RecruitingPhase 1

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

United States, Australia166 participantsStarted 2025-01-23

Plain-language 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.

Who can participate

Age range18 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. Histologically or cytologically confirmed disease, locally advanced or metastatic:
✓. ECOG performance status of 0 or 1.
✓. Recovery from any medically relevant AE/irAE from previous treatment regimen (defined as recovery to Grade ≤1 level per CTCAE v 5.0 before Screening, or chronic, stable, Grade 2 AEs \[not worsened to Grade \>2 for \>3 months prior to screening\]).
✓. One or more new or growing tumor lesions amenable to a safe biopsy (at baseline, a suitable archival specimen obtained when not undergoing treatment and within 1 year \[Phase 1a\], or within 90 days and after the last administration of the previous systemic therapy \[Phase 1b\] is suitable). In addition (where applicable) an archival tumor biopsy collected before the start of the first-line treatment in the metastatic setting is requested (but optional).
✓. At least one target lesion measurable by RECIST 1.1 as noted by local investigators/radiologists.
✓. The ability to swallow and retain OKN4395 as an oral medication without significant gastrointestinal abnormalities that might alter absorption.
✓. The willingness and ability to comply with the food effect (Phase 1b Cohort 1), or gastric pH effect (Phase 1b Cohort 2) evaluation randomizations and requirements.
✓

What they're measuring

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

Timeframe: From enrolment of the first participant until the end of Phase 1a or until the DLT threshold is reached; up to 27 months

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

Timeframe: From enrolment of the first participant to the end of Phase 1a; up to 27 months

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

Timeframe: From enrolment of the first participant to the end of Phase 1a; up to 27 months

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)

Timeframe: From enrolment of the first participant to the end of Phase 1a; up to 27 months

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

Timeframe: From enrolment of the first participant to the end of Phase 1a; up to 27 months

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

Trial details

NCT IDNCT06789172

SponsorEpkin

Sponsor typeINDUSTRY

Study typeINTERVENTIONAL

Primary completion2028-07

Contact for this trial

Epkin

+31 617676896 clinicaltrials@owkin.com

View on ClinicalTrials.gov More Solid Tumours trials

Plain-language summary

Who can participate

Age range18 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. Histologically or cytologically confirmed disease, locally advanced or metastatic:
✓. ECOG performance status of 0 or 1.
✓. Recovery from any medically relevant AE/irAE from previous treatment regimen (defined as recovery to Grade ≤1 level per CTCAE v 5.0 before Screening, or chronic, stable, Grade 2 AEs \[not worsened to Grade \>2 for \>3 months prior to screening\]).
✓. One or more new or growing tumor lesions amenable to a safe biopsy (at baseline, a suitable archival specimen obtained when not undergoing treatment and within 1 year \[Phase 1a\], or within 90 days and after the last administration of the previous systemic therapy \[Phase 1b\] is suitable). In addition (where applicable) an archival tumor biopsy collected before the start of the first-line treatment in the metastatic setting is requested (but optional).
✓. At least one target lesion measurable by RECIST 1.1 as noted by local investigators/radiologists.
✓. The ability to swallow and retain OKN4395 as an oral medication without significant gastrointestinal abnormalities that might alter absorption.
✓. The willingness and ability to comply with the food effect (Phase 1b Cohort 1), or gastric pH effect (Phase 1b Cohort 2) evaluation randomizations and requirements.
✓