A phase 2 randomized study of telisotuzumab adizutecan (ABBV-400, Temab-A) in combination with standard of care (SOC) in patients with metastatic colorectal cancer.

Abstract

TPS255 Background: c-Met protein is often expressed in several solid tumors, including metastatic colorectal cancer (mCRC). Temab-A is an antibody-drug conjugate that targets c-Met protein and is conjugated to a topoisomerase 1 inhibitor payload. A phase 1 study in patients (pts) with advanced solid tumors, including mCRC, reported a manageable safety profile and promising antitumor activity with Temab-A monotherapy (NCT05029882). Herein, we describe a phase 2 study of Temab-A in combination with SOC regimens in pts with mCRC. Methods: This open-label, randomized, global, multicenter, phase 2 study (NCT06820463; AndroMETa-CRC-533) includes 2 substudies. Eligible pts (≥18 years) must have histologically confirmed mismatch repair-proficient mCRC, measurable disease (per RECIST v1.1), and no prior systemic therapy for mCRC. In substudy 1, eligible pts must have KRAS/NRAS -mutant primary tumor or right-sided KRAS/NRAS -wildtype primary tumor. For substudy 2, eligible pts must have KRAS/NRAS/BRAF -wildtype and left-sided primary tumor. Substudies 1 and 2 comprise a dose-escalation (D-ESC; guided by a BOIN design) followed by a dose-expansion (D-EXP) phase. During D-ESC, pts receive escalating doses of Temab-A (Q4W) with either FOLFOX + bevacizumab (BEV; substudy 1: N~18) or 5-fluorouracil (5-FU)–folinic acid + panitumumab (PAN; substudy 2: N~12) in 28-day cycles. During D-EXP, ~135 pts for each substudy are randomized 1:1:1 to high- or low-dose arms (substudy 1: Temab-A + FOLFOX + BEV; substudy 2: Temab-A + 5-FU–folinic acid + PAN) or SOC (substudy 1: FOLFOX + BEV; substudy 2: FOLFOX + PAN). In both substudies, pts receive treatment until disease progression, intolerable toxicity, or other discontinuation criteria are met. Objectives and endpoints are listed in the table. Clinical trial information: NCT06820463 . Objectives Primary Evaluate safety, tolerability, and efficacy (as measured by OR) of Temab-A in combination with SOC regimensOptimize Temab-A dose in combination with SOC regimens Secondary Assess additional efficacy outcomesEvaluate PK of Temab-A in combination with SOC regimens Endpoints Primary OR (CR, PR by Inv) Secondary PFS, DOR, disease control (by Inv), OS Exploratory PROs (in the randomized stages) CR, complete response; DOR, duration of response; Inv, investigator; OR, overall response; OS, overall survival; PFS, progression-free survival; PK, pharmacokinetics; PR, partial response; PROs, patient reported outcomes.