Solid Tumors > OKN4395

OKN4395 + Pembrolizumab for Solid Tumors (INVOKE Trial)

Recruiting in Palo Alto (17 mi)

+2 other locations

Age: 18+

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Epkin

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of 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 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 4 cohorts: cohort 1 in sarcoma (OKN4395 alone), cohort 2 in non-small cell lung cancer (NSCLC), cohort 3 in mesothelioma, and cohort 4 in head \& neck squamous cell carcinoma (HNSCC), with cohorts 2 to 4 in combination with pembrolizumab. The monotherapy expansion cohort (Cohort 1) will also be used to choose the optimal dose for further development and to explore the effect of food 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, in the UK and in the EU.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain medications like systemic steroids, NSAIDs, and drugs affecting gastrointestinal pH or specific enzymes must be stopped before starting the trial. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug OKN4395 + Pembrolizumab for solid tumors?

Research shows that pembrolizumab, one of the drugs in this treatment, has been effective in treating various cancers like advanced melanoma and non-small-cell lung cancer by helping the immune system attack cancer cells.

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Is the combination of OKN4395 and Pembrolizumab safe for humans?

Pembrolizumab has been studied in various cancers like ovarian, lung, and bone cancer, showing a safety profile that is generally acceptable, but it can have side effects like fatigue, rash, and diarrhea. However, specific safety data for the combination of OKN4395 and Pembrolizumab is not available in the provided research.

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What makes the drug OKN4395 + Pembrolizumab unique for treating solid tumors?

This treatment combines OKN4395 with pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells. Pembrolizumab is already used for various cancers, but combining it with OKN4395 may enhance its effectiveness, especially in tumors that are less responsive to immunotherapy alone.

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Eligibility Criteria

This trial is for patients with various solid tumors, including lung cancer and mesothelioma. Participants must have a type of tumor that the study targets and be willing to undergo treatment cycles every 21 days. Specific eligibility details are not provided but typically include factors like age, health status, and prior treatments.

Inclusion Criteria

My cancer is confirmed and has spread or is advanced.

My solid tumor cannot be treated with standard options.

I am fully active or can carry out light work.

I have a tumor that can be safely biopsied.

I can take pills without trouble and don't have major stomach issues.

Exclusion Criteria

My cancer has spread to my brain.

I am currently on IV medication for an infection.

I do not have active hepatitis B, C, or HIV.

I am not on drugs that affect stomach acid levels.

I am currently on a steroid treatment.

I am on medication for an autoimmune disease.

My COPD is not stable.

I have a history of bleeding disorders or stomach/intestinal bleeding.

Participant Groups

The trial tests OKN4395 alone or combined with pembrolizumab in treating solid tumors. It's split into two parts: Part 1a explores multiple doses; Part 1b focuses on selected cancers. Doses range from 10 mg to 450 mg twice daily over several levels.

Group I: Squamous NSCLC Experimental Treatment 2 Interventions

OKN4395 (OBD/MTD combination dose) in combination with pembrolizumab

Group II: Sarcoma food effect cohort 4 Experimental Treatment 2 Interventions

Fed First Dose and Alternative Dose

Group III: Sarcoma food effect cohort 3 Experimental Treatment 2 Interventions

Fasted First Dose and Alternative Dose

Group IV: Sarcoma food effect cohort 2 Experimental Treatment 2 Interventions

Fed First Dose and OBD/MTD Dose

Group V: Sarcoma food effect cohort 1 Experimental Treatment 2 Interventions

Fasted First Dose and OBD/MTD Dose

Group VI: Malignant Mesothelioma Experimental Treatment 2 Interventions

OKN4395 (OBD/MTD combination dose) in combination with pembrolizumab

Group VII: HNSCC Experimental Treatment 2 Interventions

OKN4395 (OBD/MTD combination dose) in combination with pembrolizumab

Group VIII: Dose Level 9 Experimental Treatment 1 Intervention

170 mg BID

Group IX: Dose Level 8 Experimental Treatment 1 Intervention

130 mg BID

Group X: Dose Level 7 Experimental Treatment 1 Intervention

100 mg BID

Group XI: Dose Level 6 Experimental Treatment 1 Intervention

70 mg BID

Group XII: Dose Level 5 Experimental Treatment 1 Intervention

50 mg BID

Group XIII: Dose Level 4 Experimental Treatment 1 Intervention

30 mg BID

Group XIV: Dose Level 3 Experimental Treatment 1 Intervention

20 mg BID

Group XV: Dose Level 2 Experimental Treatment 1 Intervention

20/10 mg mane/nocte

Group XVI: Dose Level 13 Experimental Treatment 1 Intervention

450 mg BID

Group XVII: Dose Level 12 Experimental Treatment 1 Intervention

350 mg BID

Group XVIII: Dose Level 11 Experimental Treatment 1 Intervention

280 mg BID

Group XIX: Dose Level 10 Experimental Treatment 1 Intervention

220 mg BID

Group XX: Dose Level 1 Experimental Treatment 1 Intervention

10 mg BID

Group XXI: Combination Therapy phase 1a cohort 2 Experimental Treatment 2 Interventions

OKN4395 (at the OBD/MTD for monotherapy) in combination with pembrolizumab

Group XXII: Combination Therapy phase 1a cohort 1 Experimental Treatment 2 Interventions

OKN4395 (at one dose level below the OBD/MTD for monotherapy) in combination with pembrolizumab

Find A Clinic Near You

Research locations nearby Select from list below to view details:

Precision NextGen Oncology and Research Center Beverly Hills, CA

Sarcoma Oncology Center Santa Monica, CA

Who is running the clinical trial?

Epkin Lead Sponsor

Precision For Medicine Industry Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. [2019] To evaluate safety, tolerability, and antitumor activity of pembrolizumab monotherapy in patients with programmed death ligand 1 (PD-L1)-expressing advanced ovarian cancer enrolled in the multicohort, phase Ib KEYNOTE-028 trial.

2. United States pubmed.ncbi.nlm.nih.gov

Clinical Efficacy and Safety Analysis of PD-1/PD-L1 Inhibitor vs. Chemotherapy in the Treatment of Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. [2023] To systematically evaluate the efficacy and safety of pembrolizumab (PD-1/PD-L inhibitor) and adjuvant chemotherapy to treat NSCLC and provide evidence-based reference for clinical use.

3. England pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. [2018] Pembrolizumab is a fully humanized anti-PD-1 agent currently approved for the treatment of advanced melanoma and pretreated non-small-cell lung cancer (NSCLC).

4. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017] Pembrolizumab, a humanized monoclonal antibody IgG4 anti-PD-1, having offered promising results in patients suffering from non-small cell lung cancer metastatic and heavily pretreated.

5. United States pubmed.ncbi.nlm.nih.gov

Association of Pembrolizumab With Tumor Response and Survival Among Patients With Advanced Melanoma. [2022] The programmed death 1 (PD-1) pathway limits immune responses to melanoma and can be blocked with the humanized anti-PD-1 monoclonal antibody pembrolizumab.

6. United States pubmed.ncbi.nlm.nih.gov

First-line pembrolizumab for non-small cell lung cancer patients with PD-L1 ≥50% in a multicenter real-life cohort: The PEMBREIZH study. [2021] The KEYNOTE-024 trial demonstrated that pembrolizumab, a PD-1 inhibitor, significantly improves progression-free survival (PFS) and overall survival (OS) in selected patients with previously untreated advanced non-small cell lung cancer (NSCLC) with a PD-L1 tumor proportion score (TPS) ≥50% and without EGFR/ALK aberrations. The main aim of this study was to report the efficacy and safety profile of pembrolizumab in real-life conditions.

7. Germany pubmed.ncbi.nlm.nih.gov

Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial. [2022] To evaluate the activity and safety of the PD-1 antibody pembrolizumab in adult patients with advanced osteosarcoma.

8. Germany pubmed.ncbi.nlm.nih.gov

Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50. [2020] Single-agent pembrolizumab represents the standard first-line option for metastatic non-small-cell lung cancer (NSCLC) patients with a PD-L1 (programmed death-ligand 1) expression of ≥ 50%.

9. England pubmed.ncbi.nlm.nih.gov

Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. [2022] The anti-programmed-death-receptor-1 (PD-1) antibody pembrolizumab has shown potent antitumour activity at different doses and schedules in patients with melanoma. We compared the efficacy and safety of pembrolizumab at doses of 2 mg/kg and 10 mg/kg every 3 weeks in patients with ipilimumab-refractory advanced melanoma.

10. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical utility of pembrolizumab in the management of advanced solid tumors: an evidence-based review on the emerging new data. [2023] Pembrolizumab is a full-length human immunoglobulin G4 (IgG4) monoclonal antibody directed against the immune checkpoint PD-1 to remove its binding with PD-L1 and thus to restore an anti-tumor immune response of T cells. Pembrolizumab is one of the most advanced immune checkpoint inhibitors for cancer care. Apart from rare and serious adverse effects, its favorable tolerance profile enables to treat fragile patients who have often no other choice than best supportive care. The effective retained dose of pembrolizumab is a venous administration of 200 mg every 3 weeks until disease progression, intolerance or up to 24 months. Pembrolizumab has already proven its efficacy and thus obtained marketing authorization in so-called hot or hypermutated tumors or tumors expressing PD-L1 such as melanomas, non-small cell lung cancers, urothelial carcinomas, cervical cancer, etc. Pembrolizumab is also authorized in the United States in the treatment of mismatch repair-deficient tumors or with microsatellite instability. The current challenge is to expand its use in tumor types that are supposed to be less immunogenic, for example, by attempting to warm up the tumor microenvironment, or by combining pembrolizumab with other molecules. An acceptable toxicity profile of such combinations remains to explore. We review here the current indications of this drug, the main prognostic and predictive factors of its efficacy as well as the potential forthcoming indications.