Abstract CT173: Preliminary results from a phase I study of IMM0306 in patients with relapsed or refractory CD20-positive B-cell non-Hodgkin's lymphoma
Authors: Shi Yuankai , Yang Jianliang , Song Yongping , Zhou Keshu , Li Zhiming , Zhang Mingzhi , Jing Hongmei , Wang Zhen , Yu Li , Lu Qiying , Gan Frank , Tian Wenzhi 
Published: April 2024

Background: IMM0306 is a fusion protein of CD20 monoclonal antibody with the CD47 binding domain of SIRPα on both heavy chains. It exerts excellent cancer killing efficacy by activating both macrophages and NK cells via blockade of CD47-SIRPα interaction and FcɣR engagement. Here, we report the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy results of phase I in patients (pts) with relapsed or refractory (R/R) CD20-positive B-cell non-Hodgkin's lymphoma (B-NHL).

Methods: Eligible pts with R/R CD20-positive B-NHL were enrolled in this open-label, multicenter phase I/II study (NCT05805943). IMM0306 was administered as monotherapy at escalating doses of 0.04, 0.1, 0.25, 0.5, 0.8, 1.2, 1.6, 2.0 mg/kg intravenously once a week after a 2-week single-dose observation period, until disease progression or intolerable toxicity. Dose-limiting toxicity (DLT) was evaluated in the first 28 days. Safety was evaluated per CTCAE 5.0, PK and PD analysis were also assessed, tumor assessments performed once every 8 weeks by Lugano 2014.

Results: As of Nov 21, 2023, 48 pts were enrolled. The median age was 56 years with 30 (62.5%) males. The median prior lines of therapy was 2. All pts received previous anti-CD20 therapy. No DLTs were observed. Recommended phase II dose (RP2D) was determined as 2.0 mg/kg. The most frequent treatment related adverse events (TRAEs) were WBC decreased (66.7%), anemia (64.6%), lymphocyte decreased (58.3%), ANC decreased (47.9%), PLT decreased (45.8%), infusion-related reactions (35.4%). Grade ≥3 TRAEs occurred in 33 (68.8%) pts, the most frequent grade ≥ 3 TRAEs were lymphocyte decreased (56.3%), WBC decreased (18.8%), ANC decreased (18.8%). Eight (16.7%) pts experienced treatment related serious adverse event, including PLT decreased, chest pain and pneumonia. Drug discontinuation due to AEs occurred in 1 pt (G4 PLT decreased occurred at 1.6mg/kg without any bleeding). No AE led to death. IMM0306 exhibited approximate dose-proportional increase in PK exposure from 0.5 to 2.0 mg/kg and no obvious accumulation was observed after repeated dosing. At 1.2 mg/kg, CD47 receptor occupancy on peripheral lymphocytes was saturated, suggesting IMM0306 is well tolerated from perspective of CD47 engagement in high dose cohorts. B-cell counts depleted rapidly at doses ≥ 0.8 mg/kg. Elevated cytokines levels were observed after first dosing of IMM0306, but multiple dosing did not stimulate further cytokine activation. Among 33 pts who received active doses ≥ 0.8 mg/kg, 5 CR (4 follicular lymphoma [FL], 1 marginal zone lymphoma [MZL]), 5 PR (3 FL, 1 MZL, 1 diffuse large B cell lymphoma) and 11 SD were seen. Among 17 FL pts, 7 (41%) responded including 4 CR and 3 PR; among 6 MZL pts, 2 (33.3%) responded including 1 CR and 1 PR.

Conclusions: IMM0306 was well-tolerated and with a robust preliminary anti-tumor activity especially in pts with R/R FL and MZL. The phase II study is ongoing.

Citation Format: Yuankai Shi, Jianliang Yang, Yongping Song, Keshu Zhou, Zhiming Li, Mingzhi Zhang, Hongmei Jing, Zhen Wang, Li Yu, Qiying Lu, Frank Gan, Wenzhi Tian. Preliminary results from a phase I study of IMM0306 in patients with relapsed or refractory CD20-positive B-cell non-Hodgkin's lymphoma [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(7_Suppl):Abstract nr CT173.