Trial results for a Phase 1 study evaluating pembrolizumab in combination with XL888 for patients with advanced gastrointestinal cancer were posted on ClinicalTrials.gov on 2026-05-22. The study, which enrolled 47 participants, focused on determining the recommended Phase 2 dose of the combination therapy.
Background
The study investigated the combination of pembrolizumab (Keytruda) and XL888 in patients with advanced gastrointestinal cancer, including colorectal adenocarcinoma, metastatic pancreatic adenocarcinoma, recurrent colorectal carcinoma, recurrent pancreatic carcinoma, and stage III colorectal cancer. XL888 is an Hsp90 inhibitor, which may stop the growth of tumor cells by blocking enzymes needed for cell growth. Pembrolizumab is a monoclonal antibody that may block tumor growth by targeting certain cells. The trial aimed to explore if giving XL888 with pembrolizumab could be an effective treatment approach for these cancers.
Trial design
The completed Phase 1 study (NCT03095781) enrolled a total of 47 participants with advanced gastrointestinal cancer, specifically including colorectal adenocarcinoma, metastatic pancreatic adenocarcinoma, recurrent colorectal carcinoma, recurrent pancreatic carcinoma, and stage III colorectal cancer. The primary objective of this study was to determine the side effects and best dose of XL888 when given together with pembrolizumab.
Key results
The trial assessed the recommended Phase 2 dose of the combination of XL888 and pembrolizumab, as evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0. The participant counts reported for various dose groups and arms are as follows:
- For Dose Expansion Pancreatic Cancer (Arm A), participant counts of 14, 10, and 3 were reported.
- For Dose Expansion Colorectal Cancer (Arm B), participant counts of 16, 6, and 3 were reported.
- For the Dose Escalation 45 mg PO Twice Weekly group, participant counts of 3 and 0 were reported.
- For the Dose Escalation 60 mg PO Twice Weekly group, participant counts of 3 and 0 were reported.
- For the Dose Escalation 90 mg PO Twice Weekly group, participant counts of 5 and 0 were reported.
What this means
The results from this Phase 1 study provide crucial data for identifying the recommended Phase 2 dose of the combination therapy involving pembrolizumab and XL888 for patients with advanced gastrointestinal cancer. By assessing participant counts across various dose escalation and expansion cohorts for both pancreatic and colorectal cancer arms, the trial has helped to characterize the safety profile and tolerability of different dosing regimens. This information is essential for guiding the design of subsequent clinical trials, ensuring that future studies proceed with a dose that balances efficacy potential with acceptable toxicity.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT03095781, titled "Pembrolizumab and XL888 in Patients With Advanced Gastrointestinal Cancer", were posted on 2026-05-22 on clinicaltrials.gov.