ASPEN-09-03: A Study of Evorpacept in Combination With Trastuzumab and Chemotherapy in Metastatic HER2-Positive Breast Cancer (ASPEN-09-03)

June 4, 2026 updated by: ALX Oncology Inc.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Participants will continue study treatment until disease progression, death, unacceptable toxicity, participant request to stop treatment, investigator decision or study termination by the sponsor.

As ASPEN-09-03 (MBC) is the only substudy open under ASPEN-09, the information reflected in the enrollment number, arms/interventions, outcome measures, and eligibility criteria currently includes only MBC.

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Recruiting
        • University Health Network, Princess Margaret Cancer Centre
  • France
      • Paris, France, 75005
        • Recruiting
        • Hopital de l'Institut Curie
      • Paris, France, 75015
        • Recruiting
        • Hopital Europeen Georges Pompidou (HEGP)
      • Poitiers, France, 86000
        • Recruiting
        • Centre Hospitalier Universitaire (CHU) de Poitiers
      • Rennes, France, 35042
        • Recruiting
        • Centre Eugene Marquis
  • Italy
      • Novara, Italy, 28100
        • Recruiting
        • Azienda Ospedaliero- Universitaria Maggiore della CaritÃ, SCDU Oncologia
    • AN
      • Torrette, AN, Italy, 60126
        • Recruiting
        • Azienda Ospedaliero Universitaria delle Marche
    • GE
      • Genova, GE, Italy, 16132
        • Recruiting
        • IRCCS Azienda Ospedaliera Metropolitana
  • Singapore
      • Singapore, Singapore, 168583
        • Recruiting
        • National Cancer Centre Singapore
      • Singapore, Singapore, 217562
        • Recruiting
        • Curie Oncology - Farrer
  • South Korea
      • Incheon, South Korea, 22332
        • Recruiting
        • Inha University Hospital
      • Seoul, South Korea, 05505
        • Recruiting
        • Asan Medical Center
      • Seoul, South Korea, 03080
        • Recruiting
        • Seoul National University Hospital
      • Seoul, South Korea, 03722
        • Recruiting
        • Severance Hospital, Yonsei University Health System
      • Seoul, South Korea, 06351
        • Recruiting
        • Samsung Medical Center
      • Seoul, South Korea, 08308
        • Recruiting
        • Korea University Guro Hospital
  • Spain
      • Barcelona, Spain, 08041
        • Recruiting
        • Hospital De La Santa Creu I Sant Pau
      • Madrid, Spain, 28007
        • Recruiting
        • Hospital Beata Maria Ana
    • Andalusia
      • Málaga, Andalusia, Spain, 29010
        • Recruiting
        • Hospital Universitario Virgen de la Victoria
      • Seville, Andalusia, Spain, 41009
        • Recruiting
        • Hospital Universitario Virgen Macarena
    • Catalonia
      • Lleida, Catalonia, Spain, 25198
        • Recruiting
        • Hospital Universitari Arnau de Villanova
  • United Kingdom
    • Greater London
      • London, Greater London, United Kingdom, EC1A 7BE
        • Recruiting
        • Barts Health NHS Trust - St Bartholomew's Hospital
    • Wales
      • Cardiff, Wales, United Kingdom, CF14 2TL
        • Recruiting
        • Velindre Cancer Centre, Velindre University NHS Trust
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85719
        • Recruiting
        • The University of Arizona Cancer Center - North Campus
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope
      • La Jolla, California, United States, 92037
        • Recruiting
        • UC San Diego Moores Cancer Center
      • Orange, California, United States, 928686
        • Recruiting
        • UC Irvine Health - Chao Family Comprehensive Cancer Center
    • Colorado
      • Denver, Colorado, United States, 80218
        • Recruiting
        • Saint Joseph Hospital - Cancer Centers of Colorado
      • Golden, Colorado, United States, 80401
        • Recruiting
        • Lutheran Hospital - Cancer Centers of Colorado
      • Grand Junction, Colorado, United States, 81501
        • Recruiting
        • Saint Mary's Regional Hospital - Cancer Centers of Colorado
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20037
        • Recruiting
        • The George Washington Medical facility Associates
    • Florida
      • Miami, Florida, United States, 33136
        • Recruiting
        • Sylvester Comprehensive Cancer Center
    • Illinois
      • Zion, Illinois, United States, 60099
        • Recruiting
        • City of Hope Chicago
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan Rogel Cancer Center
    • Minnesota
      • Saint Louis Park, Minnesota, United States, 55426
        • Recruiting
        • HealthPartners Frauenshuh Cancer Center
        • Contact:
          • Study Coordinator
    • Montana
      • Billings, Montana, United States, 59102
        • Recruiting
        • St. Vincent Regional Hospital - Cancer Centers of Montana
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Recruiting
        • Oncology Hematology West, PC dba Nebraska Cancer Specialists
        • Contact:
          • Study Coordinator
          • Phone Number: 402-334-4773
    • New York
      • New York, New York, United States, 10022
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
    • Ohio
      • Canton, Ohio, United States, 44718
        • Recruiting
        • Gabrail Cancer Center
        • Contact:
          • Study Coordinator
    • Texas
      • Dallas, Texas, United States, 75390
        • Recruiting
        • University of Texas Southwestern Medical Center
      • Houston, Texas, United States, 77030
        • Recruiting
        • Houston Methodist Cancer Center
      • Houston, Texas, United States, 77030
        • Recruiting
        • The University of Texas M.D. Anderson Cancer Center
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Virginia Cancer Specialists
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutchinson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Evorpacept+Trastuzumab+Chemo in participants with metastatic HER2+ breast cancer
  • Evorpacept (IV) - once every 3 weeks (Q3W)
  • Trastuzumab (IV) - once every 3 weeks (Q3W)

  • Chemotherapy (physician selects one of the following):

    • Capecitabine (Oral) twice a day for 14 days every 3 weeks
    • Eribulin (IV) twice every 3 weeks
    • Gemcitabine (IV) twice every 3 weeks
    • Paclitaxel (IV) once every 3 weeks (Q3W) or once weekly (QW)
    • Vinolrebine (IV) twice every 3 weeks
Drug: Paclitaxel
IV infusion
Other Names:
  • Taxol
Drug: Gemcitabine
IV infusion
Other Names:
  • Gemzar
Drug: Vinorelbine
IV infusion
Other Names:
  • Navelbine
Drug: Eribulin
IV infusion
Other Names:
  • Halaven
Drug: Evorpacept (ALX148)
IV infusion
Drug: Trastuzumab
IV infusion
Other Names:
  • Herceptin
Drug: Capecitabine
Oral administration
Other Names:
  • Xeloda

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR) using RECIST v1.1 based on BICR assessment
Time Frame: Approximately 6 months after the last participant is enrolled
Evaluate the ORR of evorpacept in combination with trastuzumab and single-agent chemotherapy in the sub-population of participants with metastatic HER2-positive breast cancer who express CD47 (CD47+). ORR is defined as a best overall response (BOR) of confirmed complete response (CR) or partial response (PR) using RECIST v1.1 based on BICR assessment.
Approximately 6 months after the last participant is enrolled

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR) based on Investigator assessment
Time Frame: Approximately 6 months after the last participant is enrolled
Evaluate the ORR of evorpacept in combination with trastuzumab and single-agent chemotherapy in the sub-population of participants with metastatic HER2-positive breast cancer who express CD47 (CD47+). ORR is defined as a best overall response (BOR) of confirmed complete response (CR) or partial response (PR) based on Investigator Assessment.
Approximately 6 months after the last participant is enrolled
Clinical Benefit Rate (CBR) using RECIST v1.1 based on BICR and Investigator assessment
Time Frame: Approximately 6 months after the last participant is enrolled
Evaluate the CBR of evorpacept in combination with trastuzumab and single-agent chemotherapy in the sub-population of participants with metastatic HER2-positive breast cancer who express CD47 (CD47+). CBR is defined as the proportion of participants whose BOR is confirmed PR, confirmed CR, or SD with duration >6 months using RECIST v1.1 based on BICR and Investigator assessment.
Approximately 6 months after the last participant is enrolled
Duration of Response (DoR) using RECIST v1.1 based on BICR and Investigator assessment
Time Frame: Approximately 6 months after the last participant is enrolled
Evaluate the DoR of evorpacept in combination with trastuzumab and single-agent chemotherapy in the sub-population of participants with metastatic HER2-positive breast cancer who express CD47 (CD47+). DoR is measured from the time measurement criteria are first met for CR / PR (whichever is first recorded) until documented progressive disease or death from any cause, whichever occurs first using RECIST v1.1 based on BICR and Investigator assessment.
Approximately 6 months after the last participant is enrolled
Progression-Free Survival (PFS) using RECIST v1.1 based on BICR and Investigator assessment
Time Frame: Approximately 6 months after the last participant is enrolled
Evaluate the PFS of evorpacept in combination with trastuzumab and single-agent chemotherapy in the sub-population of participants with metastatic HER2-positive breast cancer who express CD47 (CD47+). PFS is measured from the date of enrollment until documented progressive disease or death from any cause, whichever occurs first, using RECIST v1.1 based on BICR and Investigator assessment
Approximately 6 months after the last participant is enrolled
Overall Survival (OS)
Time Frame: Approximately 6 months after the last participant is enrolled
Evaluate the OS of evorpacept in combination with trastuzumab and single-agent chemotherapy in the sub-population of participants with metastatic HER2-positive breast cancer who express CD47 (CD47+). OS is defined as the time from the date of enrollment until death.
Approximately 6 months after the last participant is enrolled
Number of participants with adverse events (AEs) and with laboratory abnormalities
Time Frame: Enrollment to 28 days after the last administration of the study drug
AEs as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), timing, seriousness, and relationship to study drug. Laboratory abnormalities as characterized by type, frequency, severity, and timing.
Enrollment to 28 days after the last administration of the study drug
Maximum Concentration (Cmax)
Time Frame: Approximately 6 months after the last participant is enrolled
To evaluate the Cmax of evorpacept
Approximately 6 months after the last participant is enrolled
Time at Maximum Concentration (Tmax)
Time Frame: Approximately 6 months after the last participant is enrolled
To evaluate the Tmax of evorpacept
Approximately 6 months after the last participant is enrolled
Area under the Concentration-Time Curve (AUC)
Time Frame: Approximately 6 months after the last participant is enrolled
To evaluate the AUC of evorpacept
Approximately 6 months after the last participant is enrolled
Clearance (CL)
Time Frame: Approximately 6 months after the last participant is enrolled
To evaluate the CL of evorpacept
Approximately 6 months after the last participant is enrolled
Terminal elimination half-life (t1/2)
Time Frame: Approximately 6 months after the last participant is enrolled
To evaluate the t1/2 of evorpacept
Approximately 6 months after the last participant is enrolled
Evaluate the immunogenicity of evorpacept
Time Frame: Approximately 6 months after the last participant is enrolled
Measured by presence of human serum ADA (anti-evorpacept antibodies)
Approximately 6 months after the last participant is enrolled

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ALX Oncology Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 10, 2025

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2028

Study Registration Dates

First Submitted

May 22, 2025

First Submitted That Met QC Criteria

June 3, 2025

First Posted (Actual)

June 6, 2025

Study Record Updates

Last Update Posted (Actual)

June 5, 2026

Last Update Submitted That Met QC Criteria

June 4, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AT148009

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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