E7386 + Pembrolizumab for Solid Cancers

No longer recruiting at 50 trial locations

Overseen By Eisai Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Eisai Inc.

Must be taking: Vitamin D

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: CNS metastases, Active infection, Autoimmune, others

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

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new drug combination for individuals with certain advanced solid tumors, such as melanoma, colorectal cancer (CRC), and hepatocellular carcinoma (HCC). The main focus is to evaluate how well the drugs E7386 (an experimental treatment) and pembrolizumab work together, with lenvatinib added for some HCC cases. The trial seeks participants whose previous treatments failed and who have measurable tumors. It may suit those with advanced melanoma, CRC, or HCC who have experienced disease progression after prior treatments. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer research.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants should not have changes in antihypertensive medications within 1 week before starting treatment. It's best to discuss your specific medications with the trial team.

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

Research shows that the combination of E7386 and pembrolizumab is generally safe. Earlier studies found that participants handled this combination well without major problems. The main goal was to determine the effective dose with minimal side effects. For the combination of E7386, pembrolizumab, and lenvatinib, studies found a similar safety level. Patients usually managed the treatment well, with some experiencing expected and manageable side effects. These results suggest a good safety record, but individual experiences can differ. Always consult a healthcare provider about potential risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine E7386 and pembrolizumab, with one arm also adding lenvatinib, offering a new approach to tackling solid cancers. Unlike standard treatments, which often rely on traditional chemotherapy or single-agent immunotherapy, these combinations could enhance the immune system's ability to fight cancer more effectively. E7386 is particularly intriguing as it targets the Wnt/β-catenin signaling pathway, which is crucial in cancer progression and is not typically addressed by existing therapies. By potentially overcoming resistance mechanisms and enhancing immune response, these treatments aim to improve outcomes where current options may fall short.

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

Research shows that pembrolizumab helps treat various solid cancers, such as melanoma and non-small cell lung cancer, by increasing survival rates. In this trial, participants will receive either the combination of E7386 and pembrolizumab or the combination of E7386, pembrolizumab, and lenvatinib. Studies have tested the safety and effectiveness of combining E7386 with pembrolizumab for conditions like colorectal cancer and melanoma. Early results suggest this combination is generally safe and may enhance cancer-fighting effects.

For the combination of E7386, pembrolizumab, and lenvatinib, trial data indicate it could be promising for treating advanced cancers. Specifically, this combination has shown significant survival benefits for patients with certain cancers over five years. These studies provide strong evidence for the potential effectiveness of these treatments in targeting hard-to-treat solid tumors. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced solid tumors (melanoma, colorectal cancer, or hepatocellular carcinoma) that have progressed despite previous treatments. Participants must be in good physical condition and have at least one measurable tumor. Specific criteria apply to each type of cancer regarding prior therapies and disease stage.

Inclusion Criteria

I have colorectal cancer and have had 2-4 treatments for it, but they didn't work or I couldn't tolerate them.

My cancer has worsened despite treatment.

I have a tumor that can be measured by CT or MRI.

Exclusion Criteria

I am currently being treated for an infection.

I stopped a cancer treatment due to severe side effects.

My brain metastases are stable, and I haven't needed steroids for 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1b Treatment

Participants receive E7386 in combination with pembrolizumab to assess safety and tolerability and determine the recommended Phase 2 dose (RP2D)

21 days per cycle, until RP2D is determined

Visits every 3 weeks

Phase 2 Treatment

Participants receive E7386 in combination with pembrolizumab (and lenvatinib for HCC) to assess the objective response rate (ORR)

21 days per cycle, up to approximately 3 years 11 months

Visits every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• E7386
• Lenvatinib
• Pembrolizumab

Trial Overview The study tests E7386 combined with pembrolizumab for safety, tolerability, and the optimal dose in Phase 1b. In Phase 2, it evaluates how well this combination works on melanoma, colorectal cancer, and hepatocellular carcinoma; plus lenvatinib is added for some liver cancer patients.

How Is the Trial Designed?

Group I: Phase 2: E7386 + Pembrolizumab + Lenvatinib Experimental Treatment 3 Interventions

Participants will be randomized to receive E7386 Dose 1 (Cohort 1) or Dose 2 (Cohort 2) tablet, BID, orally in combination with pembrolizumab 200 mg Q3W IV infusion plus lenvatinib 8 mg capsule, orally, once daily (QD) continuously in 21-days treatment cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the study. The dose of treatment depends on tolerability data of both Cohorts.

Group II: Phase 1b and 2: E7386 + Pembrolizumab Experimental Treatment 2 Interventions

Participants will receive E7386 twice daily (BID) along with pembrolizumab 200 mg intravenous (IV) infusion once every 3 weeks (Q3W) in 21-day treatment cycle until RP2D is determined in Phase 1b. The recommended dose for Phase 2 part of the study will be based on Phase 1b result. Participants will continue to receive study treatment in Phase 2 part until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the study.

Who Is Running the Clinical Trial?

Eisai Inc.

Lead Sponsor

Trials

524

Recruited

161,000+

Founded

Eisai Inc. was established in 1995 as the U.S. subsidiary of Eisai Co., Ltd.

Headquarters

Woodcliff Lake, NJ, USA

Known For

Neurology and Oncology

Top Products

Aricept (donepezil), Lenvima (lenvatinib), Leqembi (lecanemab), Halaven (eribulin)

Lynn Kramer

Eisai Inc.

Chief Medical Officer since 2019

MD

Tatsuyuki Yasuno

Eisai Inc.

Chief Executive Officer since 2023

MBA from Kellogg School of Management, Northwestern University; Bachelor of Political Science from Waseda University

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Nivolumab and pembrolizumab are FDA-approved monoclonal antibodies that target PD-1, helping to enhance T cell activity against cancer by blocking the PD-1/PD-L1 interaction, which allows cancer cells to escape immune detection.

Both drugs have shown efficacy across multiple cancer types, including melanoma and non-small cell lung cancer, and are considered interchangeable options for treating these conditions, which may help manage the rising costs of cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Prasad, V., Kaestner, V.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05091346

NCT05091346 | A Study of E7386 in Combination With ... This study is conducted to assess the safety and tolerability of E7386 in combination with pembrolizumab in participants with previously treated selected solid ...

2. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2025.43.16_suppl.5599

E7386 study 102: Global dose-expansion cohort of ... E7386 + LEN showed promising antitumor activity with a manageable safety profile in heavily pretreated pts with aEC following platinum-based chemo and IO.

3. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X25009314

Clinical Trials Randomized study evaluating optimal dose ... E7386 plus lenvatinib will show a manageable safety profile and clinically meaningful anti-tumor activity in patients with advanced, un-resectable, or ...

4. withpower.com withpower.com/trial/phase-2-melanoma-9-2021-a2982

E7386 + Pembrolizumab for Solid Cancers Pembrolizumab has shown effectiveness in treating various solid tumors, including non-small cell lung cancer and melanoma, by improving survival rates and ...

5. clinicaltrials.eu clinicaltrials.eu/trial/study-of-e7386-and-pembrolizumab-for-patients-with-previously-treated-colorectal-cancer-melanoma-or-hepatocellular-carcinoma/

Study of E7386 and Pembrolizumab for Patients with ... This study tests the safety and efficacy of E7386 and Pembrolizumab combination treatment in patients with previously treated colorectal ...

6. data.niaid.nih.gov data.niaid.nih.gov/resources?id=2393260

A Study of E7386 in Combination With Pembrolizumab ... The Phase 1b part of this study is conducted to assess the safety and tolerability of E7386 in combination with pembrolizumab in participants with ...

7. trial.medpath.com trial.medpath.com/clinical-trial/ab286d6f0a3619fd

A Study of E7386 in Combination With Pembrolizumab in ... The Phase 1b part of this study is conducted to assess the safety and tolerability of E7386 in combination with pembrolizumab in participants with ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS5632

Randomized study evaluating optimal dose, efficacy and ... E7386 + lenvatinib has demonstrated manageable safety and promising antitumor activity in the dose-expansion cohort of Study 102 that included ...