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

Conditions

• Colorectal Cancer (CRC)
• Dedifferentiated Liposarcoma
• Gastric / Gastroesophageal Junction Adenocarcinoma
• Gastric Cancer (GC)
• Gastric Cancer Adenocarcinoma Metastatic
• HNSCC
• Leiomyosarcoma
• Leiomyosarcoma (LMS)
• Myxofibrosarcoma (MFS)
• NSCLC
• Non Small Cell Lung Cancer
• Sarcoma
• Solid Tumours
• Solitary Fibrous Tumors
• Undifferentiated Pleomorphic Sarcoma (UPS)

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• OKN4395 — DRUG
  OKN4395 oral dosing twice per day
• Pembrolizumab — COMBINATION_PRODUCT
  200 mg IV every 3 weeks
• Fasting — OTHER
  Fasting before first dose of OKN4395
• Fed — OTHER
  Food provided to patient before first OKN4395 dose
• H2 Receptor Antagonist — DRUG
  Famotidine 20 mg IV (as a slow push over 2 minutes) administered 3 hours prior to OKN4395

Study Details

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 participants 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 1a also includes a parallel substudy (Substudy 1) consisting of at least 12 participants, aiming to test the effect of food and stomach acid on the levels of OKN4395 in the blood as well as its tolerability. 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 4 cohorts: Cohort 1 in sarcoma (OKN4395 alone), Cohort 2 in non-small cell lung cancer (NSCLC), Cohort 3 in colorectal cancer, and Cohort 4 in gastric cancer (GC), with cohorts 2 to 4 in combination with pembrolizumab. The overall study will enrol approximately 146 participants with up to 54 participants to receive OKN4395 alone and 12 participants to receive OKN4395 in combination with pembrolizumab in Part 1a, and 80 participants in Part 1b split: 20 on monotherapy and 60 on combination therapy. The study will be conducted in the US, Australia, UK and in the EU.

Key Dates

Start date

Jan 23, 2025

Status verified

Jun 2026

Primary completion

Jul 31, 2028

Completion

Sep 30, 2028

Study Design

Enrollment

146 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Monotherapy Dose Escalation Phase (Phase 1a)
  The Monotherapy Escalation Phase will include increasing doses of OKN4395 alone in patients with solid tumors with a COX2-associated immunosuppressive pathway.
• Experimental: Combination Dose Confirmation Phase (Phase 1a)
  The Combination Dose Confirmation Phase will include increasing or decreasing doses of OKN4395 in combination with pembrolizumab in patients with solid tumors with a COX2-associated immunosuppressive pathway. The first dose level used will be 1 level below the identified OBD/MTD for monotherapy. Subsequent dose levels tested will either be increased or decreased in response to observed toxicity.
• Experimental: Phase 1a Substudy 1
  Participants will receive 3 doses of OKN4395 in a fasted, fed, and high gastric pH state (once each) with a washout period inbetween. Each state and dose will occur within the first 8 days of treatment (C1 D1-D8). The sequence of these predose conditions will be randomized. After C1 D8, participants will receive OKN4395 as monotherapy twice per day, in line with the dose escalation portion of the study, for the remainder of treatment. The high pH state is achieved through co-administration of the H2 receptor antagonist, famotidine, administered 2 hours before OKN4395 at a dose of 20mg intravenously.
• Experimental: Phase 1b Cohort 1: Sarcoma
  OKN4395 (OBD/MTD monotherapy dose)
• Experimental: Phase 1b Cohort 2: Non-Small Cell Lung Cancer
  OKN4395 (OBD/MTD combination dose) in combination with pembrolizumab
• Experimental: Phase 1b Cohort 3: Colorectal Cancer
  OKN4395 (OBD/MTD combination dose) in combination with pembrolizumab
• Experimental: Phase 1b Cohort 4: Gastric Cancer
  OKN4395 (OBD/MTD combination dose) in combination with pembrolizumab

Primary Outcome Measure

Incidence of DLTs in participants treated with OKN4395 as monotherapy and in combination with pembrolizumab. (Phase 1a) [ Time Frame: From enrolment of the first participant until the end of Phase 1a or until the DLT threshold is reached; up to 27 months ]

Central Contacts

• Epkin
  +33 787922617
  [email protected]

Locations (3)

Find similar trials in Beverly Hills, CA

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