Evorpacept added to standard therapy shows encouraging response rates in HER2-positive gastric cancer
Primary endpointInvestigator-assessed objective response rate (ORR)
In ITT population
Where these numbers come from
“The investigator-assessed ORRs were 40.3% (evo + TRP) versus 26.6% (TRP) in the ITT population and 54.8% versus 23.1% in the fresh biopsy HER2+ subgroup.”
The publication
In a phase 2 trial of 127 patients with advanced HER2-positive gastric or gastroesophageal junction cancer, adding evorpacept to trastuzumab, ramucirumab, and paclitaxel resulted in an investigator-assessed objective response rate of 40.3% compared with 26.6% for the standard triple therapy alone. This 13.7 percentage point difference exceeded the prespecified threshold for benefit, although response rates did not meet the prespecified statistical criterion against the 30% historical benchmark.
Who the findings apply to
The trial enrolled patients with pretreated, human epidermal growth factor receptor 2 (HER2)-overexpressing, advanced gastric or gastroesophageal junction cancer.
Participants were randomized to receive either evorpacept plus trastuzumab, ramucirumab, and paclitaxel or the standard triple therapy alone.
A subgroup analysis focused on patients with HER2 overexpression confirmed by a post-trastuzumab fresh tumor biopsy.
Why this matters
The study addresses the need for more effective treatment options for patients with advanced gastric or gastroesophageal junction cancer that has progressed after prior therapy. By blocking the CD47-signal regulatory protein alpha interaction, evorpacept enhances antibody-dependent cellular phagocytosis, potentially improving the efficacy of the existing trastuzumab, ramucirumab, and paclitaxel regimen. The observed increase in response rates suggests that this combination may offer a meaningful clinical advantage for this specific patient group, although the results did not meet the prespecified statistical criterion for superiority over the historical 30% benchmark in the overall population.
What the study found
In the intent-to-treat population, the investigator-assessed objective response rate was 40.3% for the evorpacept combination versus 26.6% for the control group, a difference of 13.7 percentage points.
In the fresh biopsy HER2-positive subgroup, the objective response rate was 54.8% for the evorpacept combination versus 23.1% for the control group, a difference of 31.7 percentage points.
These differences exceeded the prespecified thresholds for improvement in both the overall population and the fresh biopsy subgroup, meeting one of the two primary objectives of the trial.
What the result does not establish
The objective response rates in both the overall population and the fresh biopsy subgroup did not meet the prespecified statistical criterion for superiority over the historical 30% benchmark, with one-sided P-values of 0.0949 and 0.030, respectively.
Hematologic toxicities were more common in the group receiving evorpacept, although overall safety profiles were similar between the two arms.
The study was a phase 2 trial, and the results are based on investigator-assessed endpoints, with blinded independent central review serving as a key secondary endpoint.
Authors’ conclusion
“In summary, evo + TRP showed encouraging efficacy with manageable safety in advanced gastric/gastroesophageal junction cancer. ClinicalTrials.gov identifier: NCT05002127 .”
Study and sources
Evorpacept plus trastuzumab, ramucirumab and paclitaxel in HER2-positive gastric cancer: a randomized phase 2 trial
Randomised trial · Phase 2 · Nature medicine · 2026-09-24
Sources and limitations
- PubMed record PMID 42786305 (PubMed / NLM · 2026-09-26)
- Trial registry NCT05002127 (ClinicalTrials.gov · 2026-09-26)
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