A phase 2, multiarm study of anti-CD47 antibody, magrolimab, in combination with docetaxel in patients with locally advanced or metastatic solid tumors.

Authors

Vivek Subbiah

Vivek Subbiah

Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX

Vivek Subbiah , Ulka N. Vaishampayan , Sonam Puri , Lanjia Lin , Mark Chao , Giri Ramsingh , Shivaani Kummar , James F. Strauss , Sandip P. Patel

Organizations

Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, Huntsman Cancer Center at the University of Utah, Salt Lake City, UT, Gilead Sciences, Inc., Foster City, CA, Oregon Health and Science University, Portland, OR, Mary Crowley Cancer Research Center, Dallas, TX, University of California San Diego, San Diego, CA

Research Funding

Pharmaceutical/Biotech Company

Background: Patients with solid tumors who progress on standard chemotherapy and/or immune checkpoint inhibitors have limited efficacy with existing standard-of-care chemotherapy options (objective response rates [ORRs] ̃10%). These patients have a significant unmet medical need. Novel agents that can safely enhance treatment efficacy are urgently needed. Magrolimab is a first-in-class monoclonal antibody that blocks the macrophage inhibitory immune checkpoint CD47, a “do not eat me” signal overexpressed on tumor cells. Preclinical studies provide compelling evidence that magrolimab triggers phagocytosis and eliminates cancer cells from human solid tumors and hematologic malignancies. Magrolimab has demonstrated clinical activity in both hematologic and solid tumor malignancies. Chemotherapeutic agents, including taxanes, enhance prophagocytic signals on tumor cells, leading to synergistic antitumor activity when combined with magrolimab. This study (NCT04827576) is evaluating the safety, tolerability, and efficacy of magrolimab with docetaxel in relapsed/refractory (R/R) metastatic urothelial cancer (mUC), non-small-cell lung cancer (mNSCLC), and small-cell lung cancer (mSCLC). Methods: This Phase 2, open-label, multi-arm study (NCT04827576) consists of a safety run-in cohort and a Phase 2 cohort. Eligible patients are ≥18 years old with chemotherapy- and/or immunotherapy-refractory mUC, mNSCLC, or mSCLC. Magrolimab is administered intravenously (IV) with an initial 1-mg/kg priming dose to mitigate on-target anemia, followed by a 30-mg/kg dose during cycle 1 (cycles are 21 days) in the safety run-in to identify any dose-limiting toxicities (DLTs) and determine a recommended Phase 2 dose (RP2D). De-escalation may occur for DLTs per protocol. In Phase 2, following the priming dose on day 1, the highest acceptable dose of magrolimab will be administered on days 8 and 15 of cycle 1; days 1, 8, and 15 of cycle 2; and day 1 for cycles 3 and beyond. Docetaxel 75 mg/m2 is administered IV on day 1 of each cycle for all study participants. Patients may continue treatment until unacceptable toxicity, progressive disease by RECIST 1.1, or patient/investigator choice to discontinue. The primary endpoints are incidence of adverse events (safety and Phase 2 cohorts) and ORR (Phase 2). Secondary endpoints (Phase 2) are progression-free survival, duration of response, and overall survival. Exploratory endpoints are to evaluate the pharmacodynamic, mechanism of action, and/or therapeutic response of biomarkers in blood and tumor biopsy samples and to explore biomarkers that may predict response to therapy. Enrollment began in August 2021. Planned enrollment is approximately 116 patients, and as of October 1, 2021 recruitment is ongoing. Clinical trial information: NCT04827576.

Disclaimer

This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org

Abstract Details

Meeting

2022 ASCO Genitourinary Cancers Symposium

Session Type

Trials in Progress Poster Session

Session Title

Trials in Progress Poster Session B: Urothelial Carcinoma

Track

Urothelial Carcinoma

Sub Track

Therapeutics

Clinical Trial Registration Number

NCT04827576

Citation

J Clin Oncol 40, 2022 (suppl 6; abstr TPS584)

DOI

10.1200/JCO.2022.40.6_suppl.TPS584

Abstract #

TPS584

Poster Bd #

N6

Abstract Disclosures