Safety and efficacy of amulirafusp alfa (IMM0306), a fusion protein of CD20 monoclonal antibody with the CD47 binding domain of SIRPα, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a phase 1/2 study

  • J Hematol Oncol. 2024 Dec 18;17(1):123. doi: 10.1186/s13045-024-01646-2.
Jianliang Yang  1 ,  Yongping Song  2 ,  Keshu Zhou  2 ,  Zhiming Li  3 ,  Mingzhi Zhang  4 ,  Hongmei Jing  5 ,  Zhen Wang  6 ,  Li Yu  7 ,  Wei Meng  8 ,  Qiying Lu  8 ,  Wenzhi Tian  8 ,  Yuankai Shi  9
Affiliations
  • 1. Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.
  • 2. Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
  • 3. Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
  • 4. Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 5. Department of Hematology, Peking University Third Hospital, Beijing, China.
  • 6. Department of Medical Oncology, Linyi Cancer Hospital, Linyi, China.
  • 7. Department of Hematology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
  • 8. ImmuneOnco Biopharmaceuticals (Shanghai) Inc., Shanghai, China.
  • 9. Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China. [email protected].
PMID: 39696680 DOI: 10.1186/s13045-024-01646-2
Abstract

Background: Amulirafusp alfa (IMM0306) is a fusion protein of CD47 binding domain of signal-regulatory protein alpha (SIRPα) with CD20 monoclonal antibody on both heavy chains. This study aimed to evaluate the safety and preliminary efficacy of amulirafusp alfa in relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL).

Methods: We enrolled patients with CD20 + r/r B-NHL who had previously received at least two lines of therapy to receive a single-dose of amulirafusp alfa in the first 2 weeks, followed by a multiple-dose period, in which the patients received the same intravenous dose every week in 4-week cycles. The primary endpoints were to evaluate the safety, determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of amulirafusp alfa.

Results: Between May 22, 2020 and February 10, 2022, 48 patients with r/r B-NHL were enrolled and received amulirafusp alfa at the doses of 40-2000 μg/kg. As of the data cut-off date of April 18, 2024, no dose-limiting toxicity was observed, and the MTD was not reached. The dose of 2000 μg/kg was identified as the RP2D. All grades and ≥ grade 3 treatment-related adverse events (TRAEs) occurred in 48 (100%) and 33 (68.8%) patients, respectively. The most common ≥ grade 3 TRAEs were lymphocyte count decreased (28/48, 58.3%), white blood cell count decreased (10/48, 20.8%), absolute neutrophil count decreased (9/48, 18.8%) and anemia (5/48, 10.4%). At the doses of 800-2000 μg/kg, objective response rate in follicular lymphoma and marginal zone lymphoma was 41.2% (7/17, 95% confidence interval [CI] 18.4-67.1) and 33.3% (2/6, 95% CI 3.7-71.0), respectively.

Conclusion: Amulirafusp alfa showed favorable safety profile and preliminary efficacy in patients with r/r B-NHL, meriting further investigation. Trial registration NCT05805943.

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