Telisotuzumab adizutecan (ABBV-400; Temab-A), a c-Met protein–targeting antibody-drug conjugate (ADC), in patients (pts) with advanced <i>EGFR</i> -mutated (MT) non-squamous (NSQ) non-small cell lung cancer (NSCLC): Results from a phase 1 study.

Abstract

8512 Background: c-Met protein (also known as MET protein) expression is increased in NSCLC and is a negative prognostic indicator. Temab-A is an ADC comprising the c-Met protein–targeting mAb telisotuzumab conjugated to a novel topoisomerase 1 inhibitor payload. A phase 1 study (NCT05029882) of Temab-A in advanced solid tumors is ongoing. In dose expansion, Temab-A had manageable safety and promising efficacy in pts with NSQ EGFR wildtype NSCLC ( Ann Oncol . 2024;35:1257MO). Herein, we present the results for pts with advanced EGFR MT NSQ NSCLC. Methods: Pts (≥18 yr) whose disease had progressed after platinum-based chemotherapy doublet and tyrosine kinase inhibitor(s) (TKIs) were enrolled. Pts received Temab-A at 2.4 (n=36) or 3.0 (n=5) mg/kg Q3W. Primary objectives were evaluating safety, tolerability, PK, and preliminary efficacy of Temab-A. Tumor tissue c-Met protein expression was assessed centrally by IHC. Results: Forty-one pts were enrolled in the EGFR MT cohort. Median age was 64 yr (43–88), 63% were female, and 32% had baseline brain metastases. Median prior therapies was 3 (1–8); 93% had prior anti-EGFR treatment. Median treatment duration was 9.2 months; median follow-up was 9.7 months. TEAEs of any grade/grade ≥3 occurred in 100%/73% of pts. The most common any-grade TEAEs were hematologic (83%) and gastrointestinal (81%); any-grade TEAEs in ≥30% of pts were anemia (63%), nausea (61%), vomiting (37%), decreased appetite (34%), and neutropenia (34%). Grade ≥3 TEAEs were mostly hematologic (42%), and most common were anemia (27%) and neutropenia (22%). The any-grade adjudicated interstitial lung disease/pneumonitis rate was 7% (grade ≥3: 2%). TEAEs leading to discontinuation occurred in 20% of pts. Four deaths occurred; 1 (pneumonitis) was considered related to study drug. All pts with post-baseline data had some decrease in tumor burden. ORR was 63% (Table); similarly high ORR was observed regardless of c-Met protein expression. Responses occurred irrespective of EGFR L858R alterations, exon 19 deletions, or TKI resistance mutations including T790M and C797S. As of the data cut (Sep 2024), 19 (46%) pts remain on treatment. Time-to-event endpoints are immature; to date, 54% of responders have a DOR of ≥6 months. Exploratory biomarker analysis is ongoing. Conclusions: Temab-A has a manageable safety profile with promising clinical activity in pts with 3L+ NSQ EGFR MT NSCLC, meriting further investigation. Clinical trial information: NCT05029882 . Efficacy NSQ EGFR MT NSCLC(n=41) Best overall response, a n (%) PR SD NE/Not assessed 26 (63)12 (29)3 (7) ORR, a n (%) 26 (63) CBR12, a n (%) 34 (83) P[PFS at 6 mo], % (95% CI) 80 (63, 89) P[OS at 6 mo], % (95% CI) 93 (79, 98) a Confirmed responses. P, probability.