Protocol ASPEN-09-03: A Single-arm Phase 2 Multicenter Study of Evorpacept in Combination With Trastuzumab and Chemotherapy in Participants With Metastatic HER2-Positive Breast Cancer, a Substudy Under Master Protocol ASPEN-09: A Phase 1b/2, Multicenter, Multi Arm Study of Evorpacept in Combination With Anti-cancer Therapies in Advanced / Metastatic Malignancies
The Substudy Protocol ASPEN-09-03 is a Phase 2, single-arm, multicenter study 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. ASPEN-09-03 is a substudy under Master Protocol ASPEN-09, and additional substudies are as follows: * Metastatic colorectal cancer (CRC) - dose escalation phase to evaluate evorpacept in combination with other drugs. This substudy is not open. * Recurrent/metastatic head and neck cancer (HNSCC) - dose escalation phase to evaluate evorpacept in combination with other drugs. This substudy is not open.
• Histologically confirmed invasive HER2+ breast cancer.
• Received at least one prior line of therapy including T-DXd (ENHERTU) for locally advanced/metastatic HER2+ 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. Participants who discontinue T-DXd due to intolerance are considered eligible.
• 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).
• Measurable disease as defined by RECIST v1.1.
• LVEF ≥50%.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) must be 0 to 1.
• Life expectancy of at least 3 months.
• Adequate renal function (estimated creatinine clearance ≥30 mL/min as calculated using the Cockcroft-Gault equation or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 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).
• 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 and which do not constitute a safety risk by Investigator judgment.