Clinical trial NCT07007559: ASPEN-09: A Study of Evorpacept in Combination With Anti-cancer Therapies in Advanced / Metastatic Malignancies
Official title: ASPEN-09: A Phase 1b/2, Multicenter, Multi Arm Study of Evorpacept in Combination With Anti-cancer Therapies in Advanced / Metastatic Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Breast Cancer, Metastatic
Colorectal Cancer
Keywords: metastatic
colorectal
Her2+
metastatic HER2-positive breast cancer
breast cancer
HER2-positive
Evorpacept
CRC
CD47
ERBB2
Enhertu
trastuzumab deruxtecan
ASPEN-09
Herceptin
solid tumors
trastuzumab
Erbitux
cetuximab
ALX148
Lead sponsor: ALX Oncology Inc.
Sponsor class: INDUSTRY
First posted: 2025-06-06
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This is a basket study with substudies based on indications.
Primary purpose: TREATMENT

Brief summary: 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

Detailed 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.

Eligibility 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.

Primary outcomes:
measure: MBC substudy: Overall Response Rate
timeFrame: Approximately 6 months after the last participant is randomized
measure: CRC substudy: Determine the safety and tolerability of evorpacept in combination with cetuximab and FOLFIRI
timeFrame: 28 days from the first dose of evorpacept
measure: CRC substudy: Determine the MAD/MTD, the RP2D and recommended regimen
timeFrame: 28 days from first dose of evorpacept
Secondary outcomes:
measure: MBC substudy: Assess secondary measures of efficacy
timeFrame: Approximately 6 months after the last participant is randomized
measure: MBC substudy: Evaluate the safety profile of evorpacept in combination with trastuzumab and each of the chemotherapy regimens
timeFrame: Enrollment to 28 days after the last administration of the study drug
measure: All substudies: Characterize single and multiple dose PK of evorpacept
timeFrame: Approximately 6 months after the last participant is randomized
measure: All substudies: Evaluate the immunogenicity of evorpacept
timeFrame: Approximately 6 months after the last participant is randomized
measure: CRC substudy: Evaluate the overall safety profile of evorpacept in combination with other agents
timeFrame: Enrollment to 28 days after the last administration of the study drug
measure: CRC substudy: Evaluate the anti-tumor activity of evorpacept
timeFrame: Approximately 6 months after the last participant is randomized
Other outcomes:
Locations:
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
Study officials:
References: