ASPEN-09: A Study of Evorpacept in Combination With Anti-cancer Therapies in Advanced / Metastatic Malignancies

ALX Oncology

Status and phase: Enrolling; Phase 2; Phase 1

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 purpose of this study is to evaluate evorpacept with anti-cancer therapies in advanced/metastatic malignancies. The study is comprised of the following substudies:

• Metastatic HER2+ breast cancer (MBC) - single-arm substudy 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.
• Metastatic colorectal cancer (CRC) - dose escalation phase to evaluate evorpacept in combination with other drugs. This substudy is not recruiting.
• Recurrent/metastatic head and neck cancer (HNSCC) - dose escalation phase to evaluate evorpacept in combination with other drugs. This substudy is not recruiting.

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.

Not all substudies may be active and/or open to enrollment at a given time. Not all study centers may be participating in every substudy. MBC substudy will be the first to enroll - thus the information reflected in the enrollment number, arms/interventions, outcome measures, and eligibility criteria only include MBC at this time.

Enrollment: 80 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria (all substudies):

• Participants must have at least one measurable lesion as defined by RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) must be 0 to 1.
• Life expectancy of at least 3 months
• 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

MBC substudy:

• Histologically confirmed invasive HER2 positive breast cancer
• Available tumor tissue (FFPE slides or block). A fresh biopsy is preferred but optional.
• 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.
• 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)
• LVEF ≥50%
• Adequate renal function (estimated creatinine clearance ≥30 mL/min as calculated using the Cockroft-Gault 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).

Exclusion Criteria (all substudies):

• Participants with known CNS metastases unless treated and stable prior to enrollment

• Following anti-cancer therapy with insufficient washout before C1D1:

  1. chemotherapy, hormonal therapy, radiation therapy or small molecule anti-cancer therapy within 14 days or 5 half-lives (whichever is shorter) of C1D1.
  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 C1D1)

• Prior exposure to any anti-CD47 or anti-SIRPα agent.

• 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

MBC substudy:

• Has a diagnosis of complete dihydropyrimidine dehydrogenase (DPD) deficiency or significant toxicity with prior flurouracil (5FU) based regimen
• Other primary malignancy within 2 years
• Any condition that would be contraindicated to receiving trastuzumab

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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80 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) 14 days every 3 weeks * Eribulin (IV) twice every 3 weeks * Gemcitabine (IV) twice every 3 weeks * Paclitaxel (IV) once every 3 weeks (Q3W) * Vinolrebine (IV) twice every 3 weeks

Treatment:

Drug: Evorpacept (ALX148)

Drug: Gemcitabine

Drug: Vinorelbine

Drug: Trastuzumab

Drug: Eribulin

Drug: Paclitaxel

Drug: Capecitabine