Abstract OT2-10-01: A phase 2, randomized study of magrolimab combination therapy in adult patients with unresectable locally advanced or metastatic triple-negative breast cancer
Authors: Rainey Natalie , Joshi Rohit , Chiu Joanne Win Yang , Chen Ann , Wang Hao , Odegard Jared , Howland Michael , Adams Sylvia 
Published: March 2023

Abstract
Background: Improving outcomes for patients (pts) with triple-negative breast cancer (TNBC) remains a high unmet need. Immune checkpoint inhibitors (ICIs) + chemotherapy (chemo) and single-agent sacituzumab govitecan, a trophoblast cell-surface antigen 2–targeted antibody-drug conjugate coupled to SN38 via a proprietary, hydrolysable linker, are approved in newly diagnosed pts with programmed death-ligand 1 (PD-L1)–positive tumors and pts who received ≥2 prior systemic therapies (≥1 for metastatic disease), respectively. However, additional options are urgently needed, particularly for pts with tumors that do not express PD-L1 and for those with progression on chemo ± ICI. Magrolimab is an antibody blocking CD47, a “don’t eat me” signal overexpressed on cancer cells, including TNBC, inducing tumor phagocytosis by macrophages. Magrolimab has shown preclinical activity and promising clinical efficacy in hematologic and solid tumors. Chemo agents, including taxanes, can enhance prophagocytic signals on tumor cells, leading to the potential for synergistic antitumor activity with magrolimab. This study is evaluating the safety/tolerability and efficacy of magrolimab in combination with nab-paclitaxel/paclitaxel or with sacituzumab govitecan in unresectable locally advanced/metastatic TNBC. Trial Design: This open-label, 2-cohort (C) study consists of safety run-in and phase (ph)2 portions evaluating nab-paclitaxel/paclitaxel (choice) + magrolimab (safety run-in) or ± magrolimab (ph2, randomized 1:1) in pts with untreated, advanced/metastatic TNBC ineligible for ICI (C1) and magrolimab + sacituzumab govitecan (safety run-in and ph2) in pts with advanced TNBC who received 1 prior systemic treatment in the metastatic setting (C2). Stratification factors for C1 are neoadjuvant and/or adjuvant taxane therapy, liver metastases, and nab-paclitaxel vs paclitaxel. In both cohorts, magrolimab will be administered intravenously (IV) in de-escalating doses to establish the recommended ph2 dose (RP2D). Nab-paclitaxel/paclitaxel and sacituzumab govitecan will be administered IV per standard of care. Eligibility Criteria: Eligible pts are ≥18 y with PD-L1–negative, untreated, unresectable locally advanced/metastatic TNBC (C1) or unresectable locally advanced/metastatic TNBC who received 1 prior line of therapy in the advanced setting, including a taxane and an ICI if PD-L1 positive (C2), with measurable disease per RECIST v1.1. Exclusion criteria include active central nervous system disease, red blood cell transfusion dependence, or prior treatment with CD47/signal regulatory protein α–targeting agents for both cohorts. Additional exclusions are disease progression within 6 months of (neo)adjuvant therapy or rapid visceral progression and/or symptomatic disease, for which single-agent chemo would not be appropriate (C1); chronic inflammatory bowel disease and a history of bowel obstruction or gastrointestinal perforation within 6 months of enrollment, prior treatment with topoisomerase I inhibitors or antibody-drug conjugates containing a topoisomerase inhibitor, and receipt of high-dose systemic corticosteroids within 2 weeks of cycle 1 day 1 (C2). Specific Aims: The primary objectives are safety/tolerability and magrolimab RP2D (safety run-in) and efficacy (ph2: C1, progression-free survival [PFS]; C2, objective response rate [ORR]; both by investigator). Secondary objectives include ORR, PFS, and duration of response by investigator and independent central review, overall survival, and magrolimab concentration vs time and antidrug antibodies. Present and Target Accrual: The study is enrolling in the US, Australia, and Hong Kong. Target accrual is 144 pts. Contact Information: ClinicalTrials.gov: NCT04958785.
Citation Format: Natalie Rainey, Rohit Joshi, Joanne Win Yang Chiu, Ann Chen, Hao Wang, Jared Odegard, Michael Howland, Sylvia Adams. A phase 2, randomized study of magrolimab combination therapy in adult patients with unresectable locally advanced or metastatic triple-negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-10-01.