A Phase 1b / 2, Multicenter, Multi Arm Study of Evorpacept in Combination with Anti-cancer Therapies in Advanced / Metastatic Malignancies
* Metastatic HER2+ breast cancer (MBC) - single-arm substudy evaluating the efficacy, safety, and tolerability of evorpacept in combination with trastuzumab and chemotherapy in participants with HER2-positive metastatic breast cancer who have previously received trastuzumab-deruxtecan. This substudy is actively recruiting.
* Metastatic colorectal cancer (CRC) - dose escalation phase to evaluate evorpacept in combination with other drugs. This substudy is not recruiting.
* Recurrent/metastatic head and neck cancer (HNSCC) - dose escalation phase to evaluate evorpacept in combination with other drugs. This substudy is not recruiting.
Eligibility: 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-SIRP¿ 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