Actively Recruiting
A Phase 1, First-in-human Study of OKN4395 and Pembrolizumab in Patients With Solid Tumors
Led by Epkin · Updated on 2025-09-05
166
Participants Needed
10
Research Sites
188 weeks
Total Duration
On this page
Sponsors
E
Epkin
Lead Sponsor
P
Precision For Medicine
Collaborating Sponsor
AI-Summary
What this Trial Is About
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.
CONDITIONS
Official Title
A Phase 1, First-in-human Study of OKN4395 and Pembrolizumab in Patients With Solid Tumors
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Adults with histologically or cytologically confirmed locally advanced or metastatic solid tumors with COX2-associated immunosuppressive pathway and no available or tolerated standard treatments (Phase 1a)
- For Phase 1b, patients with selected cancers (sarcoma, pancreatic adenocarcinoma, NSCLC, colorectal cancer, HNSCC) who have exhausted all appropriate authorized treatment options
- Sarcoma patients with no more than 3 prior systemic therapies; solitary fibrous tumor patients may be included without prior treatment if appropriate
- Pancreatic adenocarcinoma patients with no more than 3 prior systemic therapies
- NSCLC patients with prior platinum-based chemotherapy and PD-(L)1 therapy, no more than 3 prior systemic therapies
- Colorectal cancer patients with no more than 4 prior systemic therapies
- HNSCC patients with prior PD-(L)1 therapy, no more than 3 prior systemic therapies
- ECOG performance status of 0 or 1
- Recovery from relevant adverse events from previous treatments
- Presence of biopsy-amenable new or growing tumor lesions or suitable archival specimens
- At least one measurable target lesion by RECIST 1.1
- Ability to swallow and retain OKN4395 oral medication without significant gastrointestinal issues
- Willingness and ability to comply with food or gastric pH effect evaluation randomizations (Phase 1b Cohorts 1 and 2)
- Adequate blood, kidney, and liver function based on local lab assessments
You will not qualify if you...
- Recent anticancer therapy within specified timeframes before study drug (chemotherapy or antibodies within 21 days; immunotherapy or cellular therapy within 28 days; specific radiation therapy within 48 hours to 14 days; TKIs or other anticancer therapies within 5 half-lives or 7 days)
- Central nervous system metastases that are progressive, symptomatic, or require immunosuppressive treatment
- Active infections requiring intravenous therapy
- Unstable chronic obstructive pulmonary disease
- Known active hepatitis B, hepatitis C, or HIV infection with insufficient immune control
- History of bleeding disorders or recent gastrointestinal bleeding within 2 years
- Untreated Helicobacter pylori infection
- Use of drugs affecting gastrointestinal pH within 7 days or 12 hours before first OKN4395 dose
- Recent use of systemic steroids or corticosteroids within 14 days before study drug
- History or active autoimmune disease needing systemic treatment in past 2 years for combination therapy participants
- Recent use of NSAIDs, COX2 inhibitors, or synthetic prostaglandins within 5 half-lives before first OKN4395 dose (low-dose aspirin allowed)
- Treatment with strong CYP and UGT enzyme inhibitors or inducers within 14 days before first dose
- QTcF interval over 450 ms on ECG
- Known allergy to OKN4395 or pembrolizumab ingredients
- Pregnant or breastfeeding women; women of childbearing potential must test negative for pregnancy
- Any other active malignancy needing systemic therapy within 2 years except certain exceptions
- Any medical or surgical condition that could interfere with study participation or safety as judged by the physician
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 10 locations
1
Precision NextGen Oncology and Research Center
Beverly Hills, California, United States, 90212
Actively Recruiting
2
Sarcoma Oncology Center
Santa Monica, California, United States, 90403
Actively Recruiting
3
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Actively Recruiting
4
Chris O'Brien Lifehouse
Sydney, New South Wales, Australia
Actively Recruiting
5
Linear Clinical Research
Perth, Western Australia, Australia, 6009
Actively Recruiting
6
The Beatson
Glasgow, United Kingdom
Actively Recruiting
7
Leicester Royal Infirmary
Leicester, United Kingdom, LE1 5WW
Actively Recruiting
8
University College London Hospital
London, United Kingdom
Actively Recruiting
9
The Christie
Manchester, United Kingdom
Actively Recruiting
10
Churchill Hospital
Oxford, United Kingdom
Actively Recruiting
Research Team
E
Epkin
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
9
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here