Telisotuzumab adizutecan

Overview

Telisotuzumab adizutecan (Temab‑A; ABBV‑400) is an investigational antibody–drug conjugate (ADC) that targets the c‑Met (MET) receptor and delivers a novel topoisomerase I inhibitor payload (adizutecan). It is being developed for multiple c‑Met–expressing solid tumors and is in an ongoing first‑in‑human Phase 1 program with expansion cohorts, a randomized Phase 2 in metastatic colorectal cancer (mCRC) combinations, and a global Phase 3 monotherapy study in refractory c‑Met–overexpressing mCRC. (ascopubs.org)

Mechanism of action

• Target: c‑Met (hepatocyte growth factor receptor), a receptor tyrosine kinase frequently overexpressed or dysregulated in solid tumors. The telisotuzumab antibody directs the ADC to c‑Met–expressing tumor cells. (ascopubs.org)
• Payload/linker: adizutecan, a potent topoisomerase I inhibitor, attached via a cleavable valine–alanine linker; the conjugation chemistry was optimized to limit systemic payload release in preclinical work. (aacrjournals.org)

Efficacy

Early clinical signals have been reported across tumor types from the ongoing Phase 1 study (NCT05029882):

• Across advanced solid tumors (dose escalation, ASCO 2023): confirmed objective response rate (ORR) 24.4% (11/45); partial responses were seen in colorectal cancer (CRC), non‑small cell lung cancer (NSCLC; EGFR wild‑type and mutant), uterine cancer, and acral melanoma. (ascopubs.org)
• Metastatic colorectal cancer (dose expansion, ASCO 2024):
• ORR by dose: 15% at 2.4 mg/kg (6/40) and 20% at 3.0 mg/kg (8/41); median duration of response 4.1 and 5.5 months, respectively; clinical benefit at 12 weeks 58% and 37%. Responses were enriched (>30% ORR) in patients with higher c‑Met expression, with activity also observed at lower expression levels (≈10–15% ORR). (ascopubs.org)
• ctDNA‑based analyses in mCRC (ASCO GI 2025): confirmed ORR 18% (20/113) in patients with available baseline ctDNA and radiographic data; molecular response in ctDNA associated with higher ORR (≈35% vs 8%) and longer PFS. (ascopubs.org)
• NSCLC: Preliminary activity reported in previously treated EGFR wild‑type non‑squamous NSCLC (ESMO 2024 report) and in an EGFR‑mutant cohort presented at ASCO 2025 with ORR ~63% (company‑reported meeting summary; detailed peer‑reviewed data pending). (dailyreporter.esmo.org)
• Gastroesophageal adenocarcinoma (GEA): Early Phase 1 data presented (ESMO 2024) indicated an ORR of 28.6% in previously treated gastric/GEJ adenocarcinoma; further biomarker analyses presented at ASCO GI 2025. (onclive.com)

Safety

Across Phase 1 CRC cohorts (data cutoff October 2023), the most common treatment‑emergent adverse events (TEAEs) included hematologic toxicities and gastrointestinal symptoms. Any‑grade anemia occurred in 52% (grade ≥3: 30%), neutropenia 37% (grade ≥3: 25%), leukopenia 25% (grade ≥3: 12%), and thrombocytopenia 23% (grade ≥3: 12%); non‑hematologic TEAEs included nausea 57% (grade ≥3: 3%), fatigue 43% (grade ≥3: 2%), vomiting 39% (grade ≥3: 4%). Unadjudicated interstitial lung disease/pneumonitis occurred in 7% (grade ≥3: 2%). Overall tolerability favored 2.4 mg/kg over 3.0 mg/kg with similar activity. (ascopubs.org)

Ongoing and planned trials (selected)

• Phase 1 first‑in‑human study in advanced solid tumors (monotherapy and combinations): NCT05029882. (ascopubs.org)
• Phase 2 randomized study in previously treated mCRC: ABBV‑400 plus fluorouracil/folinic acid/bevacizumab (F+FA+bev) vs standard regimens to determine optimal dose (e.g., M24‑311). (ascopubs.org)
• Phase 3 AndroMETa‑CRC‑064: ABBV‑400 monotherapy vs trifluridine/tipiracil (Lonsurf) plus bevacizumab in c‑Met–overexpressing refractory mCRC; estimated primary completion April 2029 (NCT06614192). (medsearchglobal.com)

Further reading

• ASCO 2023 dose‑escalation abstract (first‑in‑human): First‑in‑human study of ABBV‑400… J Clin Oncol 2023;41(16_suppl):3015. (ascopubs.org)
• ASCO 2024 CRC expansion oral: ABBV‑400 in CRC cohorts (efficacy and safety table). (ascopubs.org)
• ASCO GI 2025 ctDNA/PK‑PD analyses in mCRC. (ascopubs.org)
• AACR 2023 mechanistic abstract on payload/linker: ABBV‑400 delivers a novel topoisomerase‑1 inhibitor to c‑Met–positive tumors. (aacrjournals.org)
• Review compendium listing ABBV‑400 (mechanism, target, and Phase 3 status). (jhoonline.biomedcentral.com)
• Phase 3 study listing (AndroMETa‑CRC‑064). (medsearchglobal.com)

Notes: All efficacy and safety results are investigational, from early‑phase or ongoing studies, and may evolve with additional follow‑up and peer‑reviewed publication.

Last updated: Oct 2025