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.