Trial results for a study investigating pembrolizumab in combination therapies for HER2+ gastrointestinal cancers were posted on ClinicalTrials.gov on 2025-09-09. The study, NCT04430738, detailed safety outcomes including dose-limiting toxicities and treatment-emergent adverse events across various cohorts.
Background
The trial, titled 'Tucatinib Plus Trastuzumab and Oxaliplatin-based Chemotherapy or Pembrolizumab-containing Combinations for HER2+ Gastrointestinal Cancers,' aimed to evaluate the safety and efficacy of these combinations. It focused on participants with HER2-positive gastrointestinal cancers, including Colorectal Carcinoma, Gastric Adenocarcinoma, GEJ Adenocarcinoma, Esophageal Adenocarcinoma, and Cholangiocarcinoma.
Trial design
The study, NCT04430738, is a Phase 2 trial with an enrollment of 40 participants. It investigates combinations including tucatinib, trastuzumab, oxaliplatin, leucovorin, and fluorouracil, alongside pembrolizumab-containing combinations. The trial is designed to assess safety and efficacy in participants with HER2-positive gastrointestinal cancers, specifically Colorectal Carcinoma, Gastric Adenocarcinoma, GEJ Adenocarcinoma, Esophageal Adenocarcinoma, and Cholangiocarcinoma.
Key results
The trial results posted primarily detailed safety outcomes across different cohorts. For the outcome 'Number of Participants With Renal Dose-Limiting Toxicities (DLTs): Phase 1b (Cohort 1A and 1B)':
- Cohort 1A reported 0 Participants with renal DLTs.
- Cohort 1B reported 1 Participant with renal DLTs.
For 'Number of Participants With Treatment Emergent Adverse Events (TEAEs): Phase 1b (Cohort 1E and 1F)':
- Cohort 1E reported 4 Participants with TEAEs.
- Cohort 1F reported 8 Participants with TEAEs.
Regarding 'Number of Participants With Treatment Related TEAEs: Phase 1b (Cohort 1E and 1F)':
- Cohort 1E reported 4 Participants with treatment-related TEAEs.
- Cohort 1F reported 8 Participants with treatment-related TEAEs.
For 'Number of Participants With Greater Than or Equal to (>=) Grade 3 TEAEs: Phase 1b (Cohort 1E and 1F)':
- Cohort 1E reported 4 Participants with >= Grade 3 TEAEs.
- Cohort 1F reported 7 Participants with >= Grade 3 TEAEs.
For 'Number of Participants With >= Grade 3 Treatment Related TEAEs: Phase 1b (Cohort 1E and 1F)':
- Cohort 1E reported 4 Participants with >= Grade 3 treatment-related TEAEs.
- Cohort 1F reported 7 Participants with >= Grade 3 treatment-related TEAEs.
Finally, for 'Number of Participants With Any Serious Adverse Event (SAE): Phase 1b (Cohort 1E and 1F)':
- Cohort 1E reported 1 Participant with any SAE.
- Cohort 1F reported 6 Participants with any SAE.
What this means
The posted results provide initial safety data for pembrolizumab-containing combinations and other anti-cancer drugs in HER2-positive gastrointestinal cancers. The varying numbers of dose-limiting toxicities, treatment-emergent adverse events, and serious adverse events across the different cohorts offer insights into the safety profile of these complex regimens. These findings are crucial for understanding the tolerability of these combinations as the Phase 2 trial progresses.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04430738, titled 'Tucatinib Plus Trastuzumab and Oxaliplatin-based Chemotherapy or Pembrolizumab-containing Combinations for HER2+ Gastrointestinal Cancers,' were posted on 2025-09-09 on clinicaltrials.gov.