Abstract CT097: IMM27M, a humanized Fc-engineered anti CTLA-4 antibody, in patients with advanced solid tumors: A phase I dose-escalation study

Abstract 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 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. 0, 2. 0, 3. 0, 5. 0, 7. 5, 10. 0 mg/kg) was administered as monotherapy Q3W. Results: As of 3 Nov 2023, the dose has been escalated to 7. 5 mg/kg. 25 patients (20 females, 5 males) 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, 4 at 3. 0 mg/kg, 7 at 5. 0 mg/kg, 3 at 7. 5 mg/kg), including 13 patients with breast cancer (10 HR+ mBC), 4 patients with melanoma, 3 patients with RCC, each 1 patient with HCC, NSCLC and ovarian cancer, respectively. Median age was 51 years (range 31-72). 92. 0% of the patients previously received ≥ 2 lines of systemic therapies and 52. 0% received anti PD-1/PD-L1 treatment. Treatment-related adverse events (TRAEs) occurred in 24 patients (96. 0%) by the data cutoff. Most TRAEs were grade 1 or 2. The most common TRAEs (≥ 30%) of all grades were anaemia (56. 0%), lymphocyte count decreased (48. 0%), aspartate aminotransferase increased (40. 0%), hypoalbuminaemia (40. 0%), decreased appetite (40. 0%). Grade ≥3 TRAEs occurred in 11 patients (44. 0%). Grade ≥3 TRAEs (≥10%) were lymphocyte count decreased (16. 0%) and anaemia (12. 0%). Treatment related SAE occurred in 8 patients (32. 0%). No DLT was observed. One TRAE (Grade 3 immune related enteritis) led to treatment discontinuation. No TEAE leading to death was reported. Recommended Phase 2 Dose (RP2D) was 5 mg/kg. In 25 response evaluable patients, 2 patients had confirmed PR: 1 patient with mBC (HR+/HER2+, IO naïve, 6L previous treatments) at 3. 0 mg/kg and response durable for 7 months; 1 patient with mBC (HR+/HER-, IO naïve, 4L previous treatments) at 5. 0 mg/kg and response durable for 3 months by data cut-off. In addition, 9 patients had BOR SD and 4 out of 9 were previously treated with IO. Another 2 out of 8 patients with HR+ mBC had BOR SD with over 10% decreased tumor burden. IMM27M in vivo exposure increased with dose. The T1/2 mean value range in the 3-7. 5mg/kg dose group was 8. 2-11. 5 days. Conclusions: IMM27M monotherapy in general was well-tolerated at the dose levels evaluated and preliminarily single agent activity was seen in patients with heavily pretreated advanced solid tumors. The dose escalation study of IMM27M in advanced solid tumors is ongoing. Clinical trial information: NCT05235438. Citation Format: Shusen Wang, Qiufan Zheng, Quanli Gao, Qingyuan Zhang, Shikai Wu, Zhihua Li, Enxiao Li, Qiying Lu, Frank Gan, Wenzhi Tian. IMM27M, a humanized Fc-engineered anti CTLA-4 antibody, in patients with advanced solid tumors: A phase I dose-escalation study abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (7Suppl): Abstract nr CT097.