First-in-human phase 1 study of TQB6411, an EGFR/c-Met bispecific antibody-drug conjugate (ADC), in patients with advanced solid tumors.

Abstract

3032 Background: EGFR and c-Met overexpression are common across various solid tumors. TQB6411 is a novel ADC binding to both EGFR and c-Met with a valency of 1:2 to enhance the affinity to c-Met. Here we report the preliminary results of this first-in-human phase 1 study of TQB6411(NCT07043751). Methods: Patients (pts) with advanced malignant tumor who had failed or were intolerant to standard treatment were eligible. TQB6411 was administered intravenously once every 3 weeks. An accelerated titration design was used for the initial dose level (0.8 mg/kg), followed by a conventional 3+3 dose escalation design for the remaining dose levels. The primary endpoints were dose-limiting toxicity (DLT), recommended phase II dose and safety. Results: As of December 31, 2025, 26 pts were enrolled and received research treatment (median age [range], 60[33–75] years; 46.2% female). The most common diagnosis was non-small cell lung cancer (NSCLC, 21 pts), followed by esophageal cancer (EC, 3 pts) and colorectal cancer (CC, 2 pts). All pts had received at least one previous line of systemic treatment. Dose group assignments were as follows: 1 in 0.8mg/kg, 3 in 2.4mg/kg, 13 in 4mg/kg, 6 in 5.3mg/kg, and 3 in 6.6mg/kg. By the data cutoff date of January 9, 2026, the dose had been escalated to 6.6mg/kg, with no DLT occurring. The median treatment duration was 3 cycles (rang:1-9). In 22 pts who were followed up for at least 21 days, 19 (86.4%) experienced at least 1 treatment-related adverse event (TRAE). The most common TRAEs included asthenia (54.5%), infusion reaction (50.0%, decreasing to 38.9% in the ≥4 mg/kg dose group after prophylaxis modification), myalgia (27.3%), alopecia (22.7%), and neutrophil count decreased (22.7%). No interstitial lung disease occurred. Only 4 cases of grade 3 AEs (two of neutrophil count decreased, one of allergic shock, one of white blood cell count decreased) were observed in 3 pts and were all attributed to TQB6411. No ≥ grade 4 AEs occurred. In the ≥4 mg/kg dose group, 8 pts received at least one imaging assessment, 4 achieved a partial response (PR), giving an objective response rate of 50.0%. The disease control rate was 100%. The details of efficacy results are shown in the table below. Conclusions: In this ongoing phase 1 study. TQB6411 showed an impressive safety profile, with a lower incidence of higher-grade TRAEs (especially lower haematological toxicities), and encouraging efficacy, with tumor responses could be observed even in the relatively lower dose group. Clinical trial information: NCT07043751 . 4mg/kg (N = 6) 5.3mg/kg (N=2) PR, n 3 (NSCLC: 2, EC:1) 1(NSCLC) SD, n 3 (NSCLC) 1 (NSCLC)