A Phase 1, First-in-human Study of OKN4395 and Pembrolizumab in Patients With Solid Tumors
Trial Parameters
Brief 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, OKN4395 and metabolites (broken-down substances) of OKN4395 levels 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) or with pembrolizumab (combination therapy) administered on day 1 of each 21-day cycle 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 completes 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 evaluate OKN4395 alone and in combination with pembrolizumab administered on day 1 of each 21-day cycle in patients with selected cancer types. Part 1b will comprise 5 cohorts: Cohort 1 in sarcoma (OKN4395 alone), Cohort 2 pancreatic adenocarcinoma (OKN4395 alone), Cohort 3 in non-small cell lung cancer (NSCLC), Cohort 4 in colorectal cancer, and Cohort 5 in head \& neck squamous cell carcinoma (HNSCC), with cohorts 3 to 5 in combination with pembrolizumab. The monotherapy expansion Cohort 1 will also be used to explore the effect of food on the levels of OKN4395 in the blood. Similarly, Cohort 2 will be used to explore the effect of gastric pH on the levels of OKN4395 in the blood. The overall study will enrol approximately 166 participants with up to 54 participants to receive OKN4395 alone and 12 participants to receive OKN4395 in combination with pembrolizumab in Part 1a, and 100 participants in Part 1b split: 40 on monotherapy and 60 on combination therapy. The study will be conducted in the US, Australia, UK and in the EU.
Eligibility Criteria
Inclusion Criteria: 1. Histologically or cytologically confirmed disease, locally advanced or metastatic: For Phase 1a: Solid tumor with a COX2-associated immunosuppressive pathway, for which standard treatment options are not available, no longer effective, refused or not tolerated. For Phase 1b: For all cohorts, in the opinion of the investigator, all appropriate authorised treatment options should be exhausted * Cohort 1: Sarcoma (fibrous sarcoma \[myxofibrosarcoma or solitary fibrous tumor\], dedifferentiated liposarcoma, undifferentiated pleomorphic sarcoma or pleomorphic sarcoma), that is either refractory to or progressing on standard of care, with no more than 3 prior lines of systemic therapy. Patients with a solitary fibrous tumor can be included in the study without prior treatment if, in the investigator's opinion, it is in the participant's best interest and no established standard of care exists or is available. * Cohort 2: Pancreatic adenocarcinoma, with no more than 3 p