Introduction Treatment options for metastatic colorectal cancer (mCRC) in late-line settings remain limited, particularly in patients with microsatellite stable disease. Antibody-drug conjugates (ADCs) targeting tumour-specific pathways represent an emerging strategy to improve outcomes.
Introduction
Treatment options for metastatic colorectal cancer (mCRC) in late-line settings remain limited, particularly in patients with microsatellite stable disease. Antibody-drug conjugates (ADCs) targeting tumour-specific pathways represent an emerging strategy to improve outcomes. Temab-A (ABBV-400), a c-Met–targeting ADC linked to a topoisomerase-1 inhibitor payload, is designed to deliver cytotoxic therapy directly to tumour cells.
Problem Statement
Patients with heavily pretreated mCRC often have a poor prognosis and limited therapeutic options. While targeted therapies and immunotherapy have transformed some subsets, microsatellite-stable, BRAF wild-type mCRC remains a major unmet need. The challenge is to identify treatments that provide meaningful responses with acceptable toxicity.
Summary
This phase I study evaluated Temab-A in advanced solid tumours, with a focus on mCRC. The maximum tolerated dose was established at 3.0 mg/kg, with 2.4 mg/kg every 3 weeks identified as the optimal dose based on safety and activity.
Across 122 patients with mCRC, Temab-A demonstrated promising antitumor activity, with an overall response rate of 15.6% and a disease control rate of nearly 75%. Median progression-free survival was 4.6 months, and overall survival reached 10.4 months, suggesting a clinically meaningful benefit in a refractory population.
Toxicities were common but manageable, predominantly gastrointestinal and hematologic. Treatment discontinuation and mortality rates were relatively low.
Overall, Temab-A shows encouraging early efficacy as a targeted ADC in late-line mCRC, warranting further evaluation in phase II trials and combination strategies.
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