515MO - Phase Ib study of telisotuzumab vedotin (Teliso-V) and osimertinib in patients (Pts) with advanced EGFR-mutated (Mut), c-Met overexpressing (OE) non-small cell lung cancer (NSCLC): Final efficacy and safety updates

Background

Clinical evidence supports c-Met as a target in pts with advanced EGFR-mut NSCLC after progression on osimertinib (O; third-generation EGFR-TKI). Here we report the final results of the Teliso-V (T; first-in-class c-Met–targeting ADC) + O combination arm of the phase 1b study (NCT02099058) in pts with advanced/metastatic EGFR-mut, c-Met OE NSCLC with progression on prior O.

Methods

Pts (≥18 yr) with advanced/metastatic EGFR-mut, c-Met OE (centrally assessed by IHC [Clinical Trial Assay]: 3+ in ≥25% tumor cells) NSCLC with progression on O received T (IV Q2W 1.6 or 1.9 mg/kg) + O (oral 80 mg QD). Pts in expansion phases had ≤2 prior lines (L) of therapy, including O.

Results

As of March 23, 2023, 41 pts were enrolled. Data for 38 pts with sufficient follow-up are shown (T [1.6 mg/kg, n=20; 1.9 mg/kg, n=18] + O); median age was 60 yr; 40/42/18% of pts received 1/2/>2 prior L for metastatic NSCLC, including platinum-based therapy in 47%. Median number of T cycles (28 d/cycle) was 6 (range, 1–30). No DLTs were observed in safety evaluation cohorts. AEs possibly related to T occurred in 37 (97%; any grade [G]) pts; most common (≥20%) were peripheral sensory neuropathy (50%), peripheral edema (21%), and nausea (21%). Of these, G ≥3 were reported in 12 (32%) pts; most common (≥5%) were anemia (11%), and peripheral motor and sensory neuropathy (5% each). AEs leading to T discontinuation/interruption/reduction occurred in 24/58/37% of pts. No deaths related to T or O were reported. Overall T + O efficacy is shown in the table. Table: 515MO

*RECIST v1.1. All PR; ^†95% CI; ^‡FISH data missing for 11 pts; No. events/No. pts censored: ^§9/11; ^¶3/16; ^#24/14; **17/21.

Conclusions

T + O showed tolerable safety and encouraging efficacy in pts with EGFR-mut, c-Met OE NSCLC with progression on O, regardless of MET amplification status or number of prior L, with an ORR of 53/50% and DCR of 71/76% as per investigators/ICR. T + O may be a potential option for these pts and warrants further clinical investigation.

Clinical trial identification

NCT02099058.

Editorial acknowledgement

Medical writing support was provided by Iratxe Abarrategui, PhD, CMPP, of Aptitude Health, the Netherlands, and funded by AbbVie.

Legal entity responsible for the study

AbbVie Inc.

Funding

AbbVie.

Disclosure

H. Horinouchi: Financial Interests, Institutional, Research Funding: AbbVie, MSD, Chugai/Roche, Daiichi Sankyo, Janssen, Genomic Health; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, MSD, Lilly, BMS, Ono, Janssen, Kyowa Kirin, Nihonkayaku. B.C. Cho: Financial Interests, Personal, Royalties: Champions Oncology, Crown Bioscience, Imagen; Financial Interests, Institutional, Research Funding: MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp., GI Innovation, GI Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Oncology, CJ Bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Ja; Financial Interests, Personal, Advisory Role: Abion, BeiGene, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus Therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI Cell, Guardant, HK Inno.N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Janssen, MedPa; Financial Interests, Personal, Full or part-time Employment: Yonsei University Health System; Financial Interests, Personal, Advisory Board: KANAPH Therapeutics Inc, BridgeBio Therapeutics, Cyrus Therapeutics, Guardant Health, Oscotec Inc; Financial Interests, Personal, Speaker’s Bureau: ASCO, AstraZeneca, Guardant, Roche, ESMO, IASLC, Korean Cancer Association, Korean Society of Medical Oncology, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, Pfizer; Financial Interests, Personal, Stocks/Shares: TherCanVac Inc, Gencurix Inc, Bridgebio Therapeutics, KANAPH Therapeutic Inc, Cyrus Therapeutics, Interpark Bio Convergence Corp., J INTS Bio; founder of DAAN Biotherapeutics; Financial Interests, Personal, Member of Board of Directors: Interpark Bio Convergence Corp., J INTS Bio. D.R. Camidge: Financial Interests, Personal, Advisory Role: AbbVie, Apollomics, AstraZeneca, Daiichi Sankyo, Elevation, Kestrel, Nuvalent, Seattle Genetics, Takeda, Turning Point, Amgen, Anchiano, Bio-Thera, BMS, Eisai, EMD Serono, Eli Lilly, GSK, Helsinn, Janssen, OnKure, Mersana, Pfizer, Qilu, Roche, Sanofi, CBT; Financial Interests, Personal, Research Funding: Inivata; Financial Interests, Institutional, Research Funding: AbbVie, AstraZeneca, Dizal, Inhibrx, Karyopharm, Pfizer, Phosplatin, PsiOxus, Rain, Roche/Genentech, Seattle Genetics, Takeda, Turning Point. P. Tomasini: Financial Interests, Institutional, Research Funding: Roche, Janssen; Financial Interests, Personal, Expert Testimony: AstraZeneca, Roche, BMS, AbbVie, Johnson & Johnson, Takeda. Y. Li, A. Vasilopoulos, P. Brunsdon, D. Hoffman, W. Shi, V. Blot: Financial Interests, Personal, Full or part-time Employment: AbbVie ; Financial Interests, Personal, Stocks/Shares: AbbVie. J.W. Goldman: Financial Interests, Institutional, Research Funding: AbbVie, AstraZeneca; Financial Interests, Personal, Speaker, Consultant, Advisor: AbbVie, AstraZeneca. All other authors have declared no conflicts of interest.