Clinical Trial 24222

• Overview

  Study Title:

  A Phase 1b / 2, Multicenter, Multi Arm Study of Evorpacept in Combination with Anti-cancer Therapies in Advanced / Metastatic Malignancies (ASPEN-09) Substudy 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 (ASPEN-09-03)

  Summary:

  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.

  Objective:

  Primary Objective: * To evaluate the overall response rate of evorpacept in combination with trastuzumab and single agent chemotherapy in the sub-population of participants with metastatic HER2+ BC who express CD47 (CD47+), by level of CD47 expression. Secondary Objectives: * To assess secondary measures of efficacy for evorpacept administered in combination with trastuzumab and chemotherapy in the sub-population of participants with metastatic HER2+ BC who express CD47 (CD47+), by level of CD47 expression. * To evaluate the efficacy of evorpacept administered in combination with trastuzumab and chemotherapy in the sub-population of participants with metastatic HER2+ BC who have HER2 (ERBB2) copy number amplification in ctDNA at baseline (ctDNA+) by level of CD47 expression. * To evaluate the efficacy of evorpacept administered in combination with trastuzumab and chemotherapy in the sub-population of participants with metastatic centrally assessed HER2+, CD47+ BC by level of CD47 expression. * To evaluate the safety profile of evorpacept in combination with trastuzumab and each of the chemotherapy agents. * To characterize the PK of evorpacept in combination with trastuzumab and chemotherapy. * To evaluate the immunogenicity of evorpacept.

• Treatments

  Therapies:

  Chemotheraphy; Immunotherapy; Protein-based therapeutic acting as a myeloid immune checkpoint inhibitor

  Medications:

  Eribulin (); Evorpacept (); Gemzar (gemcitabine); Herceptin (Trastuzumab); Navelbine (Vinorelbine); Taxol (paclitaxel); Trastuzumab (); Vinorelbine (); Xeloda (capecitabine); capecitabine (); gemcitabine (); paclitaxel (); rhuMAb HER2 (Trastuzumab)

• Inclusion Criteria

  Key Inclusion Criteria:
  • Histologically confirmed invasive HER2+ breast cancer based on an evaluable tumor tissue biopsy obtained after cessation of T-DXd (ENHERTU) treatment and no more than 6 months prior to C1D1.
  • Received no more than 4 prior lines of HER2-directed therapy including at least one prior line of 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.
  • 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.

• Exclusion Criteria

  Key Exclusion Criteria:
  • Untreated CNS metastases.
  • Prior exposure to any anti-CD47 or anti-SIRPα agent.
  • Any condition that would be contraindicated to receiving trastuzumab.
  • Has a diagnosis of complete dihydropyrimidine dehydrogenase (DPD) deficiency or significant toxicity with prior flurouracil (5FU) based regimen.
  • Following anti-cancer therapy with insufficient washout before start of treatment: Chemotherapy, hormonal therapy, radiation therapy or small molecule anti-cancer therapy within 14 days or 5 half-lives (whichever is shorter) of start of treatment. 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 start of treatment).
  • 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.
  • Other primary malignancy within 2 years.

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