Phase 1 basket study of telisotuzumab adizutecan (Temab-A, ABBV-400), a c-Met protein–targeting antibody-drug conjugate: Results from patients with head and neck squamous cell carcinoma (HNSCC).

Abstract

6027 Background: c-Met protein is expressed in several tumor types, including HNSCC, and is associated with a poor prognosis. Temab-A comprises a c-Met protein-targeting antibody conjugated to a topoisomerase 1 inhibitor. Phase 1 studies evaluating Temab-A monotherapy in solid tumors showed antitumor activity and a manageable safety profile (NCT05029882, NCT06084481). Here, we report on the efficacy and safety of Temab-A in HNSCC. Methods: This phase 1, open-label basket study (NCT06084481) enrolled patients (pts) ≥18 years with histologically/cytologically confirmed locally advanced or recurrent/metastatic, unresectable HNSCC, with Eastern Cooperative Oncology Group performance score ≤1. Pts must have had measurable disease per RECIST v1.1 criteria, and disease progression following ≥1 line of systemic therapy in the advanced/metastatic setting. Pts were platinum-resistant or deemed ineligible/unfit for platinum-based therapy per investigator. Prior checkpoint inhibitor treatment was required, unless contraindicated. Pts received 2.4 or 3.0 mg/kg Temab-A every 3 weeks. Primary objectives were safety and efficacy. Results: As of Sept. 11, 2025, 43 pts with HNSCC received Temab-A. The median age was 64 years (range 20–85). Median number of prior lines of systemic therapy was 3 (range 1–12), and median follow-up was 12 months. Objective response rate (ORR) was 21%; duration of response and overall survival were immature at data cutoff. Efficacy data are shown in the Table. The most common treatment-related adverse events (TRAEs) of any Grade (G) included fatigue (51%), anemia (49%), and nausea (40%). TRAEs G ≥3 occurred in 47% of pts. G ≥3 TRAE occurring in ≥10% of pts was anemia (33%). The adjudicated interstitial lung disease/pneumonitis rate was 9.3% (G1, n=2; G2, n=1; G3, n=1). TRAEs led to treatment discontinuation in 12%, dose interruption in 30%, and dose reduction in 26% of pts. There was 1 TRAE that led to death. Exploratory biomarker analyses are ongoing. Pharmacokinetics of Temab-A in HNSCC were consistent with other tumor types. The half-life of the conjugate and payload was 4 and 13 days, respectively. Conclusions: Temab-A had a manageable safety profile and showed encouraging antitumor activity in advanced HNSCC. Clinical trial information: NCT06084481 . Temab-A efficacy. a Outcome Pts with HNSCC (N=43) Best overall response, n (%)Complete responsePartial responseStable diseaseProgressive diseaseNot assessed b 011 (26)22 (51)7 (16)3 (7) Objective response rate c , n (%)95% CI 9 (21)10, 36 Clinical benefit rate c , n (%)95% CI 33 (77)61, 88 Median progression-free survival, months (95% CI) 4.3 (3.8, 5.4) a Responses were assessed by investigators per RECIST v1.1 criteria. b Pts without postbaseline scan. c Confirmed. CI, confidence interval.