Background: Patients with solid tumors who progress on chemotherapy and/or immune-checkpoint inhibitors experience limited efficacy with existing standard of care options (objective response rates [ORR] ∼10%), so novel agents that can safely enhance efficacy are 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 suggest 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) evaluates the safety, tolerability, and efficacy of magrolimab with docetaxel in relapsed/refractory 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 consists of safety run-in and Phase 2 cohorts. Patients are ≥18 years 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 30 mg/kg dose during Cycle 1 (cycles are 21 days) in the safety run-in to identify 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, magrolimab RP2D 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 IV is administered on Day 1 of each cycle. Treatment may continue until unacceptable toxicity, progressive disease, or patient/investigator choice. 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 evaluate the pharmacodynamic, mechanism of action, and/or therapeutic response of biomarkers and explore biomarkers that may predict response to therapy. Planned recruitment is ∼116 patients, and as of October 2021, 3 study sites are active (all in U.S.).