A first-in-human study of MIL95, an anti-CD47 monoclonal antibody (mAb), in patients with advanced solid tumors and lymphomas.

Abstract

e14513 Background: CD47 provides a potent “do not eat me” signal that allows the tumor to escape removal by the innate immune system. MIL95 is a humanized, anti-CD47 lgG4 monoclonal antibody and that mediated blockade of CD47 can induce macrophage phagocytosis of cancer cells. To evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and antitumor activity of MIL95, we conducted a first-in-human phase 1 trial in pts with advanced solid tumors and lymphomas (Protocol number MIL95-CT101, Beijing Mabworks Biotech Co. Ltd.) at 5 clinical study sites in China. Currently the study is still ongoing. Methods: We enrolled pts aged 18 years or older with advanced solid tumors and lymphomas whose disease had progressed after standard systemic treatments. Pts were required to ECOG PS score of 0-1 and adequate organ functions. Pts were enrolled in this two-part dose-escalation study: Part A, to determine a priming dose at 0.1, 0.3, 0.8, 1 mg/kg; Part B, to determine optimal weekly maintenance dose at 3, 10, 20, 30, 45 mg/kg. Dose escalation was performed using an accelerated titration followed by traditional 3+3 design during a 14-day (Part A) or 28-day (Part B) dose-limiting toxicity (DLT) observation period. Results: As of 18 Dec 2022, 24 pts (median age 54.5 years; 37.5% male; 54.2% ECOG PS 1) were treated: 8 in part A, 16 in part B. The common tumor types were lymphomas (25.0%) and breast (25.0%), lung (12.5%) cancers. MIL95 toxicity was manageable, no DLT was observed, and dose escalation was ongoing at 45mg/kg. The most common treatment-related adverse events (TRAEs) occurring in ≥10% of pts were anemia (37.5%), blood bilirubin increased (37.5%), leukopenia (20.8%), pyrexia (16.7%), and fatigue (16.7%). Most toxicities were Grade 1 or 2. Five pts had ≥Grade 3 TRAEs (Grade 3 anemia in 2 pts, Grade 3 decreased appetite in 1 pt, Grade 3 enteritis infectious in 1 pt, Grade 4 platelet count decreased in 1 pt). 4 pts had SD as a best response, with 1 pt (Cholangiocarcinoma at dose 20 mg/kg) on study for >5 months. Conclusions: MIL95 was well tolerated at 1 mg/kg priming dose following by maintenance doses of up to 45 mg/kg weekly. Further antitumor activity may need to be combined with other therapies. Clinical trial information: NCT04651348 .