A phase 2 multi-arm study of magrolimab in combination with docetaxel in patients with locally advanced or metastatic solid tumors: ELEVATE Lung and UC.
Authors: Subbiah Vivek , Vaishampayan Ulka N. , Puri Sonam , Kummar Shivaani , Perez Julia Martinez , Italiano Antoine , Shao Jiang , Bathia Riya , Sills Aoife , Patel Sandip Pravin 
Published: June 2023

TPS9142 Background: Patients (pts) with solid tumors that progress on standard chemotherapy and/or immune checkpoint inhibitors experience limited efficacy with existing standard of care options. These pts have a significant unmet need, and novel agents that safely enhance treatment efficacy are needed. Magrolimab is a monoclonal antibody that blocks CD47, a "don't eat me" signal often overexpressed on solid tumor cells. Magrolimab blockade of CD47 induces macrophage-mediated phagocytosis of tumor cells and has shown preclinical activity and promising clinical efficacy in hematologic malignancies. Certain chemotherapies, including taxanes, enhance prophagocytic signals on tumor cells, leading to potential synergistic antitumor activity when combined with magrolimab. This study is evaluating the safety, tolerability, and efficacy of magrolimab with docetaxel in metastatic non-small cell lung cancer (mNSCLC), small cell lung cancer (mSCLC), and urothelial cancer (mUC). Methods: This open-label study includes a safety run-in and 3 phase 2 cohorts. Pts eligible for the safety run-in must have had ≥1 (mNSCLC, mSCLC) or 2 and not more than 3 (mUC) prior lines of systemic anticancer therapy in a locally advanced/metastatic setting and will be treated with magrolimab + docetaxel. In phase 2, pts must have either mNSCLC treated with platinum-based chemotherapy and/or an immune checkpoint inhibitor (ICI), mUC treated with prior systemic chemotherapy and/or an ICI, or mSCLC treated with platinum-based chemotherapy with or without an ICI in a locally advanced/metastatic setting. Pts refractory to prior taxane therapy or who have received a taxane within 12 months of study start are excluded. Pts who had prior treatment with CD47/SIRPα-targeting agents were also excluded. Magrolimab is administered intravenously (IV) as a 1-mg/kg priming dose on cycle 1 day 1 (C1 D1) to mitigate on-target anemia followed by 30 mg/kg on D8 and D15. Magrolimab 30 mg/kg is administered on C2 D1, D8, and D15 and 60 mg/kg on D1 for C3+. The recommended phase 2 dose (RP2D) is determined in the safety run-in, with de-escalation if prespecified dose-limiting toxicity criteria are met. Once the RP2D is determined, the phase 2 cohorts will follow the same dose schedule. Docetaxel 75 mg/m2 is administered IV on D1 of each cycle. Reasons for treatment discontinuation may include unacceptable toxicity, disease progression, or pt/investigator choice to discontinue. The primary endpoints are incidence of adverse events by CTCAE v5.0 (safety run-in, phase 2) and investigator-assessed objective response rate by RECIST 1.1 (phase 2 cohorts). Secondary endpoints are magrolimab concentration vs time and antidrug antibodies (safety run-in, phase 2), progression-free survival and duration of response by RECIST 1.1, and overall survival (phase 2 cohorts). Planned enrollment is ≈116 pts. Clinical trial information: NCT04827576 .