Background: Teliso-V is an anti-c-Met antibody conjugated with a tubulin inhibitor MMAE. The aim of this phase 2 trial (NCT03539536) is to explore safety and efficacy of teliso-V in cohorts (based on histopathology and EGFR mutation) and subgroups (based on c-Met expression) of patients with c-Met+ advanced NSCLC (stage 1), followed by expansion into an appropriately selected population for further evaluation of safety and efficacy (stage 2).Methods: Patients had ECOG ≤ 1 with 1-2 prior lines of therapy including cytotoxic chemotherapy, immunotherapy and targeted therapy. c-Met status was determined centrally by IHC (SP44 antibody). Membrane staining ≥ 25% 3+ or ≥ 75% 1+ was considered positive for non-squamous and squamous, respectively. Teliso-V dose was 1.9 mg/kg Q2W. Primary endpoint was objective response rate (ORR) per central review in patients with ≥ 12 weeks follow-up. Secondary endpoints were duration of response, disease control rate, PFS and OS.Results: ORR was 35.1% in the non-squamous EGFR WT cohort (53.8% in c-Met high group and 25.0% in c-Met intermediate group; Table), but was modest in the squamous and EGFR Mu cohorts. G3 or higher AEs occurred in 50/113 (44%) patients, with most common (≥ 2%) being malignant neoplasm progression (6.2%), pneumonia (5.3%), hyponatremia (4.4%), anemia (2.7%), dyspnea (2.7%), fatigue (2.7%), increased GGT (2.7%), peripheral sensory neuropathy (2.7%), and pneumonitis (2.7%). G5 AEs investigators considered possibly related to teliso-V were sudden death, dyspnea, and pneumonitis (1 event each). Conclusions: ORR in non-squamous EGFR WT NSCLC was encouraging with a tolerable safety profile, and this cohort met prespecified criteria to transition to stage 2. In this cohort, ORR was highest in the c-Met high group, though also clinically meaningful in the intermediate group. Enrollment into the squamous cohort was stopped. Enrollment into the EGFR MU cohort will continue until the next interim analysis.

NSCLC GroupN(Total=88)Confirmed ResponsesORR(95% CI)
NSQ EGFR WT 37 13 35.1% (20,53) 
c-Met high (≥ 50% positive, 3+ staining) 13 53.8% (25, 81) 
c-Met int(25-49%, 3+ staining) 24 25.0% (10,47) 
NSQ EGFR MU 30 13.3% (4,31) 
c-Met high (≥ 50%, 3+ staining) 22 18.2% (5, 40) 
c-Met int (25-49%, 3+ staining) 0 (-,-) 
SQUAMOUS(≥ 75%, 1+ staining) 21 14.3% (3, 36) 
NSCLC GroupN(Total=88)Confirmed ResponsesORR(95% CI)
NSQ EGFR WT 37 13 35.1% (20,53) 
c-Met high (≥ 50% positive, 3+ staining) 13 53.8% (25, 81) 
c-Met int(25-49%, 3+ staining) 24 25.0% (10,47) 
NSQ EGFR MU 30 13.3% (4,31) 
c-Met high (≥ 50%, 3+ staining) 22 18.2% (5, 40) 
c-Met int (25-49%, 3+ staining) 0 (-,-) 
SQUAMOUS(≥ 75%, 1+ staining) 21 14.3% (3, 36) 

Citation Format: D. Ross Camidge, Fedor Moiseenko, Irfan Cicin, Hidehito Horinouchi, Elena Filippova, Jair Bar, Shun Lu, Pascale Tomasini, Christopher Ocampo, Danielle Sullivan, David Maag, Jonathan W. Goldman. Telisotuzumab vedotin (teliso-v) monotherapy in patients with previously treated c-Met+ advanced non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT179.