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

Plain English Summary

ASPEN-09-03: A Study of Evorpacept in Combination With Trastuzumab and Chemotherapy in Metastatic HER2-Positive Breast Cancer is a Phase 2 clinical trial sponsored by ALX Oncology Inc. studying Breast Cancer, Metastatic. This trial tests a new drug, evorpacept, combined with standard treatments (trastuzumab and chemotherapy) for advanced HER2-positive breast cancer. It is for patients with HER2-positive breast cancer that has spread and has not responded to a previous treatment called trastuzumab-deruxtecan. Participation involves receiving evorpacept along with trastuzumab and one of several chemotherapy options, given through IV infusions or pills. Alternative treatments include other chemotherapy regimens, targeted therapies, or hormone therapy, depending on the patient's specific situation. The trial aims to enroll 120 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients with confirmed HER2-positive invasive breast cancer that has spread to other parts of the body can join. You must have previously received at least one line of therapy including trastuzumab-deruxtecan for your advanced cancer. Participants must be between 18 and 75 years old, with good general health and organ function (heart, kidney, liver). Patients with brain metastases that are not stable, or those who have had certain prior cancer therapies or autoimmune conditions, may not be eligible. This trial is studying Breast Cancer, Metastatic, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures how many patients' tumors shrink or disappear (Overall Response Rate), indicating how well the combination treatment works to control the cancer. The specific primary outcome measures are: Overall Response Rate (ORR) using RECIST v1.1 based on BICR assessment (Approximately 6 months after the last participant is enrolled). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a need for new treatment options for patients with HER2-positive metastatic breast cancer who have progressed after receiving trastuzumab-deruxtecan, a common and effective therap Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Breast Cancer, Metastatic, where improved treatment options are needed.

Investor Insight

This trial signals ALX Oncology's focus on expanding the use of evorpacept in a significant market segment, with potential for improved outcomes in HER2-positive breast cancer. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if this trial is a good fit for you, considering your specific cancer and treatment history. Participation involves regular clinic visits for drug infusions, blood tests, scans to monitor your cancer, and to check for side effects. Be prepared for potential side effects from the study drugs and discuss any concerns with your healthcare team promptly. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 120 participants

Interventions

• DRUG: Evorpacept (ALX148) — IV infusion
• DRUG: Trastuzumab — IV infusion
• DRUG: Paclitaxel — IV infusion
• DRUG: Capecitabine — Oral administration
• DRUG: Eribulin — IV infusion

Primary Outcomes

• Overall Response Rate (ORR) using RECIST v1.1 based on BICR assessment (Approximately 6 months after the last participant is enrolled)

Secondary Outcomes

• 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)

Full Eligibility 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.

Trial Locations

• The University of Arizona Cancer Center - North Campus, Tucson, Arizona, United States
• City of Hope, Duarte, California, United States
• Saint Joseph Hospital - Cancer Centers of Colorado, Denver, Colorado, United States
• Lutheran Hospital - Cancer Centers of Colorado, Golden, Colorado, United States
• Saint Mary's Regional Hospital - Cancer Centers of Colorado, Grand Junction, Colorado, United States
• The George Washington Medical facility Associates, Washington D.C., District of Columbia, United States
• City of Hope Chicago, Zion, Illinois, United States
• University of Michigan Rogel Cancer Center, Ann Arbor, Michigan, United States
• HealthPartners Frauenshuh Cancer Center, Saint Louis Park, Minnesota, United States
• St. Vincent Regional Hospital - Cancer Centers of Montana, Billings, Montana, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Breast Cancer
• Metastatic Breast Cancer
• HER2-Positive Breast Cancer
• Advanced Breast Cancer
• Trastuzumab-resistant Breast Cancer
• Oncology
• Medical Oncology
• Chemotherapy
• Targeted Therapy
• Immunotherapy

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