Results from the PHASE2 study NCT05167409 investigating Pembrolizumab in combination with Evorpacept and Cetuximab for refractory microsatellite stable metastatic colorectal cancer were posted on 2026-07-22. The study, which was terminated, reported an Objective Response Rate (ORR) of 0 participants in two safety run-in cohorts and 1 participant in the expansion cohort.

Background

This study evaluated a combination therapy including Pembrolizumab, Evorpacept (ALX148), and Cetuximab for the treatment of refractory microsatellite stable metastatic colorectal cancer.

Trial design

The PHASE2 study, identified as NCT05167409, enrolled 19 participants with Microsatellite Stable Metastatic Colorectal Cancer. The study was designed to evaluate evorpacept (ALX148) in combination with cetuximab and pembrolizumab for this condition. The trial included a Stage 1 safety run-in evaluating Evorpacept at 10 mg/kg weekly and 15 mg/kg weekly, followed by a Stage 2 expansion cohort using the recommended dose.

Key results

Key efficacy and safety outcomes reported from the study included:

  • For Objective Response Rate (ORR):
    • In the Stage 1 safety run-in evaluating Evorpacept at 10 mg/kg Weekly, ORR was observed in 0 participants.
    • In the Stage 1 safety run-in evaluating Evorpacept at 15 mg/kg Weekly, ORR was observed in 0 participants.
    • In the Stage 2 expansion cohort, ORR was observed in 1 participant.
  • For Disease Control Rate (DCR):
    • In the Stage 1 safety run-in evaluating Evorpacept at 10 mg/kg Weekly, DCR was observed in 0 participants.
    • In the Stage 1 safety run-in evaluating Evorpacept at 15 mg/kg Weekly, DCR was observed in 1 participant.
    • In the Stage 2 expansion cohort, DCR was observed in 1 participant.
  • The Duration of Response (DOR) in the Stage 2 expansion cohort was 13.2 months.
  • For Progression-Free Survival (PFS):
    • The median PFS in the Stage 1 safety run-in evaluating Evorpacept at 10 mg/kg Weekly was 2.3 months.
    • The median PFS in the Stage 1 safety run-in evaluating Evorpacept at 15 mg/kg Weekly was 2.2 months.
  • Regarding the determination of the Recommended Dose (RD) of Evorpacept (ALX148) in combination with Cetuximab and Pembrolizumab:
    • In the Stage 1 safety run-in evaluating Evorpacept at 10 mg/kg Weekly, the RD was determined for 0 participants.
    • In the Stage 1 safety run-in evaluating Evorpacept at 15 mg/kg Weekly, the RD was determined for 1 participant.
    • In the Stage 2 expansion cohort, the RD was determined for 0 participants.

What this means

The termination of the PHASE2 study NCT05167409, coupled with the reported outcomes, suggests that the combination of Evorpacept, Cetuximab, and Pembrolizumab demonstrated limited efficacy in participants with refractory microsatellite stable metastatic colorectal cancer. The very low objective response rates and disease control rates across the different dose cohorts indicate that this particular regimen did not meet the expected clinical benefit in this challenging patient population.

Source

This information was sourced from ClinicalTrials.gov, documenting the results of trial NCT05167409, which were posted on 2026-07-22. The study details are available on clinicaltrials.gov.