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

Abstract

e14670 Background: IMM27M is a humanized Fc-engineered IgG1 CTLA-4 monoclonal antibody with enhanced ADCC. In pre-clinical models, IMM27M could enhance immune responses and promote Treg depletion. The pre-clinical results showed IMM27M induced a significantly stronger anti-tumor activity than ipilimumab and resulted in complete tumor remission even at a low dose. Methods: This study is an open-label, multi-center, phase I dose-escalation study conducted to evaluate the safety, tolerability, maximum tolerated dose/recommended dose for expansion, PK and anti-tumor activity in patients with advanced solid tumors. The study was designed with an accelerated titration followed by a standard 3+3 design. IMM27M (0.1,0.3,1,2,3 mg/kg) was administered as monotherapy on Day 1 of every 3 weeks. Results: As of 30 Dec 2022, the dose has been escalated to 2mg/kg. 11 pts (8 female, 3 male) were enrolled and treated (1 at 0.1 mg/kg, 3 at 0.3 mg/kg, 3 at 1.0 mg/kg, 4 at 2.0 mg/kg), including 3 pts with melanoma, 3 pts with breast carcinoma, 2 pts with RCC, 1 pt with HCC, 1pt with NSCLC and 1 pt with ovarian carcinoma. Median age was 52 years (range 36-72). 9 pts (81.8%) received ≥ 2 lines of previous systemic therapies and 7 pts (63.6%) received previous anti PD-1/PD-L1 treatment. Treatment-related adverse events (TRAEs) occurred in 10 pts (90.9%) to date. Most TRAEs were grade 1 or 2. The most common TRAEs (≥ 10%) of all grades were anaemia (n = 3 [27.3%]), white blood cell count decreased (n = 2 [18.2%]), lymphocyte count decreased (n = 2 [18.2%]), constipation (n = 2 [18.2%]) and rash (n = 2 [18.2%]). Grade ≥3 TRAEs occurred in 2 pts (18.2%): lymphocyte count decreased (G3, n = 1 [9.1%]) and immune-related lung disease (G3, n = 1 [9.1%]). Treatment related SAE patients only occurred in 1 pt (immune-related lung disease, possibly related to treatment), and this patient recovered after clinical treatment. No DLT was observed. No TRAE leading to treatment discontinuation was reported. In 10 response evaluable pts, 3 pts had SD as best response. One pt in 2.0 mg/kg dose cohort had tumor shrinkage of 17% at Week 6, who had metastatic melanoma and received 2 lines of previous treatments including anti PD-1. The treatment of this patient is ongoing. Preliminary PK analysis of IMM27 showed an approximate proportional dose curve and the mean t1/2 was around 11 days. Conclusions: IMM27M monotherapy in general was well-tolerated at the dose level evaluated and preliminarily anti-tumor activity in patients with advanced solid tumors. The dose escalation study of IMM27M in advanced solid tumors is ongoing. Clinical trial information: NCT05235438 .