Evorpacept plus trastuzumab and chemotherapy for metastatic HER2‑positive breast cancer after trastuzumab‑deruxtecan

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a Phase 2, single‑arm, multicenter substudy testing the combination of evorpacept with trastuzumab and a physician‑chosen chemotherapy in patients with HER2‑positive metastatic breast cancer previously treated with trastuzumab‑deruxtecan. The trial measures antitumor activity (using RECIST v1.1) alongside safety and tolerability. Chemotherapy options include capecitabine, eribulin, gemcitabine, paclitaxel, or vinorelbine, and treatment continues until disease progression, unacceptable toxicity, death, participant withdrawal, or sponsor/investigator decision. Participants must have measurable disease, ECOG 0–1, LVEF ≥50%, and adequate organ function to enroll.

Why it matters

Who can join: the full rules

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:

  * 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.

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:

  1. 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.
  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 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.

Where it's running

• Mayo Clinic Building-Phoenix
  Phoenix, Arizona, United States Recruiting
• The University of Arizona Cancer Center - North Campus
  Tucson, Arizona, United States Recruiting
• City of Hope
  Duarte, California, United States Recruiting
• UC San Diego Moores Cancer Center
  La Jolla, California, United States Recruiting
• UC Irvine Health - Chao Family Comprehensive Cancer Center
  Orange, California, United States Recruiting
• Lutheran Hospital - Cancer Centers of Colorado
  Golden, Colorado, United States Recruiting

+11 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: Cheng Quah, MD
• Email: info@alxoncology.com
• Phone: 650-466-7125

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.