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

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