E7386 + Lenvatinib for Solid Cancer

Recruiting at 147 trial locations

Overseen By Eisai Inquiry Service

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Eisai Inc.

Must not be taking: Antiretrovirals, Antiplatelets

Disqualifiers: HIV, Cardiac conditions, Active infection, others

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

Compensation: Varies

Number of Visits: Unknown

301 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to determine the optimal dose and assess the safety of a new cancer treatment called E7386, used alone or with lenvatinib. It targets individuals with endometrial cancer, liver cancer, and other solid tumors unresponsive to previous treatments. This trial suits those with a confirmed diagnosis of these cancers who have not found success with other treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial requires an adequate washout period (time without taking certain medications) before starting the study drugs. This includes stopping chemotherapy and radiotherapy for 3 weeks or more, and any antitumor therapy with antibodies for 4 weeks or more. You should discuss your specific medications with the study team to see if they need to be stopped.

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

Research has shown that combining E7386 with lenvatinib has a manageable safety profile for patients with solid tumors. In one study involving 16 patients, early results indicated that side effects were generally tolerable. The goal is to determine the optimal dose that balances safety and effectiveness.

Prospective trial participants should note that lenvatinib has FDA approval for other uses, which may reassure regarding its safety when used alone. However, the combination with E7386 remains under study to ensure it is safe and well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about E7386 combined with lenvatinib for treating solid cancers because this combo targets cancer growth in a novel way. While traditional treatments like chemotherapy attack cancer cells broadly, E7386 works by inhibiting a specific pathway, the Wnt/β-catenin signaling pathway, that is crucial for cancer cell survival and proliferation. This targeted approach could potentially lead to fewer side effects than standard therapies. Additionally, lenvatinib enhances the anti-tumor effect by blocking proteins that help tumors form new blood vessels, effectively starving the cancer. This dual-action strategy offers a promising new avenue for more effective cancer treatment.

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

Research has shown that combining E7386 and lenvatinib yields promising results for treating certain solid tumors. In this trial, participants will receive different treatment regimens based on their specific cancer type, including E7386 with lenvatinib or lenvatinib alone. Studies have found this combination to be generally safe, with most patients tolerating the side effects. The treatment effectively reduces or controls tumors, particularly in hard-to-treat cases, by blocking a pathway involving proteins like β-catenin that aid tumor growth. These findings offer hope for improved outcomes in treating solid cancers. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with certain solid tumors like liver cancer, colorectal cancer, or endometrial cancer. They should have a specific stage of disease and no effective standard treatments left to try. Participants need to be relatively healthy otherwise, with good organ function and performance status. Those who've had recent major surgeries or active infections (except hepatitis B/C in liver cancer patients) can't join.

Inclusion Criteria

For HCC participants only: Child-Pugh score A

I haven't had blood transfusions or G-CSF treatments in the last 2 weeks and have recovered from any radiation side effects without needing steroids.

My blood pressure, kidney, liver, bone marrow functions, and mineral levels are all within normal ranges.

Exclusion Criteria

I am currently infected with COVID-19 or still recovering from its effects.

I do not have an active infection needing treatment, except for HBV/HCV if I have liver cancer.

My urine protein levels are below 1 gram per 24 hours.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive E7386 in combination with lenvatinib in 28-day treatment cycles to determine the recommended Phase 2 dose

28 days per cycle

Cycle 0: 6 or 7 days, followed by Cycle 1: 28 days

Dose Expansion

Participants receive E7386 in combination with lenvatinib or lenvatinib monotherapy in 28-day treatment cycles to assess safety and tolerability

28 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• E7386
• Lenvatinib

Trial Overview The study is testing the safety and best dose of E7386 when combined with another anticancer drug called Lenvatinib in people with various solid tumors. The goal is to find out what amount of E7386 can be given safely without causing too many side effects.

How Is the Trial Designed?

Group I: Dose Optimization Part: EC Participants Experimental Treatment 4 Interventions

Participants with EC will be randomized to receive 2 different doses of E7386 in combination with lenvatinib capsule or lenvatinib capsule monotherapy in 28-days cycles, or treatment of physician's choice (TPC; doxorubicin in 21-day cycles or paclitaxel in 28-day cycles \[3 weeks on/1 week off\]), until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program.

Group II: Dose Expansion Part: HCC Subpart: Lenvatinib Only Experimental Treatment 1 Intervention

Participants with HCC will receive lenvatinib 8 mg (participants with body weight of \<60 kg) or 12 mg (participants with body weight \>=60 kg), capsules, orally, QD in 28-day treatment cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program

Group III: Dose Expansion Part: HCC Subpart: E7386 + Lenvatinib Experimental Treatment 2 Interventions

Participants with HCC will receive lenvatinib 8 mg (participants with body weight of \<60 kg) or 12 mg (participants with body weight \>=60 kg), capsule, orally QD in combination with E7386 y, BID in 28-day treatment cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program.

Group IV: Dose Expansion Part: EC Subpart: E7386 + Lenvatinib Experimental Treatment 2 Interventions

Participants with endometrial cancer (EC) will receive E7386, BID in combination with lenvatinib 14 mg, capsules, orally, QD in 28-day treatment cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program.

Group V: Dose Expansion Part: CRC Subpart: E7386 + Lenvatinib Experimental Treatment 2 Interventions

Participants with colorectal cancer (CRC) will receive E7386, BID in combination with lenvatinib 20 mg, capsules, orally, QD in 28-day treatment cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program.

Group VI: Dose Escalation Part: Other ST: E7386 QD Subpart + Lenvatinib Experimental Treatment 2 Interventions

Participants with solid tumor (ST) (except for HCC) will receive E7386, QD for 5 or 6 consecutive days followed by a period of time without treatment in Cycle 0 (6 or 7 days). Participants with ST (except for HCC) will receive E7386, QD in combination with lenvatinib 20 mg, capsules, orally, QD in 28-day treatment cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program.

Group VII: Dose Escalation Part: Other ST: E7386 BID Subpart + Lenvatinib Experimental Treatment 2 Interventions

Participants with ST (except for HCC) will receive E7386, BID for 5 or 6 consecutive days in Cycle 0 (6 or 7 days). Participants with ST (except for HCC) will receive E7386, BID in combination with lenvatinib 20 mg, capsules, orally, QD in 28-day treatment cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program.

Group VIII: Dose Escalation Part: HCC: E7386 QD Subpart + Lenvatinib Experimental Treatment 2 Interventions

Participants with hepatocellular carcinoma (HCC) will receive E7386, once daily (QD) for 5 or 6 consecutive days followed by a period of time without treatment in Cycle 0 (6 or 7 days). Participants with HCC will receive E7386, QD in combination with lenvatinib 8 milligram (mg) (participants with body weight of less than \[\<\] 60 kilograms \[kg\]) or 12 mg (participants with body weight \>=60 kg), capsules, orally, QD in 28-day treatment cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program.

Group IX: Dose Escalation Part: HCC: E7386 BID Subpart + Lenvatinib Experimental Treatment 2 Interventions

Participants with HCC will receive E7386, twice daily (BID) for 5 or 6 consecutive days in Cycle 0 (6 or 7 days). Participants with HCC will receive E7386, BID in combination with lenvatinib 8 mg (participants with body weight of \< 60 kg) or 12 mg (participants with body weight \>=60 kg) capsules, orally, QD in 28-day treatment cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program.

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

Published Research Related to This Trial

Lenvatinib effectively inhibits the growth of liver cancer cells in vitro and in vivo, with its efficacy varying based on the expression levels of specific receptors (FGFR1-4, RET) in the cancer cells.

In animal models, lenvatinib reduced tumor growth by significantly decreasing blood vessel formation (angiogenesis) and increasing tumor necrosis, although it did not induce apoptosis in the cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiproliferative Effect of Lenvatinib on Human Liver Cancer Cell Lines In Vitro and In Vivo. Ogasawara, S., Mihara, Y., Kondo, R., et al.[2020]

Lenvatinib is an effective multikinase inhibitor approved for treating radioiodine-refractory differentiated thyroid cancer and advanced renal cell carcinoma, showing favorable efficacy in various malignancies.

While lenvatinib has beneficial effects, it is associated with common adverse events like hypertension and fatigue, necessitating careful monitoring and management to enhance patient quality of life and treatment adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing the adverse events associated with lenvatinib therapy in radioiodine-refractory differentiated thyroid cancer. Cabanillas, ME., Takahashi, S.[2019]

In a phase 1 study involving 27 patients, lenvatinib treatment led to significant tumor shrinkage, which correlated with changes in plasma angiogenic biomarkers such as increased VEGF and SDF1α levels and decreased sVEGFR2 levels.

Adverse events like hypertension and proteinuria were also linked to changes in these biomarkers, suggesting that monitoring plasma angiogenic proteins could help predict lenvatinib's efficacy and side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamic change in plasma angiogenic proteins: a dose-escalation phase 1 study of the multi-kinase inhibitor lenvatinib. Koyama, N., Saito, K., Nishioka, Y., et al.[2021]

Lenvatinib is an effective oral treatment for various cancers, including thyroid, liver, kidney, and endometrial cancers, and can be used alone or in combination with other therapies, based on extensive clinical trial data.

The dosing strategies for lenvatinib have been carefully established to maximize patient benefits while managing side effects, which are similar to those of other tyrosine kinase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib dose, efficacy, and safety in the treatment of multiple malignancies. Motzer, RJ., Taylor, MH., Evans, TRJ., et al.[2023]

The maximum tolerated dose (MTD) of lenvatinib when combined with carboplatin and paclitaxel for treating advanced non-small-cell lung cancer (NSCLC) is established at 4 mg taken twice daily, showing manageable side effects.

The treatment regimen resulted in a response rate of 68% and a median progression-free survival of 9.0 months, indicating promising antitumor activity in chemotherapy-naïve patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of lenvatinib combined with carboplatin and paclitaxel in patients with non-small-cell lung cancer. Nishio, M., Horai, T., Horiike, A., et al.[2021]

Lenvatinib (LEN) is an effective multikinase inhibitor used for treating certain types of cancer, but it often causes significant adverse events (AEs) like hypertension and diarrhea, which can lead to dose modifications or discontinuation of treatment.

A multidisciplinary approach to managing these AEs is crucial for maintaining treatment efficacy and patient safety, as it helps address the side effects that frequently arise during LEN therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib Long-Term Responses in Refractory Thyroid Cancer: Our Mono-Institutional Real-Life Experience with the Multidisciplinary Approach and Review of Literature. Denaro, N., Latina, A., Cesario, F., et al.[2019]

In a phase three study involving 392 patients with differentiated thyroid cancer, lenvatinib (24 mg/day) was associated with common adverse events such as diarrhea (67%), fatigue (67%), and proteinuria (32%), which typically occurred early and were manageable through dose modifications.

Overall survival was significantly linked to the occurrence of diarrhea, with patients experiencing diarrhea having a median overall survival that was not reached, compared to 17.1 months for those without diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and timing of common adverse events in Lenvatinib-treated patients from the SELECT trial and their association with survival outcomes. Haddad, RI., Schlumberger, M., Wirth, LJ., et al.[2019]

Lenvatinib, a multitargeted Tyrosine Kinase Inhibitor, has shown significant improvement in Progression-Free Survival (PFS) for patients with aggressive Differentiated Thyroid Cancer (DTC) not responsive to radioiodine, with a median PFS of 18.2 months compared to 3.6 months for placebo.

While lenvatinib is effective, it is associated with a high rate of adverse effects (over 40%), including hypertension and fatigue, and about 14% of patients may need to discontinue treatment due to these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib in the Therapy of Aggressive Thyroid Cancer: State of the Art and New Perspectives with Patents Recently Applied. Ferrari, SM., Ruffilli, I., Centanni, M., et al.[2018]

In a phase 2 study involving 46 patients with advanced hepatocellular carcinoma, lenvatinib demonstrated significant clinical activity with a median time to progression of 7.4 months and a median overall survival of 18.7 months.

The treatment was associated with manageable side effects, although 74% of patients required dose reductions due to adverse events, particularly in those with lower body weight, suggesting that body weight should be considered for dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma. Ikeda, K., Kudo, M., Kawazoe, S., et al.[2018]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.5599

Global dose-expansion cohort of E7386 + lenvatinib (LEN) ... E7386 is a novel oral anticancer agent that inhibits the interaction between β-catenin and CREB-binding protein. Study 102 evaluates E7386 + LEN ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40318924/

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

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04008797

NCT04008797 | A Study of E7386 in Combination With ... The primary objective of this study is to assess the safety and tolerability and to determine the recommended Phase 2 dose (RP2D) of E7386 in combination with ...

4. 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 ...

5. 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04008797

A Study of E7386 in Combination With Other Anticancer ... The primary objective of this study is to assess the safety and tolerability and to determine the recommended Phase 2 dose (RP2D) of E7386 in combination ...

7. jnccn.org jnccn.org/view/journals/jnccn/23/3.5/article-TIP25-243.xml

TIP25-243: Randomized Study Evaluating Optimal Dose ... E7386 + lenvatinib has demonstrated manageable safety and promising antitumor activity in the dose-expansion cohort of Study 102 that included patients with ...