Trial results for the KEYNOTE-811 study (NCT03615326) investigating pembrolizumab (Keytruda) in combination with trastuzumab and chemotherapy for HER2-positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma were posted on ClinicalTrials.gov on 2025-03-17. The study showed that the pembrolizumab combination extended median overall survival to 20.0 months compared to 16.8 months for the control arm.
Background
The KEYNOTE-811 study aimed to evaluate the efficacy and safety of pembrolizumab plus trastuzumab in combination with standard of care (SOC) chemotherapy versus trastuzumab in combination with SOC chemotherapy in participants with HER2-positive gastric cancer or gastroesophageal junction (GEJ) adenocarcinoma.
Trial design
The KEYNOTE-811 study (NCT03615326) was a Phase 3, randomized trial that enrolled 738 participants. The study investigated pembrolizumab plus trastuzumab in combination with standard of care (SOC) chemotherapy versus trastuzumab in combination with SOC chemotherapy in participants with HER2-positive gastric cancer or gastroesophageal junction (GEJ) adenocarcinoma. The primary hypotheses of the study were that the pembrolizumab combination would be superior in terms of progression-free survival (PFS) per RECIST 1.1 as assessed by blinded independent central review (BICR) and overall survival (OS).
Key results
The trial results demonstrated improvements in key efficacy endpoints for the pembrolizumab combination arm compared to the standard of care arm.
- For Progression Free Survival (PFS) per RECIST 1.1 assessed by BICR:
- Median PFS for the Global Pembrolizumab + Standard of Care First Course group was 10.0 Months.
- Median PFS for the Global Standard of Care group was 8.1 Months.
A Log Rank analysis for PFS showed a Hazard Ratio (HR) of 0.73 (95.0% CI: 0.61 to 0.87) with a p-value of 0.0002.
- For Overall Survival (OS):
- Median OS for the Global Pembrolizumab + Standard of Care First Course group was 20.0 Months.
- Median OS for the Global Standard of Care First Course group was 16.8 Months.
A Log Rank analysis for OS showed a Hazard Ratio (HR) of 0.8 (95.0% CI: 0.67 to 0.94) with a p-value of 0.004.
- For Objective Response Rate (ORR) per RECIST 1.1 assessed by BICR:
- The Global Pembrolizumab + Standard of Care First Course group achieved an ORR of 72.6 Percentage of Participants.
- The Global Standard of Care First Course group achieved an ORR of 60.1 Percentage of Participants.
A Stratified Miettinen and Nurminen Method analysis for ORR showed a Difference in Percentage of 12.6 (95.0% CI: 5.6 to 19.4) with a p-value of 0.0002.
- For Duration of Response (DOR) per RECIST 1.1 assessed by BICR:
- Median DOR for the Global Pembrolizumab + Standard of Care First Course group was 11.13 Months.
- Median DOR for the Global Standard of Care First Course group was 9.5 Months.
- 348 Participants in the Global Pembrolizumab + Standard of Care First Course group experienced an adverse event.
- 346 Participants in the Global Standard of Care First Course group experienced an adverse event.
What this means
The results from the KEYNOTE-811 trial indicate that adding pembrolizumab to trastuzumab and chemotherapy significantly improved progression-free survival, overall survival, and objective response rates in patients with HER2-positive advanced gastric or gastroesophageal junction adenocarcinoma. The observed median OS extension of 3.2 months and PFS extension of 1.9 months, along with a higher objective response rate, suggest that this combination therapy could offer a meaningful clinical benefit for this patient population. The safety profile appears comparable between the two arms based on the number of participants experiencing adverse events.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03615326, titled "Pembrolizumab/Placebo Plus Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-811/KEYNOTE-811)," were posted on 2025-03-17 on clinicaltrials.gov.