Serono (Inst), Novartis (Inst), MSD Oncology (Inst), Chugai Pharma (Inst), Ono Pharmaceutical (Inst), A2 Healthcare (Inst), Daiichi Sankyo (Inst), BMKK (Inst), AbbVie (Inst), AstraZeneca (Inst), Amgen (Inst), Boehringer Ingelheim (Inst)
Jonathan Goldman
Consulting or Advisory Role: AstraZeneca, AbbVie, Genentech, Regeneron, Jazz Pharmaceuticals, Gritstone Bio, Gilead Sciences, Daiichi Sankyo/AstraZeneca, Summit Biomedical
Research Funding: Lilly (Inst), Genentech/Roche (Inst), Bristol Myers Squibb (Inst), AstraZeneca/MedImmune (Inst), AbbVie (Inst), Advaxis (Inst), Pfizer (Inst), Summit Biomedical (Inst), EMD Serono (Inst), Amgen (Inst), Lyell Immunopharma (Inst), Genmab (Inst), Astellas Pharma (Inst), GlaxoSmithKline (Inst), Janssen (Inst)
Open Payments Link:https://openpaymentsdata.cms.gov/physician/124819
Fedor Moiseenko
Honoraria: AstraZeneca, Takeda, Sanofi/Aventis, Pfizer/EMD Serono, BioCad, Novartis, MSD Oncology, Merck, Roche, Bristol Myers Squibb, Boehringer Ingelheim, Lilly
Consulting or Advisory Role: Boehringer Ingelheim, AstraZeneca, Pfizer, Sanofi
Speakers' Bureau: Takeda, Roche, Bristol Myers Squibb, Boehringer Ingelheim, Lilly
Research Funding: BioCad (Inst)
Travel, Accommodations, Expenses: Sanofi/Aventis, Bristol Myers Squibb, AstraZeneca, Boehringer Ingelheim, Boehringer Ingelheim
Other Relationship: Pfizer (Inst), AstraZeneca (Inst), Roche, Bristol Myers Squibb (Inst), MSD Oncology
Elena Filippova
Honoraria: Pfizer, Takeda, AbbVie
Speakers' Bureau: Pfizer
Irfan Cicin
Consulting or Advisory Role: Pfizer (Inst), MSD Oncology (Inst), Roche (Inst), Novartis/Ipsen (Inst), Lilly (Inst), Bristol Myers Squibb (Inst), SERVIER (Inst), Abdi Ibrahim (Inst), Nobelpharma (Inst), AbbVie (Inst), Teva, Janssen Oncology (Inst), Takeda (Inst), Gen (Inst), Astellas Pharma (Inst), Gilead Sciences (Inst)
Speakers' Bureau: Novartis (Inst), Roche (Inst), Bristol Myers Squibb (Inst), Pfizer (Inst), Abdi Ibrahim (Inst), Astellas Pharma, MSD (Inst), MSD (Inst), Gen (Inst), Teva (Inst)
Tudor Ciuleanu
Consulting or Advisory Role: Astellas Pharma, Janssen, Bristol Myers Squibb, Merck Serono, Amgen, Roche, Pfizer, Boehringer Ingelheim, Lilly, AstraZeneca, Merck Sharp & Dohme, Sanofi, Novartis, SERVIER, A&D Pharma, Accord Healthcare, MagnaPharm, Takeda
Travel, Accommodations, Expenses: Pfizer, Sanofi, Boehringer Ingelheim, Merck, Servier, Ipsen, Amgen, A&D Pharma, AstraZeneca, Roche/Genentech, Bristol Myers Squibb, MSD, Lilly, Janssen, Novartis, Astellas Pharma
Nathalie Daaboul
Consulting or Advisory Role: AstraZeneca Canada, Bristol Myers Squibb/Celgene, Merck, Pfizer, Roche, Takeda, Amgen, Taiho Oncology, Eisai
Penelope Bradbury
(OPTIONAL) Uncompensated Relationships: AbbVie
(OPTIONAL) Uncompensated Relationships: Bristol Myers Squibb
(OPTIONAL) Uncompensated Relationships: Mirati Therapeutics
(OPTIONAL) Uncompensated Relationships: Merck
(OPTIONAL) Uncompensated Relationships: Raptor Pharmaceuticals
Mor Moskovitz
Honoraria: MSD, BMSi, Roche, Takeda, AbbVie, AstraZeneca, Johnson & Johnson/Janssen
Consulting or Advisory Role: AstraZeneca, MSD Oncology, Takeda, Roche, Pfizer, JNJ, Novartis, Amgen
Travel, Accommodations, Expenses: Pfizer, MSD, Roche
Pascale Tomasini
Consulting or Advisory Role: AstraZeneca, Roche, Bristol Myers Squibb Foundation, Takeda, Amgen, Janssen
Travel, Accommodations, Expenses: Bristol Myers Squibb/Pfizer, AstraZeneca, Takeda
Alona Zer
Stock and Other Ownership Interests: Nixio
Honoraria: MSD, Roche, Bristol Myers Squibb, AstraZeneca, Takeda, Novartis
Consulting or Advisory Role: Lilly, Boehringer Ingelheim, Roche, MSD, Oncotest/Rhenium, Oncohost
Research Funding: Bristol Myers Squibb (Inst)
Travel, Accommodations, Expenses: AstraZeneca, MSD, Roche
Other Relationship: Beyond Air
Nicolas Girard
Employment: AstraZeneca
Consulting or Advisory Role: Roche, Lilly, AstraZeneca, Novartis, Pfizer, Bristol Myers Squibb, MSD, Takeda, Janssen, Sanofi, AMGEN, Gilead Sciences, BeiGene, AbbVie, Daiichi Sankyo/AstraZeneca, LEO Pharma, Ipsen
Research Funding: Roche (Inst), AstraZeneca (Inst), BMS (Inst), MSDAvenir (Inst)
Travel, Accommodations, Expenses: Roche, Janssen Oncology
Kristof Cuppens
Consulting or Advisory Role: Bristol Myers Squibb, MSD, AstraZeneca/MedImmune, Roche/Genentech, Janssen, Amgen
Research Funding: Bristol Myers Squibb (Inst), AstraZeneca/MedImmune
Expert Testimony: AstraZeneca, MSD
Travel, Accommodations, Expenses: Roche/Genentech, AstraZeneca, Janssen, MSD
Ji-Youn Han
Honoraria: AstraZeneca, Takeda, Novartis, Merck, Janssen, Pfizer, Yuhan
Consulting or Advisory Role: Novartis, Merck, Takeda, Janssen, Lantern Pharma, Amgen, AstraZeneca, Daiichi Sankyo/UCB Japan, Oncovix, AbbVie
Research Funding: Roche, Pfizer
Shobhit Baijal
Honoraria: AbbVie, Agilent, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb Foundation, Chugai Pharma, FoundationOne, Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Merck Serono, Merck Sharp & Dohme, Novartis, Pierre Fabre, Pfizer, Roche, SERVIER, Sanofi and Takeda, Daiichi Sankyo
Aaron S. Mansfield
Honoraria: Roche
Consulting or Advisory Role: Genentech (Inst), Bristol Myers Squibb (Inst), AbbVie (Inst), AstraZeneca (Inst), Janssen (Inst), BeiGene (Inst), Takeda (Inst), Genzyme (Inst), Gilead Sciences (Inst), Johnson & Johnson Global Services (Inst)
Speakers' Bureau: Chugai/Roche (Inst)
Research Funding: Novartis (Inst), Verily (Inst), Bristol Myers Squibb (Inst)
Travel, Accommodations, Expenses: AbbVie, Roche
Other Relationship: Mesothelioma Applied Research Foundation
Chih-Hsi Kuo
Honoraria: Boehringer Ingelheim, AstraZeneca, Roche, Pfizer, Lilly, Novartis, Ono Pharmaceutical, Chugai Pharma, Merck, Janssen Oncology, Takeda, Guardant Health AMEA
Consulting or Advisory Role: AstraZeneca, Boehringer Ingelheim, Lilly, Merck, Chugai Pharma, Takeda, Novartis, Guardant Health AMEA
Kazumi Nishino
Honoraria: Chugai Pharma, AstraZeneca Japan, Nippon Boehringer Ingelheim, Lilly Japan, Novartis, Merck, Pfizer, Janssen, Bristol Myers Squibb Japan, Nippon Kayaku
Consulting or Advisory Role: Pfizer, AstraZeneca, Lilly Japan
Research Funding: Ono Pharmaceutical (Inst), Taiho Pharmaceutical (Inst), MSD (Inst), Daiichi Sankyo/UCB Japan (Inst), AbbVie (Inst), Amgen (Inst), Eisai (Inst), Sanofi (Inst), Janssen (Inst), Novartis (Inst), Pfizer (Inst), Lilly Japan (Inst), Merck (Inst), Takeda (Inst), Chugai Pharma (Inst), Merus (Inst), Bayer Pharma Japan (Inst), Gilead Sciences (Inst)
Se-Hoon Lee
Honoraria: AstraZeneca/MedImmune, Roche, Lilly, Amgen, Yuhan, Merck Sharp & Dohme
Consulting or Advisory Role: AstraZeneca, Roche, Pfizer, Lilly, BMS/Ono, Takeda, Janssen, IMBdx, Abion, BeiGene, Daiichi Sankyo, ImmuneOncia, Merck (German), Merck Sharp & Dohme, Novartis
Speakers' Bureau: Abion
Research Funding: AstraZeneca (Inst), Lunit (Inst), Merck Sharp & Dohme (Inst)
David Planchard
Honoraria: Prime Oncology, PeerVoice
Consulting or Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Novartis, Roche, Pfizer, MSD Oncology, Celgene, BeiGene, Samsung, AbbVie, Janssen, Daiichi Sankyo/AstraZeneca, Pierre Fabre, Seagen, Gilead Sciences, Anheart Therapeutics
Research Funding: AstraZeneca/MedImmune (Inst), Bristol Myers Squibb (Inst), Boehringer Ingelheim (Inst), Lilly (Inst), Merck (Inst), Novartis (Inst), Pfizer (Inst), Roche (Inst), Sanofi/Aventis (Inst), Taiho Pharmaceutical (Inst), Daiichi Sankyo (Inst), AbbVie (Inst), Janssen (Inst), Pierre Fabre (Inst), Seagen (Inst)
Christina Baik
Consulting or Advisory Role: AstraZeneca, Pfizer, Janssen, Boehringer Ingelheim, Daiichi Sankyo/UCB Japan, Genentech/Roche
Research Funding: Loxo (Inst), AstraZeneca (Inst), Pfizer (Inst), Spectrum Pharmaceuticals (Inst), Blueprint Medicines (Inst), Daiichi Sankyo (Inst), Rain Therapeutics (Inst), AbbVie (Inst), TP Therapeutics (Inst), Lilly (Inst), Janssen (Inst), Nuvalent, Inc (Inst), Boehringer Ingelheim (Inst)
Martha Li
Employment: AbbVie
Stock and Other Ownership Interests: AbbVie
Peter Ansell
Employment: AbbVie
Stock and Other Ownership Interests: AbbVie
Summer Xia
Employment: AbbVie, Lilly
Stock and Other Ownership Interests: AbbVie, Lilly
Travel, Accommodations, Expenses: AbbVie
Ellen Bolotin
Employment: AbbVie
Jim Looman
Stock and Other Ownership Interests: AbbVie
Honoraria: AbbVie
Christine Ratajczak
Employment: AbbVie
Stock and Other Ownership Interests: AbbVie
No other potential conflicts of interest were reported.
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