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Investigating OKN4395 and Pembrolizumab for Solid Tumors

A Phase 1, Open-label, Multicenter, Dose-escalation and Cohort Expansion Study of OKN4395, a Triple Antagonist of EP2, EP4, and DP1 Prostanoid Receptors, as Monotherapy and in Combination With Pembrolizumab, in Patients With Advanced Solid Tumors

Phase 1 Interventional Epkin · NCT06789172

This study is testing a new drug called OKN4395, alone and with another drug called pembrolizumab, to see if it can help people with solid tumors who have run out of other treatment options.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment166 (estimated)
Ages18 Years and up
SexAll
SponsorEpkin Industry-sponsored
Drugs / interventionspembrolizumab, chemotherapy, Immunotherapy, Radiation, prednisone
Locations10 sites (Beverly Hills, California and 9 other locations)
Trial IDNCT06789172 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety and tolerability of the drug OKN4395, both alone and in combination with pembrolizumab, in patients with solid tumors. The study is divided into two parts, with Part 1a focusing on multiple doses of OKN4395 administered to patients with various solid tumors who have exhausted standard treatment options. Participants will receive treatment in 21-day cycles until disease progression or discontinuation. The study will also assess the antitumor activity of the drug and its metabolites in the blood.

Who should consider this trial

Good fit: Ideal candidates include patients with histologically confirmed solid tumors, particularly those with sarcoma or pancreatic adenocarcinoma, who have exhausted standard treatment options.

Not a fit: Patients with solid tumors for which effective standard treatments are available or those who do not meet the specific inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with solid tumors that have limited or no effective therapies available.

How similar studies have performed: Other studies have shown promise in using combination therapies for solid tumors, but the specific approach of combining OKN4395 with pembrolizumab is novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Histologically or cytologically confirmed disease, locally advanced or metastatic:

   For Phase 1a:

   Solid tumor with a COX2-associated immunosuppressive pathway, for which standard treatment options are not available, no longer effective, refused or not tolerated.

   For Phase 1b:

   For all cohorts, in the opinion of the investigator, all appropriate authorised treatment options should be exhausted
   * Cohort 1: Sarcoma (fibrous sarcoma \[myxofibrosarcoma or solitary fibrous tumor\], dedifferentiated liposarcoma, undifferentiated pleomorphic sarcoma or pleomorphic sarcoma), 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: Pancreatic adenocarcinoma, with no more than 3 prior lines of systemic therapy. When known, KRAS and BRCA status should be provided.
   * Cohort 3: NSCLC (squamous or adenomatous without EGFR/ALK mutations), with previous platinum-based chemotherapy and a previous PD-(L)1 CPI regimen (unless not eligible/unwilling to receive such therapies), and no more than 3 prior lines of systemic therapy. When known, PD-L1 status should be provided.
   * Cohort 4: CRC (Microsatellite stable or Microsatellite instability - low), and no more than 4 prior lines of systemic therapy.
   * Cohort 5: HNSCC (oral cavity, oropharynx, larynx, hypopharynx), with a previous regimen containing a PD-(L)1 CPI (unless not eligible/unwilling to receive such therapies), and no more than 3 prior lines of systemic therapy. When known, PD-L1 and HPV status should be provided.
2. ECOG performance status of 0 or 1.
3. 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 \[not worsened to Grade \>2 for \>3 months prior to screening\]).
4. 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).
5. At least one target lesion measurable by RECIST 1.1 as noted by local investigators/radiologists.
6. The ability to swallow and retain OKN4395 as an oral medication without significant gastrointestinal abnormalities that might alter absorption.
7. 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.
8. Adequate hematologic, renal, and hepatic function (based on local laboratory assessments):

   1. Hematological variables: absolute neutrophil counts ≥1.5 × 109 /L, platelet counts ≥75 × 109 /L, and hemoglobin ≥8 g/dL
   2. Renal variables: creatinine clearance ≥ 60 mL/min1
   3. Hepatic variables: total serum bilirubin ≤1.5 × ULN, AST and ALT ≤3 × ULN, and ALP ≤2.5 × ULN; except for hyperbilirubinemia of Gilbert's syndrome (participants with Gilbert's syndrome can be included if total serum bilirubin ≤5× ULN and direct bilirubin ≤1.5 x ULN)
   4. Serum albumin ≥30 g/L

Exclusion Criteria:

1. Ongoing or recent anticancer therapy within the following timeframe prior to first dose of study drug:

   1. Chemotherapy, ADCs, or other antibodies \< 21 days
   2. Immunotherapy or cellular therapy \< 28 days
   3. Radiation therapy (palliative radiation for bone pain \<48 hours; stereotactic or small field brain irradiation \<7 days; all other radiation therapy \<14 days)
   4. TKI or any other anticancer therapy \< 5 half-lives or \< 7 days, whichever is longer
2. Central nervous system metastasis (radiologically progressive, or clinically symptomatic, or requiring immunosuppressive therapies \[including low dose steroids\]).
3. Any active infection (bacterial, viral, fungal) requiring IV systemic therapy.
4. Unstable COPD defined as frequent or severe exacerbations per investigator discretion.
5. Known active HBV or HCV infection or positive test(s) as per CDC guidance (Centers for Disease Control and Prevention, 2023, 2024) or HIV infection with CD4 lymphocyte count \<350 cells/μL at time of Screening, or failure to achieve and maintain virologic suppression defined as confirmed HIV RNA level \< 50 or lower limit of detection by the local available assay at time of Screening and for at least 12 weeks prior to Screening. No testing is required unless medically indicated or mandated by local authorities.
6. Known history of bleeding disorders, INR ≥1.5 × ULN at screening (or INR and/or aPTT within therapeutic range if on anticoagulation therapy), or a history of gastrointestinal bleeding (inflammatory, ulcerative, or diverticular) within the last 2 years.
7. Known H. pylori infection without proof of eradication at least 2 months prior to screening.
8. Systemic treatment with any drug known to impact gastrointestinal pH within 7 days (PPIs) or 12 hours (H2 antagonists) of first dose of OKN4395.
9. Acute treatment with any systemic steroid therapy (\>10 mg prednisone equivalent), or any corticosteroid medication within 14 days of first dose of OKN4395 for any condition.
10. For participants planned to receive combination therapy: Ongoing and history of active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Any replacement therapy (i.e. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed. Participants with hyperthyroidism or hypothyroidism but that are stable on hormone replacement are also allowed.
11. Systemic treatment with NSAIDs, COX2 inhibitors, or synthetic prostaglandins within 5 half-lives prior to the first dose of OKN4395 (acetylsalicylic acid ≤ 160 mg/day, or 325 mg ≤ 3 times/week is permitted).
12. Systemic treatment with strong inhibitors/inducers of CYP and UGT enzymes within 14 days of first dose of OKN4395.
13. QTcF interval of \> 450 ms based on mean of the central triplicate readings.
14. Known hypersensitivity to any excipients of the OKN4395 formulation or pembrolizumab (for combination cohorts).
15. Pregnant or lactating women. Women of childbearing potential must have a negative serum pregnancy test at screening and have a negative a urine dipstick pregnancy test prior to the initiation of study treatment (can be done on C1-D1 visit).
16. Evidence of any other active malignancy requiring systemic therapy within the 2 years prior to Screening. (Exceptions: non-melanoma skin cancer, in situ melanoma, in situ cervical cancer, ductal carcinoma in situ of the breast, or localized and presumed cured prostate cancer; participants on long-term anti-hormonal therapy for a prior malignancy are allowed if the malignancy has not been active within the prior 2 years).
17. History or current evidence of any condition, surgical or medical therapy, or laboratory abnormalities that might confound the results of the study, make study drug administration hazardous, interfere with the participant's involvement for the full duration of the study, or make it difficult to monitor AEs such that, in the opinion of the treating physician, it is not in the best interest of the participant to participate

Where this trial is running

Beverly Hills, California and 9 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Solid TumoursSarcomaHNSCCNon Small Cell Lung CancerHead and Neck Squamous Cell CarcinomaNSCLCPancreatic AdenocarcinomaColorectal Cancer
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.