Trials Today

(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 - HER2 copy number amplified in ctDNA by sponsor's central laboratory - 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). CRC substudy: - Histologically-confirmed left sided metastatic colorectal cancer, confirmed to be pMMR / MSS, KRAS / NRAS / BRAF WT, with tumor tissue available for molecular analysis. - Progression on and after first line oxaliplatin-based standard of care (SOC) therapy for mCRC, with exclusion of an anti-epidermal growth factor receptor (EGFR) treatment. - Adequate renal function - estimated creatinine clearance or glomerular filtration rate ≥60 mL/min as calculated using the Cockroft-Gault equation - Adequate liver function: - Aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase ≤2.5 x upper limit of normal (ULN) with the following exception: - AST and ALT ≤2.5 x ULN; (≤5.0 x ULN if there is liver involvement secondary to tumor due to liver metastasis). - Total bilirubin ≤1.5 x ULN. - Most recent core or incisional biopsy sample prior to study entry, preferably taken after the most recent therapy, should be available for submission

(all substudies): - Participants with known CNS metastases unless treated and stable prior to enrollment - Prior chemotherapy, radiation therapy or small molecule anti-cancer therapy within 14 days or 5 half-lives (whichever is shorter) of C1D1. 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 - Active known second malignancy within 3 years - Other primary malignancy within 2 years - Any condition that would be contraindicated to receiving trastuzumab CRC substudy: - Prior exposure to irinotecan-based therapy or has known toxicity to 5FU and / or irinotecan. - Participants with known Gilberts disease. - Has a diagnosis of known UGT1A1 deficiency. - History of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease. - Prior exposure to anti-EGFR therapies - Diagnosis of immunodeficiency (with the exception of hypogammaglobulinemia) or is receiving chronic systemic steroid therapy or any other form of chronic immunosuppressive therapy within 7 days prior the first dose of study drug.