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

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

Phase 2 Interventional ALX Oncology Inc. · NCT07007559

This trial will test whether adding evorpacept to trastuzumab and chemotherapy helps people with metastatic HER2‑positive breast cancer whose disease progressed after trastuzumab‑deruxtecan.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment120 (estimated)
Ages18 Years and up
SexAll
SponsorALX Oncology Inc. Industry-sponsored
Drugs / interventionstrastuzumab, chemotherapy, radiation
Locations32 sites (Tucson, Arizona and 31 other locations)
Trial IDNCT07007559 on ClinicalTrials.gov

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.

Who should consider this trial

Good fit: Adults with histologically confirmed HER2‑positive metastatic breast cancer who have received at least one prior line including trastuzumab‑deruxtecan, have measurable disease, ECOG performance status 0–1, LVEF ≥50%, and adequate organ function to receive one of the allowed chemotherapies.

Not a fit: Patients who cannot tolerate chemotherapy, have poor performance status (ECOG >1), significant cardiac dysfunction (LVEF <50%), or a life expectancy under three months are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this combination could offer a new treatment option that controls disease or produces responses for patients whose cancer progressed after trastuzumab‑deruxtecan.

How similar studies have performed: Early‑phase trials of CD47‑pathway inhibitors like evorpacept combined with other anticancer agents have shown some encouraging signals in various tumors, but this exact combination in post‑T‑Dxd HER2+ breast cancer remains largely untested.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* 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.

Exclusion Criteria:

* Participants with known CNS metastases unless treated and stable prior to enrollment.
* 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 this trial is running

Tucson, Arizona and 31 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Breast Cancer, MetastaticmetastaticHer2+metastatic HER2-positive breast cancerbreast cancerHER2-positiveEvorpaceptCD47
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.