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; Colorectal Cancer

Treatments: Drug: Capecitabine; Drug: Evorpacept (ALX148); Drug: Cetuximab; Drug: Trastuzumab; Drug: Paclitaxel; Drug: Vinorelbine; Drug: FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin); Drug: Eribulin; Drug: Gemcitabine

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) - randomized 1:1 to one of two arms (evorpacept + standard of care therapy vs. standard of care only)
• Metastatic colorectal cancer (CRC) - dose escalation phase to evaluate evorpacept in combination with other drugs
• Recurrent/metastatic head and neck cancer (HNSCC) - note that this substudy will not be open at the time of study initiation

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.

Enrollment: 280 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
• HER2 copy number amplified in ctDNA by sponsor's central laboratory
• 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).

CRC substudy:

• Histologically-confirmed left sided metastatic colorectal cancer, confirmed to be pMMR / MSS, KRAS / NRAS / BRAF WT, with tumor tissue available for molecular analysis.
• Progression on and after first line oxaliplatin-based standard of care (SOC) therapy for mCRC, with exclusion of an anti-epidermal growth factor receptor (EGFR) treatment.
• Adequate renal function - estimated creatinine clearance or glomerular filtration rate ≥60 mL/min as calculated using the Cockroft-Gault equation
• Adequate liver function:
• Aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase ≤2.5 x upper limit of normal (ULN) with the following exception:
• AST and ALT ≤2.5 x ULN; (≤5.0 x ULN if there is liver involvement secondary to tumor due to liver metastasis).
• Total bilirubin ≤1.5 x ULN.
• Most recent core or incisional biopsy sample prior to study entry, preferably taken after the most recent therapy, should be available for submission

Exclusion Criteria (all substudies):

• Participants with known CNS metastases unless treated and stable prior to enrollment
• Prior chemotherapy, radiation therapy or small molecule anti-cancer therapy within 14 days or 5 half-lives (whichever is shorter) of C1D1. 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
• Active known second malignancy within 3 years
• Other primary malignancy within 2 years
• Any condition that would be contraindicated to receiving trastuzumab

CRC substudy:

• Prior exposure to irinotecan-based therapy or has known toxicity to 5FU and / or irinotecan.
• Participants with known Gilberts disease.
• Has a diagnosis of known UGT1A1 deficiency.
• History of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease.
• Prior exposure to anti-EGFR therapies
• Diagnosis of immunodeficiency (with the exception of hypogammaglobulinemia) or is receiving chronic systemic steroid therapy or any other form of chronic immunosuppressive therapy within 7 days prior the first dose of study drug.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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280 participants in 3 patient groups

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

Experimental group

Description:

* Evorpacept (IV) - once every 3 weeks (Q3W) * Trastuzumab (IV) - Q3W * Chemotherapy (physician selects one of the following): * Capecitabine (Oral) 14 days every 3 weeks * Eribulin (IV) twice every 3 weeks * Gemcitabine twice every 3 weeks * Paclitaxel once every 3 weeks (Q3W) * Vinolrebine (IV) twice every 3 weeks

Treatment:

Drug: Gemcitabine

Drug: Eribulin

Drug: Vinorelbine

Drug: Paclitaxel

Drug: Trastuzumab

Drug: Evorpacept (ALX148)

Drug: Capecitabine

Trastuzumab+Chemo in participants with metastatic HER2+ breast cancer

Active Comparator group

Description:

Trastuzumab (IV) - Q3W * Chemotherapy (physician selects one of the following): * Capecitabine (Oral) 14 days every 3 weeks * Eribulin (IV) twice every 3 weeks * Gemcitabine twice every 3 weeks * Paclitaxel once every 3 weeks (Q3W) * Vinolrebine (IV) twice every 3 weeks

Treatment:

Drug: Gemcitabine

Drug: Eribulin

Drug: Vinorelbine

Drug: Paclitaxel

Drug: Trastuzumab

Drug: Capecitabine

Evorapacept + cetuximab + FOLFIRI in colorectal cancer participants

Experimental group

Description:

Regimen A * Evorpacept (IV) weekly (QW). Dose tbd based on cohort assigned * Cetuximab (IV) QW * FOLFIRI (IV) every 2 weeks (Q2W) * Regimen B * Evorpacept (IV) every 2 weeks (Q2W). Dose tbd based on cohort assigned * Cetuximab (IV) Q2W * FOLFIRI (IV) Q2W

Treatment:

Drug: FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)

Drug: Cetuximab

Drug: Evorpacept (ALX148)