IMM27M, a humanized Fc-engineered anti CTLA-4 antibody, in patients with advanced solid tumors: A phase I dose-escalation and dose-expansion study.

e13061 Background: IMM27M is a humanized Fc-engineered IgG1 CTLA-4 monoclonal antibody with enhanced ADCC. In pre-clinical models, IMM27M enhanced immune responses and promote Treg depletion. The pre-clinical results showed IMM27M induced significantly stronger anti-tumor activity than ipilimumab and resulted in complete tumor remission even at a low dose. In dose-escalation stage, 25 patients (pts) (20 females, 5 males) were enrolled and treated Treatment-related adverse events (TRAEs) occurred in 24 pts (96.0%). Most TRAEs (92.2%) were grade 1 or 2. Among 25 efficacy-evaluable pts, 2 pts had confirmed PR. The recommended Phase 2 Dose (RP2D) was determined as 5 mg/kg. At 5 mg/kg level (N = 7), 6-month PFS rate per RECIST 1.1 was 34.3% with median follow-up 5.9 months. Methods: This study is a phase I, open-label, multi-center study to evaluate the safety, tolerability, maximum tolerated dose/recommended dose for expansion, PK and anti-tumor activity in patients with advanced solid tumors. 5mg/kg Q3W was selected for cohort expansion. Advanced HR positive/HER2 negative Breast Cancer (BC) and Hepatocellular Carcinoma (HCC) with standard treatment failure were enrolled. Primary endpoint was safety and secondary endpoint was investigator assessed ORR. Here we report updated results in cohort expansion (NCT05235438). Results: As of 20 Dec 2024, 17 patients (pts) were enrolled and dosed at 5 mg/kg, including 11 HR + /HER2 - mBC and 6 HCC. The medium age was 50 and all patients were ECOG PS 0-1. All pts previously received ≥ 2 lines of systemic therapies and 6 out of 17 were previously treated with IO. Treatment-related adverse events (TRAEs) occurred in 16 pts (94.1%). Most TRAEs (92.9%) were grade 1 or 2. The most common TRAEs (≥5%) of all grades were hypoalbuminemia (8.7%) and fever (4.9%). Grade ≥3 TRAEs occurred in 8 pts (47%). No TRAE led to treatment discontinuation. No TEAE led to death was reported. In 7 efficacy evaluable HR + /HER2 - mBC pts, 3 pts were SD, of which 2 SD with tumor shrinkage over 10%. In 4 efficacy-evaluable HCC pts, 2 pts were SD, including 1 had SD with tumor shrinkage over 10%. The enrollment is ongoing. Conclusions: IMM27M monotherapy was well-tolerated, with preliminarily single agent activity could be seen in patients with late line advanced solid tumors especially with HR + /HER2 - mBC. Clinical trial information: NCT05235438 .