918O – Telisotuzumab adizutecan (ABBV-400; Temab-A) in patients with advanced solid tumors harboring MET amplification (MET-amp): results from a phase I study

Telisotuzumab adizutecan (ABBV-400; Temab-A) is an antibody–drug conjugate (ADC) targeting the c-Met (MET) protein, carrying a topoisomerase I inhibitor payload. The c-MET protein is a transmembrane receptor involved in embryonic development and tissue repair; its activation promotes cell growth and protects cells from apoptosis—functions particularly relevant in tumor cells.

Data from the phase I first-in-human (FIH) trial (NCT05029882) show that Temab-A demonstrates promising antitumor activity and a manageable safety profile in patients with advanced solid tumors. Focal amplification of the MET gene (MET-amp) is associated with poor prognosis and resistance to standard therapies, underscoring the need for innovative therapeutic strategies.

Patients with measurable solid tumors (RECIST v1.1) who had progressed after standard treatments were enrolled to receive Temab-A at doses of 1.6, 2.0 (backfill), 2.4, and 3.0 mg/kg every three weeks (Q3W). MET-amp was identified by validated local NGS or FISH tests and centrally confirmed by NGS.

A total of 100 patients were treated, including 29 with non–small cell lung cancer (NSCLC), 22 with colorectal cancer (CRC), 14 with gastroesophageal adenocarcinoma (GEA), and 35 with other tumor types. The median age was 60.5 years (range 23–81); 60% were male, and the median number of prior treatment lines was 2 (range 1–8). Median follow-up was 10.8 months.

The most common treatment-related adverse events (TEAEs) of any grade [≥3] were anemia (60% [40%]), neutropenia (53% [34%]), nausea (56% [1%]), and thrombocytopenia (31% [9%]). Dose reductions or discontinuations occurred in 34% and 14% of patients, respectively (32% and 6% considered Temab-A–related). ILD/pneumonitis occurred in 4% of cases, and six deaths due to causes other than disease progression were reported, none treatment-related.

The confirmed objective response rate (cORR) was 46% across all doses and tumor types, with the highest responses observed in NSCLC (69%) and GEA (71%). The median progression-free survival (PFS) was 9.5 months (95% CI: 5.5–9.2).

These findings suggest that Temab-A monotherapy has a manageable safety profile and encouraging efficacy in patients with advanced MET-amplified solid tumors, supporting further investigation, including in combination regimens.

References:

• Jin Y, Zhang Z, Zou S, et al. A Novel c-MET-Targeting Antibody-Drug Conjugate for Pancreatic Cancer. Front Oncol. 2021;11:634881. doi:10.3389/fonc.2021.634881.
• Study NCT05029882.