Abstract CT214: Preliminary efficacy of telisotuzumab vedotin (Teliso-V) treatment in the 2L/3L setting in MET gene amplified (MET Amp), c-Met protein overexpressing (c-Met OE), non-squamous, non-small cell lung cancer (NSQ NSCLC): Retrospective analysis of LUMINOSITY

Abstract Background: Teliso-V is a first-in-class c-Met-directed antibody-drug conjugate comprising the monoclonal antibody telisotuzumab, a cleavable valine-citrulline linker, and the potent microtubule polymerization inhibitor monomethyl auristatin E. In a Phase 2 study (LUMINOSITY, NCT03539536), Teliso-V has shown an acceptable safety profile and encouraging efficacy in c-Met OE NSQ NSCLC. In NSCLC, while c-Met OE is more common than MET Amp, occurring in 25% of patients (pts) versus 1-5%, respectively, ~90% of MET Amp tumors are c-Met OE. We performed a retrospective analysis of LUMINOSITY to characterize the efficacy of Teliso-V in previously treated pts with MET Amp, c-Met OE NSQ NSCLC. Methods: Pts had locally advanced/metastatic NSQ NSCLC, ≤2 prior lines of systemic therapy, ≤1 line of chemotherapy, MET Amp by fluorescence in situ hybridization (FISH), and tumors that were c-Met OE by central immunohistochemistry (IHC). MET Amp was defined as a ratio of ≥1.8 MET gene copy number (GCN) to chromosome 7 (CEP7) CN by FISH with levels of amplification defined as high, ≥5; intermediate (int), >2.2 - <5; or low, ≥1.8 - ≤2.2. MET GCN by FISH was classified as high, ≥10; int, 5 - <10; or low, <5. c-Met OE was defined as ≥25% of tumor cells at 3+ intensity by IHC; patients were classified as MET IHC 3/25 (25 - 49% tumor cells at 3+) or MET IHC 3/50 (≥50% tumor cells at 3+). Teliso-V was dosed at 1.9 mg/kg IV Q2W. Results: As of 27 May 2021, 10 pts with MET Amp were treated with Teliso-V. The median age was 69 (48-75), 9 pts were male, 5 were White, 9 had a history of smoking (current or former), and 9 had an ECOG score of 0-1. The median MET/CEP7 ratio was 3.3 (1.84-12.17) with 4, 1, and 5 pts having high, int, and low levels of amplification, respectively. The median MET GCN was 10.98 (6.95-65.00) with 6, 3, and 1 pts having high, int, and low GCN, respectively. 7 pts were MET IHC 3/50 and 3 were MET IHC 3/25. Pts with MET Amp treated with Teliso-V monotherapy had an ORR of 80% (95% CI [44.4, 97.5]; n=8; all partial response) by independent central review, and a disease control rate of 90%. The median duration of response was 6.9 months. Among the 8 responders, 62.5% (n=5/8) are still event-free and being followed up for disease assessment. Teliso-V monotherapy resulted in median progression-free survival (PFS) of 8.0 months (95% CI [1.3, -]; n=10), compared with 5.7 months (95% CI [2.6, 9.8]) on the last prior line of systemic cancer therapy (n=10). Conclusions: Teliso-V demonstrated a promising ORR in previously treated pts with MET Amp NSQ NSCLC with c-Met OE and improved PFS when compared to last prior systemic cancer therapy. These preliminary data support the ongoing Phase 2 trial of Teliso-V monotherapy in pts with previously untreated MET Amp NSCLC (TeliMET NSCLC-02; NCT05513703), which is currently enrolling. Citation Format: D. Ross Camidge, Jonathan Goldman, Athan Vasilopoulos, Peter Ansell, Summer Xia, Ellen Bolotin, Jim Looman, Christine Ratajczak, Elysa Noon, Shun Lu. Preliminary efficacy of telisotuzumab vedotin (Teliso-V) treatment in the 2L/3L setting in MET gene amplified (MET Amp), c-Met protein overexpressing (c-Met OE), non-squamous, non-small cell lung cancer (NSQ NSCLC): Retrospective analysis of LUMINOSITY [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT214.