A phase 1, first-in-human study of OKN4395 and pembrolizumab in patients with solid tumors
Research type
Research Study
Full title
A Phase 1, open-label, multicenter, dose-escalation and cohort expansion study of OKN4395, a triple antagonist of EP2, EP4, and DP1 prostanoid receptors, as monotherapy and in combination with pembrolizumab, in patients with advanced solid tumors
IRAS ID
1010615
Contact name
Luke Kuttschreuter
Contact email
Sponsor organisation
Epkin
Clinicaltrials.gov Identifier
Research summary
The purpose of this study is to investigate the study drug, OKN4395, administered alone and in combination with pembrolizumab.
The overall objectives of this study are to determine the safety and tolerability (degree to which side effects of a drug can be tolerated) of OKN4395 alone and in combination with pembrolizumab, the levels of OKN4395 and metabolites (broken-down substances) in the blood, and antitumor activity of OKN4395 alone and in combination with pembrolizumab. This study will be split into 2 parts.
Part 1a will look at multiple doses of OKN4395 either alone (monotherapy for 54 participants) or with pembrolizumab (combination therapy for 12 participants) in patients with solid tumors until the participant has disease progression or discontinues for any reason. The dose of OKN4395 will be increased, after each group of 3 or more patients complete their first 3 weeks of treatment and their data is evaluated for safety, with a planned dose range from 10 mg twice a day to 450 mg twice a day through 13 dose levels.
Part 1b will comprise 5 cohorts of 20 participants each with selected cancer types: cohort 1 in sarcoma, cohort 2 in pancreatic adenocarcinoma, cohort 3 in non-small cell lung cancer, cohort 4 in colorectal carcinoma, and cohort 5 in head & neck squamous cell carcinoma. Cohorts 1 and 2 will receive OKN4395 alone and cohorts 3 to 5 will receive OKN4395 in combination with pembrolizumab. Cohort 1 will also be used to explore the effect of food on the levels of OKN4395 in the blood. Cohort 2 will also be used to explore the effect of gastric pH on the levels of OKN4395 in the blood. Half of the participants in Cohort 2 will receive OKN4395 with famotidine, while the other half will receive OKN4395 alone.
The overall study will enrol approximately 166 participants with up to 66 participants in Part 1a, and 100 participants in Part 1b split. The study will be conducted in the US, Australia, the UK and in the EU.REC name
London - City & East Research Ethics Committee
REC reference
25/LO/0019
Date of REC Opinion
26 Feb 2025
REC opinion
Further Information Favourable Opinion