New c-Met Antibody-Drug Conjugate Shows Promise in Late-Stage Colorectal Cancer
Phase I trial of Temab-A reports 15.6% response rate and 74.6% disease control in heavily pretreated metastatic colorectal cancer patients.
Summary
A first-in-human phase I trial tested Temab-A, a novel antibody-drug conjugate that targets the c-Met protein on cancer cells and delivers a topoisomerase 1 inhibitor payload directly to tumors. Among 122 patients with metastatic colorectal cancer who had already failed prior treatments, the drug achieved a 15.6% overall response rate and a 74.6% disease control rate. Median progression-free survival was 4.6 months and overall survival reached 10.4 months. Side effects were mostly gastrointestinal and blood-related, but treatment discontinuations were low at 10%. The 2.4 mg/kg dose every three weeks was identified as the recommended dose moving forward, balancing efficacy with a manageable safety profile.
Detailed Summary
Colorectal cancer remains one of the leading causes of cancer death worldwide, and patients whose disease has progressed through multiple lines of therapy have very limited options. New targeted therapies are urgently needed, particularly for the large subset with microsatellite stable, BRAF wild-type tumors that do not respond to immunotherapy.
This phase I study evaluated Temab-A (telisotuzumab adizutecan, ABBV-400), a novel antibody-drug conjugate (ADC) that pairs a c-Met-targeting antibody with adizutecan, a potent topoisomerase 1 inhibitor payload. By binding to c-Met — a receptor frequently overexpressed in colorectal and other solid tumors — the drug delivers cytotoxic therapy directly to cancer cells while sparing healthy tissue. The trial enrolled patients with advanced solid tumors in dose escalation and then expanded specifically into metastatic colorectal cancer (mCRC).
Across 122 mCRC patients, Temab-A demonstrated an overall response rate of 15.6%, a disease control rate of 74.6%, and a median overall survival of 10.4 months. Responses were more pronounced at the 2.4 mg/kg and 3.0 mg/kg dose levels. The maximum tolerated dose was established at 3.0 mg/kg, while 2.4 mg/kg every three weeks was selected as the recommended phase II dose based on its favorable benefit-risk balance.
Safety data showed that all patients experienced at least one treatment-emergent adverse event, with gastrointestinal (78%) and hematologic (71%) toxicities being most common. Importantly, treatment-related discontinuations occurred in only 10% of patients and treatment-related deaths in 3%, suggesting the toxicity profile is manageable in a heavily pretreated population.
These results position Temab-A as a potentially meaningful option for late-line mCRC, a setting with few effective therapies. Further trials exploring combination strategies and biomarker-selected populations are warranted to maximize clinical benefit.
Key Findings
- Temab-A achieved a 15.6% overall response rate in heavily pretreated metastatic colorectal cancer patients.
- Disease control rate reached 74.6%, with median overall survival of 10.4 months.
- 2.4 mg/kg every 3 weeks selected as recommended phase II dose based on efficacy and tolerability.
- Treatment-related discontinuations were low at 10%, supporting a manageable safety profile.
- Responses were more frequent at higher doses (2.4 and 3.0 mg/kg), guiding dose optimization.
Methodology
This was a first-in-human phase I study (NCT05029882) with a dose escalation phase (57 patients, multiple solid tumor types) followed by a randomized dose optimization expansion in 93 mCRC patients assigned to 1.6, 2.4, or 3.0 mg/kg every three weeks. Primary endpoints included safety, pharmacokinetics, recommended phase II dose, and antitumor efficacy in mCRC. The study is ongoing.
Study Limitations
This summary is based on the abstract only, as the full text is not open access; detailed subgroup analyses, pharmacokinetic data, and biomarker correlations are unavailable. The study is a phase I trial focused on safety and dose-finding, so efficacy conclusions are preliminary and not powered for definitive comparisons. The patient population is heavily pretreated and may not reflect outcomes in earlier lines of therapy.
Enjoyed this summary?
Get the latest longevity research delivered to your inbox every week.