Study of Evorpacept (ALX148) With Cetuximab and Pembrolizumab for Refractory Microsatellite Stable Metastatic Colorectal Cancer

NCT05167409 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: 22-0110.ccNCI-2022-02019AGICC-ALX148 21CRC01
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 4

Brief Summary

This Phase 2 clinical study will evaluate evorpacept (ALX148) in combination with cetuximab and pembrolizumab for refractory microsatellite stable metastatic colorectal cancer

Conditions

Microsatellite Stable Metastatic Colorectal Cancer

Keywords

evorpacept (ALX148); Cetuximab; Pembrolizumab; CRC; colorectal cancer; microsatellite stable; MSS; CD47; SIRPa

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR)

  A patient is considered to be an objective responder if their best overall response (BOR) of their follow-up tumor assessments was assessed to be complete response (CR) or partial response (PR) per RECIST v1.1. ORR is defined as the proportion of patients who were classified as objective responders.

  The duration of time during which tumor assessments were performed for each individual patient. Per protocol, assessments will continue until disease progression. The latest assessment was performed at Cycle 21, Day 15 (14.5 mo after informed consent)

• Determine the Recommended Dose (RD) of Evorpacept (ALX148) in Combination With Cetuximab and Pembrolizumab

  The recommended dose (RD) of evorpacept was determined by evaluating the totality of the first-cycle clinical data. Rules to determine the RD based on the number of patients experiencing a dose-limiting toxicity (DLT) were defined in the protocol.

  During the safety run-in, each patient must have completed at least the 1st cycle (3 weeks) of treatment.

Secondary Outcomes (4)

• Disease Control Rate (DCR)

  The duration of time during which tumor assessments were performed for each individual patient. Per protocol, assessments will continue until disease progression. The latest assessment was performed at Cycle 21, Day 15.

• Duration Of Response (DOR)

  From date of 1st response (CR or PR) until either progression (PD or death) or censoring date

• Progression-Free Survival (PFS)

  For each subject, from enrollment until the end of their months-to-progression (as defined above)

• Overall Survival (OS)

  For each subject, from enrollment until the end of their months-to-death time (as defined above)

Other Outcomes (4)

• ORR - Response-Evaluable Population

  The duration of time during which tumor assessments were performed for each patient, until they experience disease progression. The latest timepoint an assessment was performed was at Cycle 21 Day 15.

• DCR - Response-Evaluable Population

  The duration of time during which tumor assessments were performed for each individual patient. Per protocol, assessments will continue until disease progression. The latest assessment was performed at Cycle 21, Day 15.

• PFS - Response-Evaluable Population

  For each subject, from enrollment until the end of their months-to-progression (as defined above)

Study Arms (3)

Stage 1: Safety run-in evaluating evorpacept at 15 mg/kg weekly

EXPERIMENTAL

Doses: * Evorpacept (ALX148) dose level (DL) 1: 15 mg/kg weekly * Cetuximab: 400 mg/m2, then 250 mg/m2 weekly * Pembrolizumab: 200 mg every 3 weeks

Drug: Evorpacept (ALX148); Drug: Cetuximab; Drug: Pembrolizumab

Stage 1: Safety run-in evaluating evorpacept at 10 mg/kg weekly

EXPERIMENTAL

Doses: * Evorpacept (ALX148) dose level (DL) -1: 10 mg/kg weekly * Cetuximab: 400 mg/m2, then 250 mg/m2 weekly * Pembrolizumab: 200 mg every 3 weeks

Drug: Evorpacept (ALX148); Drug: Cetuximab; Drug: Pembrolizumab

Stage 2: Expansion cohort using recommended dose (RD) of evorpacept

EXPERIMENTAL

Doses: * Evorpacept (ALX148) dose level (DL) 1: 15 mg/kg weekly * Cetuximab: 400 mg/m2, then 250 mg/m2 weekly * Pembrolizumab: 200 mg every 3 weeks

Drug: Evorpacept (ALX148); Drug: Cetuximab; Drug: Pembrolizumab

Interventions

Evorpacept (ALX148) DRUG

IV QW

Also known as: evorpacept

Stage 1: Safety run-in evaluating evorpacept at 10 mg/kg weekly; Stage 1: Safety run-in evaluating evorpacept at 15 mg/kg weekly; Stage 2: Expansion cohort using recommended dose (RD) of evorpacept

Cetuximab DRUG

IV QW

Also known as: Erbitux

Stage 1: Safety run-in evaluating evorpacept at 10 mg/kg weekly; Stage 1: Safety run-in evaluating evorpacept at 15 mg/kg weekly; Stage 2: Expansion cohort using recommended dose (RD) of evorpacept

Pembrolizumab DRUG

IV Q3W

Also known as: Keytruda

Stage 1: Safety run-in evaluating evorpacept at 10 mg/kg weekly; Stage 1: Safety run-in evaluating evorpacept at 15 mg/kg weekly; Stage 2: Expansion cohort using recommended dose (RD) of evorpacept

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible to participate in this study, an individual must meet all of the following criteria at screening (any assessments included in the Schedule of Events \[Section 1.3\] on Cycle 1 Day 1 must also continue to be met for the patient to remain eligible):
• Provision to sign and date the consent form.
• Able to comply with all study procedures and be available for the duration of the study in the Investigator's judgment.
• Age ≥ 18 years on the day of signing informed consent
• If in Cohort A, the patient must state willingness to undergo pre- and post-treatment biopsies. According to the Investigator's judgement, the planned biopsies should not expose the patient to substantially increased risk of complications.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically confirmed unresectable metastatic colorectal adenocarcinoma.
• All primary tumor locations are allowed
• Measurement of EGFR expression by immunohistochemistry is not required
• Progression on at least two prior lines of therapy for unresectable metastatic colorectal adenocarcinoma.
• A patient who progressed on a single line of therapy including a fluoropyrimidine, oxaliplatin, and irinotecan for unresectable metastatic colorectal adenocarcinoma (e.g., FOLFIRINOX or FOLFOXIRI) is eligible.
• Microsatellite stable or proficient mismatch repair status documented (only one of these criteria is needed, however if one criterion is met and one is not met then the patient is excluded)
• Measurable disease, according to RECIST v1.1. Previously irradiated lesions are not considered measurable unless progression has been documented in the lesion. Note that lesions intended to be biopsied should not be target lesions.
• Adequate hematologic and end organ function, defined by the following laboratory results:
• ANC ≥ 1.5 × 109/L

You may not qualify if:

• Patients with known MSI-high status or known mismatch repair deficiency (dMMR)
• Patients in whom both mismatch repair and microsatellite stability status are unknown
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to Cycle 1 Day 1.
• Systemic anti-cancer therapy within 4 weeks of starting study treatment (6 weeks for mitomycin C or nitrosureas). If systemic anti-cancer therapy was given within 4 weeks, patient may be included if 5 times the elimination half-life of the drug has passed.
• Malignancies other than CRC within 3 years prior to Cycle 1 Day 1 with the exception of those with a negligible risk of metastasis or death (e.g., expected 5-year overall survival \> 90%) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, and ductal carcinoma in situ treated surgically with curative intent).
• Prior radiation therapy within 14 days prior to study Cycle 1 Day 1 and/or persistence of radiation-related adverse effects. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease. However, palliative radiation therapy (as long as it does not involve target lesions) is permitted on the study.
• Prior allogeneic bone marrow transplantation or solid organ transplant for another malignancy in the past.
• Spinal cord compression not definitively treated with surgery and/or radiation.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
• Uncontrolled tumor related pain. Patients who require narcotic pain medication during screening should be on a stable dose regimen for seven days prior to Cycle 1 Day 1.
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to any of the study medications or their classes
• History of red meat allergy or history of tick bite (these may increase the risk of a cetuximab infusion reaction).
• Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• Prior treatment with any anti-CD47 or anti-SIRPα drugs
• Left-sided (at or distal to the splenic flexure) RAS/BRAF WT mCRC who are EGFR inhibitor naïve.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• ALX Oncology Inc.: collaborator
• Merck Sharp & Dohme LLC: collaborator
• Eli Lilly and Company: collaborator
• Criterium, Inc.: collaborator
• Academic GI Cancer Consortium (AGICC): collaborator

Study Sites (4)

University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Rutgers Cancer insititute

New Brunswick, New Jersey, 08903, United States

Location

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

Location

Related Publications (1)

• Lentz RW, Lang J, Pitts TM, Blatchford P, Hu J, Jordan KR, Van Bokhoven A, Bagby SM, Dominguez ATA, Binns CA, Robinson HR, Balmaceda N, Baiyee E, Leal AD, Kim SS, Davis SL, Lieu CH, Wadlow RC, Spencer K, Scott AJ, Boland PM, Hochster HS, Messersmith WA. Phase II Clinical Trial and Preclinical Evaluation of a Novel CD47 Blockade Combination in Refractory Microsatellite-Stable Metastatic Colorectal Cancer. Cancer Res Commun. 2025 Nov 1;5(11):2039-2052. doi: 10.1158/2767-9764.CRC-25-0332.

  PMID: 41171165 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

ALX148; Cetuximab; pembrolizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

These results must be interpreted with caution in the context of limited sample size due to early termination of study enrollment.

Results Point of Contact

• Title: Wells Messersmith, MD
• Organization: University of Colorado

WELLS.MESSERSMITH@CUANSCHUTZ.EDU

303-724-0747

Study Officials

• Wells Messersmith, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2021
• First Posted: December 22, 2021
• Study Start: July 28, 2022
• Primary Completion: October 30, 2024
• Study Completion: October 30, 2024
• Last Updated: July 22, 2026
• Results First Posted: July 22, 2026

Record last verified: 2026-06

Locations

US (4)