ASPEN-09: A Study of Evorpacept in Combination With Anti-cancer Therapies in Advanced / Metastatic Malignancies

Inclusion Criteria

• Inclusion Criteria (all substudies): - Participants must have at least one measurable lesion as defined by RECIST v1.1. - Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) must be 0 to 1. - Life expectancy of at least 3 months - Participants must have recovered from all AEs due to previous therapies, procedures, and surgeries to baseline severity or ≤Grade 1 per NCI CTCAE v5.0 except for AEs not deemed reversible which do not constitute a safety risk by Investigator judgment MBC substudy: - Histologically confirmed invasive HER2 positive breast cancer - Available tumor tissue (FFPE slides or block). A fresh biopsy is preferred but optional. - Received at least one prior line of therapy including T-DXd for locally advanced/metastatic HER2 positive breast cancer. Prior neoadjuvant therapy which resulted in relapse within 6 months of completion of T-DXd will be considered a line of treatment for metastatic disease. - Progressed on or following the most recent line of therapy - Eligible to receive one of the following chemotherapy options (capecitabine, eribulin, gemcitabine, paclitaxel or vinorelbine) - LVEF ≥50% - Adequate renal function (estimated creatinine clearance ≥30 mL/min as calculated using the Cockroft-Gault equation - Adequate liver function: - Total bilirubin ≤1.5 x upper limit of normal (ULN) (≤3.0 x ULN if the participant has documented Gilbert syndrome); - Aspartate and alanine transaminase (AST and ALT) ≤3 x ULN (≤5.0 x ULN if liver involved by metastatic disease). Exclusion Criteria (all substudies): - Participants with known CNS metastases unless treated and stable prior to enrollment - Following anti-cancer therapy with insufficient washout before C1D1: 1. chemotherapy, hormonal therapy, radiation therapy or small molecule anti-cancer therapy within 14 days or 5 half-lives (whichever is shorter) of C1D1. 2. Immune therapy or other biologic therapy (e.g., monoclonal antibodies, antibody-drug conjugates) for the treatment of cancer for: 28 days or 5 half-lives (whichever is shorter) of C1D1) - Prior exposure to any anti-CD47 or anti-SIRPα agent. - History of autoimmune hemolytic anemia, autoimmune thrombocytopenia, or hemolytic transfusion reaction. - Had an allogeneic tissue/solid organ transplant. - Any active, unstable cardiovascular disease - Intolerance to or who have had a severe allergic or anaphylactic reaction to antibodies or infused therapeutic proteins or participants who have had a severe allergic or anaphylactic reaction to any of the substances included in the study drug (including excipients). - Has an active autoimmune disease that has required systemic treatment in past 2 years MBC substudy: - Has a diagnosis of complete dihydropyrimidine dehydrogenase (DPD) deficiency or significant toxicity with prior flurouracil (5FU) based regimen - Other primary malignancy within 2 years - Any condition that would be contraindicated to receiving trastuzumab