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

NCT07007559 | Recruiting Phase 2 FDA Drug

• 1 other identifier: AT148009
• Study Type: interventional
• Target: 120
• Locations: 8 countries
• Sites: 44

Brief 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.

Conditions

Breast Cancer, Metastatic

Keywords

metastatic; Her2+; metastatic HER2-positive breast cancer; breast cancer; HER2-positive; Evorpacept; CD47; ERBB2; Enhertu; trastuzumab deruxtecan; ASPEN-09; Herceptin; solid tumors; trastuzumab; ALX148; mBC; ASPEN-Breast

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) using RECIST v1.1 based on BICR assessment

  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 Outcomes (12)

• Overall Response Rate (ORR) 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

  Approximately 6 months after the last participant is enrolled

• Duration of Response (DoR) 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

  Approximately 6 months after the last participant is enrolled

• Overall Survival (OS)

  Approximately 6 months after the last participant is enrolled

Study Arms (1)

Evorpacept+Trastuzumab+Chemo in participants with metastatic HER2+ breast cancer

EXPERIMENTAL

* 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: Evorpacept (ALX148); Drug: Trastuzumab; Drug: Paclitaxel; Drug: Capecitabine; Drug: Eribulin; Drug: Gemcitabine; Drug: Vinorelbine

Interventions

Evorpacept (ALX148) DRUG

IV infusion

Evorpacept+Trastuzumab+Chemo in participants with metastatic HER2+ breast cancer

Trastuzumab DRUG

IV infusion

Also known as: Herceptin

Evorpacept+Trastuzumab+Chemo in participants with metastatic HER2+ breast cancer

Paclitaxel DRUG

IV infusion

Also known as: Taxol

Evorpacept+Trastuzumab+Chemo in participants with metastatic HER2+ breast cancer

Capecitabine DRUG

Oral administration

Also known as: Xeloda

Evorpacept+Trastuzumab+Chemo in participants with metastatic HER2+ breast cancer

Eribulin DRUG

IV infusion

Also known as: Halaven

Evorpacept+Trastuzumab+Chemo in participants with metastatic HER2+ breast cancer

Gemcitabine DRUG

IV infusion

Also known as: Gemzar

Evorpacept+Trastuzumab+Chemo in participants with metastatic HER2+ breast cancer

Vinorelbine DRUG

IV infusion

Also known as: Navelbine

Evorpacept+Trastuzumab+Chemo in participants with metastatic HER2+ breast cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• 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.

Sponsors & Collaborators

• ALX Oncology Inc.: lead

Study Sites (44)

The University of Arizona Cancer Center - North Campus

Tucson, Arizona, 85719, United States

RECRUITING

City of Hope

Duarte, California, 91010, United States

RECRUITING

UC San Diego Moores Cancer Center

La Jolla, California, 92037, United States

RECRUITING

UC Irvine Health - Chao Family Comprehensive Cancer Center

Orange, California, 928686, United States

RECRUITING

Saint Joseph Hospital - Cancer Centers of Colorado

Denver, Colorado, 80218, United States

RECRUITING

Lutheran Hospital - Cancer Centers of Colorado

Golden, Colorado, 80401, United States

RECRUITING

Saint Mary's Regional Hospital - Cancer Centers of Colorado

Grand Junction, Colorado, 81501, United States

RECRUITING

The George Washington Medical facility Associates

Washington D.C., District of Columbia, 20037, United States

RECRUITING

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

RECRUITING

City of Hope Chicago

Zion, Illinois, 60099, United States

RECRUITING

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

RECRUITING

HealthPartners Frauenshuh Cancer Center

Saint Louis Park, Minnesota, 55426, United States

RECRUITING

St. Vincent Regional Hospital - Cancer Centers of Montana

Billings, Montana, 59102, United States

RECRUITING

Oncology Hematology West, Pc Dba Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10022, United States

RECRUITING

Gabrail Cancer Center

Canton, Ohio, 44718, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

Houston Methodist Cancer Center

Houston, Texas, 77030, United States

RECRUITING

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

University Health Network, Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

Hopital de l'Institut Curie

Paris, 75005, France

RECRUITING

Hopital Europeen Georges Pompidou (HEGP)

Paris, 75015, France

RECRUITING

Centre Hospitalier Universitaire (CHU) de Poitiers

Poitiers, 86000, France

RECRUITING

Centre Eugene Marquis

Rennes, 35042, France

RECRUITING

Azienda Ospedaliero Universitaria delle Marche

Torrette, AN, 60126, Italy

RECRUITING

IRCCS Azienda Ospedaliera Metropolitana

Genova, GE, 16132, Italy

RECRUITING

Azienda Ospedaliero- Universitaria Maggiore della CaritÃ, SCDU Oncologia

Novara, 28100, Italy

RECRUITING

National Cancer Centre Singapore

Singapore, 168583, Singapore

RECRUITING

Curie Oncology - Farrer

Singapore, 217562, Singapore

RECRUITING

Inha University Hospital

Incheon, 22332, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

Korea University Guro Hospital

Seoul, 08308, South Korea

RECRUITING

Hospital Universitario Virgen de la Victoria

Málaga, Andalusia, 29010, Spain

RECRUITING

Hospital Universitario Virgen Macarena

Seville, Andalusia, 41009, Spain

RECRUITING

Hospital Universitari Arnau de Villanova

Lleida, Catalonia, 25198, Spain

RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

RECRUITING

Hospital Beata Maria Ana

Madrid, 28007, Spain

RECRUITING

Barts Health NHS Trust - St Bartholomew's Hospital

London, Greater London, EC1A 7BE, United Kingdom

RECRUITING

Velindre Cancer Centre, Velindre University NHS Trust

Cardiff, Wales, CF14 2TL, United Kingdom

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

ALX148; Trastuzumab; Paclitaxel; Capecitabine; eribulin; Gemcitabine; Vinorelbine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Central Study Contacts

Cheng Quah, MD

CONTACT

650-466-7125; info@alxoncology.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2025
• First Posted: June 6, 2025
• Study Start: December 10, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: June 5, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (21); SG (2); KR (6); ES (5); GB (2); IT (3); FR (4); CA (1)