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

ALX Oncology

Status and phase

Enrolling

Phase 2

Conditions

Breast Cancer, Metastatic

Treatments

Drug: Capecitabine

Drug: Paclitaxel

Drug: Eribulin

Drug: Vinorelbine

Drug: Trastuzumab

Drug: Gemcitabine

Drug: Evorpacept (ALX148)

Study type

Interventional

Funder types

Industry

Identifiers

NCT07007559

AT148009

Details and patient eligibility

About

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.

Full 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.

Enrollment

120 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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 design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

120 participants in 1 patient group

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

Experimental group

Description:

* 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