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

ConditionsSolid TumoursSarcomaHNSCCNon Small Cell Lung CancerNSCLCColorectal Cancer (CRC)Myxofibrosarcoma (MFS)Solitary Fibrous TumorsDedifferentiated LiposarcomaUndifferentiated Pleomorphic Sarcoma (UPS)LeiomyosarcomaLeiomyosarcoma (LMS)Gastric Cancer (GC)Gastric Cancer Adenocarcinoma MetastaticGastric / Gastroesophageal Junction Adenocarcinoma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorEpkin

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Cohort 1: Sarcoma (fibrous sarcoma [myxofibrosarcoma or solitary fibrous tumor], dedifferentiated liposarcoma, undifferentiated pleomorphic sarcoma or pleomorphic sarcoma, or leiomyosarcoma), 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: NSCLC (squamous or adenomatous without EGFR/ALK mutations), with disease progression on a PD-(L)1 CPI regimen, and no more than 3 prior lines of systemic therapy. When known, PD-L1 status should be provided.

Cohort 3: CRC (Microsatellite stable or Microsatellite instability - low), and no more than 4 prior lines of systemic therapy.

Cohort 4: GC (gastric and gastro-esophageal junction adenocarcinoma), HER2-negative, planned to or currently receiving CPI monotherapy as maintenance of a first-line CPI + chemotherapy regimen, after chemotherapy cessation.

Disqualifiers

Chemotherapy, ADCs, or other antibodies < 21 days

Immunotherapy or cellular therapy < 28 days

Radiation therapy (palliative radiation for bone pain <48 hours; stereotactic or small field brain irradiation <7 days; all other radiation therapy <14 days)

TKI or any other anticancer therapy < 5 half-lives or < 7 days, whichever is longer

Trial design

Design model

Parallel

Treatments tested in this trial

  • OKN4395

    Drug

    OKN4395 oral dosing twice per day

  • Pembrolizumab

    Combination product

    200 mg IV every 3 weeks

  • Fasting

    Other intervention

    Fasting before first dose of OKN4395

  • Fed

    Other intervention

    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

Treatment groups

146 Participants
are divided into 7 treatment groups

7

Treatment groups

See each treatment group below.

Group A: Monotherapy Dose Escalation Phase (Phase 1a)Experimental treatment 1 intervention
Group B: Combination Dose Confirmation Phase (Phase 1a)Experimental treatment 2 interventions
Group C: Phase 1a Substudy 1Experimental treatment 4 interventions
Group D: Phase 1b Cohort 1: SarcomaExperimental treatment 1 intervention
Group E: Phase 1b Cohort 2: Non-Small Cell Lung CancerExperimental treatment 2 interventions
Group F: Phase 1b Cohort 3: Colorectal CancerExperimental treatment 2 interventions
Group G: Phase 1b Cohort 4: Gastric CancerExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Incidence of DLTs in participants treated with OKN4395 as monotherapy and in combination with pembrolizumab. (Phase 1a)

DLTs = dose-limiting toxicities

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
2

Incidence and severity of TEAEs in participants treated with OKN4395 as a monotherapy and in combination with pembrolizumab in solid tumors. (Phase 1a)

TEAEs = treatment-emergent adverse events

Time frame
From enrolment of the first participant to the end of Phase 1a; up to 27 months
3

Incidence and severity of SAEs in participants treated with OKN4395 as a monotherapy and in combination with pembrolizumab in solid tumors. (Phase 1a)

SAEs = serious adverse events

Time frame
From enrolment of the first participant to the end of Phase 1a; up to 27 months
4

Incidence of dose interruptions, dose reductions, and dose intensities in participants treated with OKN4395 as a monotherapy and in combination with pembrolizumab in solid tumors. (Phase 1a)

Time frame
From enrolment of the first participant to the end of Phase 1a; up to 27 months

Secondary outcomes

1

To assess the overall response rate in participants treated with OKN4395 as monotherapy and in combination with pembrolizumab in selected cancer types. (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
2

To assess the disease control rate at >=12 weeks in participants treated with OKN4395 as monotherapy and in combination with pembrolizumab in selected cancer types. (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
3

To assess the duration of response in participants treated with OKN4395 as monotherapy and in combination with pembrolizumab in selected cancer types. (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
4

To assess the progression-free survival in participants treated with OKN4395 as monotherapy and in combination with pembrolizumab in selected cancer types. (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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Epkin

Lead sponsor

Precision For Medicine

Collaborator

Source ClinicalTrials.gov
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