A Study of Evorpacept (ALX148) in Patients with Metastatic HER2-Positive Breast Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alx Oncology Holdings Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

13 Mar 2026 → ongoing

Decision date (initial)

2026-01-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ALX Oncology Inc.

External identifiers

EU CT number

2025-522012-16-00

ClinicalTrials.gov

NCT07007559

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Pharmacokinetic, Safety, Therapy, Efficacy

To evaluate the overall response rate of evorpacept in combination with trastuzumab and single-agent chemotherapy in the sub-population of participants with metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) who have HER2 copy number amplification in ctDNA at baseline (ctDNA+).

Secondary objectives 4

1. • To assess secondary measures of efficacy for evorpacept administered in combination with trastuzumab and chemotherapy in the sub-population of participants with metastatic HER2-positive ctDNA+ BC.
2. • To evaluate the safety profile of evorpacept in combination with trastuzumab and each of the chemotherapy agents.
3. • To characterize pharmacokinetics (PK) of evorpacept in combination with trastuzumab and chemotherapy.
4. • To evaluate the immunogenicity of evorpacept.

Conditions and MedDRA coding

Breast Cancer

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Master Protocol • Participants must have at least one measurable lesion as defined by RECIST v1.1.
2. Substudy Protocol: • Eligible to receive one of the following chemotherapy options (capecitabine, eribulin, gemcitabine, paclitaxel or vinorelbine)
3. Substudy Protocol: • Adequate renal function (estimated creatinine clearance ≥30 mL/min as calculated using the Cockroft-Gault equation
4. Substudy Protocol: • 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).
5. Master Protocol • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) must be 0 to 1.
6. Master Protocol • Life expectancy of at least 3 months
7. Master Protocol • 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 which do not constitute a safety risk by Investigator judgment
8. Substudy Protocol: • Histologically confirmed invasive HER2 positive breast cancer
9. Substudy Protocol: • Received at least one prior line of therapy including T-DXd for locally advanced/metastatic HER2 positive 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.
10. Substudy Protocol: • Progressed on or following the most recent line of therapy
11. Substudy Protocol: • LVEF ≥50%

Exclusion criteria 11

1. Master Protocol: • Participants with known CNS metastases unless treated and stable prior to enrollment
2. Substudy Protocol: • Has a diagnosis of complete dihydropyrimidine dehydrogenase (DPD) deficiency or significant toxicity with prior flurouracil (5FU) based regimen
3. Substudy Protocol: • Other primary malignancy within 2 years
4. Substudy Protocol: • Any condition that would be contraindicated to receiving trastuzumab
5. Master Protocol: • Following anti-cancer therapy with insufficient washout : 1. chemotherapy, hormonal therapy, radiation therapy or small molecule anti-cancer therapy within 14 days 2. Immune therapy or other biologic therapy (e.g., monoclonal antibodies, antibody-drug conjugates) for the treatment of cancer for: 28 days
6. Master Protocol: • Prior exposure to any anti-CD47 or anti-SIRPα agent.
7. Master Protocol: • History of autoimmune hemolytic anemia, autoimmune thrombocytopenia, or hemolytic transfusion reaction.
8. Master Protocol: • Had an allogeneic tissue/solid organ transplant.
9. Master Protocol: • Any active, unstable cardiovascular disease
10. Master Protocol: • 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).
11. Master Protocol: • Has an active autoimmune disease that has required systemic treatment in past 2 years

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall response rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) based on Blinded Independent Central Review (BICR) assessment.

Secondary endpoints 6

1. • ORR based on Investigator assessment.
2. • Clinical Benefit Rate (CBR), Duration of Response (DoR), and Progression Free Survival (PFS), using RECIST v1.1 based on BICR and Investigator assessment, and Overall Survival (OS).
3. • Adverse Events (AEs) as characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 [NCI CTCAE v5.0]), timing, seriousness, and relationship to study drug.
4. • Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0) and timing.
5. • PK parameters of evorpacept such as maximum concentration (Cmax), time at maximum concentration (Tmax), area under the concentration-time curve (AUC), clearance (CL), and terminal elimination half-life (t1/2) as data permit.
6. • Presence of human serum anti-drug antibodies (ADAs) (anti-evorpacept antibodies).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 10

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alx Oncology Holdings Inc.

Sponsor organisation

Alx Oncology Holdings Inc.

Address

323 Allerton Avenue

City

South San Francisco

Postcode

94080-4816

Country

United States

Scientific contact point

Organisation

Alx Oncology Holdings Inc.

Contact name

ALX Oncology Inc.

Public contact point

Organisation

Alx Oncology Holdings Inc.

Contact name

ALX Oncology Inc.

Third parties 7

Locations

3 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 31 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications