A Phase 1, First-in-human Study of OKN4395 and Pembrolizumab in Patients With Solid Tumors

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.

Conditions

• Solid Tumours
• Sarcoma
• HNSCC
• Non Small Cell Lung Cancer
• Head and Neck Squamous Cell Carcinoma
• NSCLC
• Pancreatic Adenocarcinoma
• Colorectal Cancer (CRC)
• Myxofibrosarcoma (MFS)
• Solitary Fibrous Tumors
• Dedifferentiated Liposarcoma
• Undifferentiated Pleomorphic Sarcoma (UPS)

Interventions

DRUG

OKN4395

OKN4395 oral dosing twice per day

COMBINATION_PRODUCT

Pembrolizumab

200 mg IV every 3 weeks

OTHER

Fasting

Fasting before first dose of OKN4395

OTHER

Fed

Food provided to patient before first OKN4395 dose

DRUG

H2 Receptor Antagonist

Famotidine 20 mg IV (as a slow push over 2 minutes) administered 3 hours prior to OKN4395

Sponsors & Collaborators

• Precision For Medicine

  collaborator INDUSTRY

• Epkin

  lead INDUSTRY

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-01-23

Primary Completion

2028-07-31

Completion

2028-09-30

FDA Drug

Yes

Countries

• United States
• Australia
• United Kingdom

Study Locations