OKN4395 + Pembrolizumab for Solid Tumors

(INVOKE Trial)

Recruiting at 9 trial locations

Overseen By Epkin

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Epkin

Must not be taking: PPIs, H2 antagonists, Steroids, NSAIDs

Disqualifiers: CNS metastasis, Active infection, COPD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 42

166 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment called OKN4395, used alone or with pembrolizumab (an immunotherapy drug), to assess its safety and effectiveness against solid tumors such as sarcoma, pancreatic cancer, lung cancer, colorectal cancer, and head and neck cancer. Researchers aim to understand how the drug is tolerated and how it behaves in the body. Individuals with these cancers who have not found success with other treatments might find this trial suitable. Participants must be able to swallow pills and should not have certain infections or recent cancer treatments. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have tested the new drug OKN4395 for safety, but research remains in the early stages. This trial marks the first time the drug is being tested in humans, so detailed safety information is not yet available. Researchers are examining its tolerance both alone and in combination with another drug, pembrolizumab.

Pembrolizumab is used in other cancer treatments and is generally considered safe, though it can sometimes cause side effects like tiredness or skin reactions. As a Phase 1 trial, the primary goal is to assess safety and side effects, so the complete safety profile of OKN4395 is still under development. Researchers are cautiously starting with low doses to monitor for any issues. The trial will provide crucial information on how people respond to the drug and whether it causes any problems. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about OKN4395, especially in combination with pembrolizumab, because it offers a novel approach to tackling solid tumors linked to an immunosuppressive pathway called COX2. Unlike standard treatments that may not specifically target this pathway, OKN4395 directly interacts with it, potentially enhancing the immune response against cancer cells. Additionally, the study is exploring different ways this drug can be administered, such as with or without food or in combination with H2 receptor antagonists like famotidine, which could optimize its effectiveness and offer more personalized treatment options. These unique features make OKN4395 a promising candidate for improving outcomes in difficult-to-treat cancers like sarcoma, pancreatic, and non-small cell lung cancer.

What evidence suggests that this trial's treatments could be effective for solid tumors?

Research has shown that OKN4395 is a promising new drug for treating solid tumors. It blocks certain parts of the tumor that help it hide from the immune system, potentially enhancing the body's natural defenses against cancer. In this trial, some participants will receive OKN4395 alone. Studies indicate that it may change the tumor environment, making it easier to treat. Other participants will receive OKN4395 combined with pembrolizumab, a drug already used for cancers like melanoma and lung cancer. Early findings suggest that this combination could significantly boost the immune system's response to tumors. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

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

At least one target lesion measurable by RECIST 1.1

My cancer is confirmed and has spread or is advanced.

My solid tumor cannot be treated with standard options.

Exclusion Criteria

My cancer has spread to my brain.

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

Known H. pylori infection without proof of eradication

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-escalation Treatment

Participants receive multiple doses of OKN4395 either alone or with pembrolizumab, with dose escalation based on safety evaluations

21-day cycles, up to 27 months

Visits every 21 days

Cohort Expansion Treatment

Evaluation of OKN4395 alone and in combination with pembrolizumab in specific cancer cohorts

21-day cycles, up to 27 months

Visits every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• OKN4395
• Pembrolizumab

Trial Overview 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.

How Is the Trial Designed?

Group I: Phase 1b Cohort 5: HNSCC Experimental Treatment 2 Interventions

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

Group II: Phase 1b Cohort 4: Colorectal Cancer Experimental Treatment 2 Interventions

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

Group III: Phase 1b Cohort 3: NSCLC Experimental Treatment 2 Interventions

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

Group IV: Phase 1b Cohort 2: Pancreas Gastric pH Effect (without H2RA) Experimental Treatment 1 Intervention

No co-administered H2RA (H2 receptor antagonist; famotidine) first dose, and OBD/MTD (mono) dose of OKN4395 as monotherapy for the remainder of treatment.

Group V: Phase 1b Cohort 2: Pancreas Gastric pH Effect (with H2RA) Experimental Treatment 2 Interventions

Co-administered H2RA (H2 receptor antagonist; famotidine) first dose, and OBD/MTD (mono) dose of OKN4395 as monotherapy for the remainder of treatment.

Group VI: Phase 1b Cohort 1: Sarcoma Food Effect (Fed) Experimental Treatment 2 Interventions

Fed first dose, and OBD/MTD (mono) dose of OKN4395 as monotherapy for the remainder of treatment.

Group VII: Phase 1b Cohort 1: Sarcoma Food Effect (Fasted) Experimental Treatment 2 Interventions

Fasted first dose, and OBD/MTD (mono) dose of OKN4395 as monotherapy for the remainder of treatment.

Group VIII: Monotherapy Dose Escalation Phase (Phase 1a) Experimental Treatment 1 Intervention

The Monotherapy Escalation Phase will include increasing doses of OKN4395 alone in patients with solid tumors with a COX2-associated immunosuppressive pathway.

Group IX: Combination Dose Confirmation Phase (Phase 1a) Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

Epkin

Lead Sponsor

Trials

1

Recruited

170+

Precision For Medicine

Industry Sponsor

Trials

6

Recruited

640+

Published Research Related to This Trial

In a phase Ib trial involving 26 patients with advanced PD-L1-positive ovarian cancer, pembrolizumab demonstrated a confirmed objective response rate of 11.5%, indicating some level of antitumor activity, with 1 complete response and 2 partial responses observed.

The treatment was generally well-tolerated, with 73.1% of patients experiencing treatment-related adverse events, but no deaths or treatment discontinuations due to these events, suggesting that pembrolizumab has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. Varga, A., Piha-Paul, S., Ott, PA., et al.[2019]

Pembrolizumab combined with adjuvant chemotherapy significantly improves one-year survival rates, overall response rates, and progression-free survival in patients with advanced non-small cell lung cancer (NSCLC), based on a meta-analysis of 14 studies.

This treatment not only enhances efficacy but also reduces the incidence of adverse drug reactions, indicating a favorable safety profile, although further validation through larger randomized controlled trials is needed.

NCBI (Pubmed)

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. Guo, WW., Zhang, TW., Wang, BL., et al.[2023]

In a real-life study of 108 patients with advanced non-small cell lung cancer (NSCLC) and a PD-L1 tumor proportion score of ≥50%, pembrolizumab showed a median progression-free survival of 10.1 months, similar to results from the KEYNOTE-024 trial.

The treatment was generally well-tolerated, with only 8% of patients experiencing grade 3 adverse events, and no severe (grade 4 or 5) adverse events reported, indicating a favorable safety profile.

NCBI (Pubmed)

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. Amrane, K., Geier, M., Corre, R., et al.[2021]

In a study involving 173 patients with advanced melanoma who had not responded to previous treatments, pembrolizumab showed an overall response rate of 26% at both 2 mg/kg and 10 mg/kg doses, indicating its potential effectiveness in this challenging patient population.

The treatment was well tolerated with no drug-related deaths, and the safety profiles were similar across both doses, with fatigue, pruritus, and rash being the most common side effects.

NCBI (Pubmed)

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. Robert, C., Ribas, A., Wolchok, JD., et al.[2022]

A systematic review of four trials involving 3425 patients found that lower doses of pembrolizumab (2 mg/kg every 3 weeks) are equally effective as higher doses (10 mg/kg) in treating advanced melanoma and non-small-cell lung cancer (NSCLC).

The safety profile of pembrolizumab was similar across different doses, suggesting that the lower dose may be sufficient for routine treatment without compromising efficacy.

NCBI (Pubmed)

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. Abdel-Rahman, O.[2018]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

In a study of 1,026 treatment-naïve patients with metastatic non-small-cell lung cancer (NSCLC) and PD-L1 expression of ≥50%, pembrolizumab showed an objective response rate of 44.5%, with median progression-free survival of 7.9 months and overall survival of 17.2 months.

Higher PD-L1 expression (≥90%) was linked to better treatment outcomes, while factors like poor performance status and the presence of bone or liver metastases were associated with worse clinical outcomes, indicating the importance of patient selection for pembrolizumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50. Cortellini, A., Tiseo, M., Banna, GL., et al.[2020]

Pembrolizumab is an effective monoclonal antibody that targets the PD-1 immune checkpoint, helping to restore T cell anti-tumor responses, and is administered at a dose of 200 mg every 3 weeks until disease progression or for up to 24 months.

It has received approval for treating various cancers, including melanomas and non-small cell lung cancers, particularly in tumors that are hypermutated or express PD-L1, but ongoing research aims to expand its use to less immunogenic tumor types through combination therapies.

NCBI (Pubmed)

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. du Rusquec, P., de Calbiac, O., Robert, M., et al.[2023]

In a phase 2 trial involving 12 patients with advanced osteosarcoma, pembrolizumab showed no clinical benefit at 18 weeks, with all patients experiencing disease progression and a median overall survival of only 6.6 months.

Despite the lack of significant antitumor activity, pembrolizumab was well-tolerated, with no treatment-related deaths or severe adverse events, suggesting it may be safe for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial. Boye, K., Longhi, A., Guren, T., et al.[2022]

In a study of 655 patients with advanced melanoma, pembrolizumab showed an overall objective response rate of 33%, indicating its efficacy in treating this type of cancer.

The median overall survival for patients receiving pembrolizumab was 23 months, with a 12-month survival rate of 66%, while 14% of patients experienced severe treatment-related adverse events, highlighting its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Pembrolizumab With Tumor Response and Survival Among Patients With Advanced Melanoma. Ribas, A., Hamid, O., Daud, A., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06789172

Study Details | NCT06789172 | A Phase 1, First-in-human ... The Monotherapy Escalation Phase will include increasing doses of OKN4395 alone in patients with solid tumors with a COX2-associated immunosuppressive pathway.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS2683

INVOKE: A phase 1 study of OKN4395, a first-in-class EP2 ... OKN4395 is hypothesized to modulate the tumor microenvironment to allow an effective immune response as monotherapy, and to potentiate the ...

3. jitc.bmj.com jitc.bmj.com/content/13/Suppl_2/A1334

1169 OKN4395: a first-in-class highly potent and selective ... Conclusions Our studies demonstrate that triple inhibition of EP2, EP4, and DP1 with OKN4395 is more effective than dual EP2/EP4 inhibition in ...

4. withpower.com withpower.com/trial/okn4395-pembrolizumab-for-solid-tumors-407b8

OKN4395 + Pembrolizumab for Solid Tumors (INVOKE Trial) A systematic review of four trials involving 3425 patients found that lower doses of pembrolizumab (2 mg/kg every 3 weeks) are equally effective as higher doses ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06789172/a-phase-1-first-in-human-study-of-okn4395-and-pembrolizumab-in-patients-with-solid-tumors

A Phase 1, First-in-human Study of OKN4395 and ... The purpose of this study is to investigate the study drug, OKN4395, administered alone and in combination with pembrolizumab.

6. owkin.com owkin.com/newsfeed/owkin-announces-first-patient-dosed-in-phase-1-clinical-trial-of-okn4395

Owkin announces first patient dosed in Phase 1 Clinical ... OKN4395 is the first compound in the clinic to selectively inhibit EP2, EP4, and DP1 receptors. This novel mechanism offers the potential to restore immune ...