387P - Telisotuzumab vedotin (Teliso-V) in combination with osimertinib in patients with advanced EGFR-mutated, c-met overexpressing, non-small cell lung cancer (NSCLC): Safety and efficacy results from phase Ib study

Background

Supporting evidence from previous clinical studies provides a substantiative rationale for Osimertinib (O; third-generation EGFR-TKI) and Teliso-V (T; c-Met TKI inhibitor) combination therapy for the treatment (Tx) of patients (pts) with metastatic/advanced EGFR-mut c-Met overexpressed (OE) NSCLC following progression on prior O. Here we report updated safety and efficacy results of a phase 1b study (NCT02099058) for T+O combination (Arm E).

Methods

Pts (≥18 years) with advanced/metastatic EGFR-mut, c-Met OE (centrally assessed 3+ staining by IHC in ≥ 25% tumor cells) NSCLC who had progressed while on prior O, received T (IV Q2W) + O (oral 80 mg QD). T was dosed at 1.6 mg/kg and 1.9 mg/kg in evaluation phases, and at 1.9 mg/kg in the expansion phase in pts with ≤2 prior lines of systemic therapy, one of which was O.

Results

As of April 7, 2022, 25 pts (median age, 60.0 yrs) were assessed for safety (T [1.6 mg/kg, n=7; 1.9 mg/kg, n=18] + O) and 24 were evaluable for efficacy; 8 (32%) received 1 prior line in metastatic setting; 8 (35%) with < 1 mo from end of first prior O to first study dose; 15 (60%) received prior platinum-based therapy. Median number of T+O cycles (28 days/cycle) was 6 (range: 1 – 23). No DLTs were reported in the evaluation phases. Possibly T-related AEs: any grade (Gr; ≥20%): peripheral sensory neuropathy (40%), nausea and peripheral oedema (24% each), anaemia and paraesthesia (20% each); Gr ≥3 (>5%): anemia (12%) and peripheral motor neuropathy (8%). No T- or O-related Gr 5 AEs were reported. Overall T+O efficacy (ORR, DCR, DoR) is shown in the table. Table: 387P

*RECIST v1.1; ^†total 23 pts, c-Met IHC score <25% 3+, n=1; ^‡data missing for 2 pts; ^§data still maturing; NR, not reached

Conclusions

T + O combination demonstrated tolerable safety and encouraging efficacy with an overall ORR of 50% and DCR of 75% in pts with EGFR-mut, c-Met OE NSCLC who progressed on prior O. This combination may be a potential 2L and 3L Tx option likely to benefit this specific population and deserves further clinical exploration.

Clinical trial identification

NCT02099058.

Editorial acknowledgement

AbbVie and the authors thank all the trial investigators and the patients who participated in this clinical trial. Medical writing support was provided by Gina E. Elsen, PhD, of AbbVie and funded by AbbVie.

Legal entity responsible for the study

AbbVie.

Funding

AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the abstract. All authors had access to relevant data and participated in the drafting, review, and approval of this abstract. No honoraria or payments were made for authorship.

Disclosure

H. Horinouchi: Financial Interests, Institutional, Research Grant: AbbVie, Merck, Chugai/Roche, Daiichi Sankyo, Janssen, Genomic Health; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Merck Sharp & Dohme, Lilly, Bristol Myers Squibb, Ono, Janssen, Kyowa Kirin, Nihonkayaku. J.W. Goldman: Financial Interests, Institutional, Research Grant: AbbVie, AstraZeneca; Financial Interests, Personal, Other, Honoraria: AbbVie, AstraZeneca. P. Tomasini: Financial Interests, Institutional, Research Grant: Roche, Janssen; Financial Interests, Personal, Expert Testimony: AstraZeneca, Roche, Bristol Myers Squibb, AbbVie, Johnson & Johnson, Takeda. M. Dunbar, D. Hoffman, A. Parikh, V. Blot: Financial Interests, Personal, Full or part-time Employment: AbbVie; Financial Interests, Personal, Stocks/Shares: AbbVie. D.R. Camidge: Financial Interests, Institutional, Research Grant: Inivata; Financial Interests, Institutional, Other, Company-sponsored trials at institution: AbbVie, AstraZeneca, Dizal, Inhibrx, Karyopharm, Pfizer, Phosplatin, PsiOxus, Rain, Roche/Genentech, Seattle Genetics, Takeda, Turning Point; Financial Interests, Personal, Advisory Role: AbbVie, Apollomics, AstraZeneca, Daiichi Sankyo, Elevation, Kestrel, Nuvalent, Seattle Genetics, Takeda, Turning Point, Amgen, Anchiano, Bio-Thera, Bristol Myers Squibb, Eisai, EMD Serono, Eli Lilly, GlaxoSmithKline, Helsinn, Janssen, OnKure, Mersana, Pfizer, Qilu, Roche, Sanofi, CBT Pharmaceuticals, G1 Therapeutics, Blueprint, Achilles, BeyondSpring, Archer, Medtronic, Ribon. All other authors have declared no conflicts of interest.