Lenvatinib + Pembrolizumab for Uveal Melanoma

Overseen By Chris Fountain, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Providence Health & Services

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Pregnancy, Active infection, CNS metastases, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 104 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining lenvatinib, a cancer treatment drug, and pembrolizumab, an immunotherapy drug, for treating metastatic uveal melanoma, a type of eye cancer that has spread. Participants will receive both medications to determine if they can slow the cancer's progression. Eligible participants must have a confirmed diagnosis of metastatic uveal melanoma and measurable disease. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy or certain steroids, you may need to stop them before starting the trial. 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 lenvatinib and pembrolizumab is being tested for safety in treating advanced uveal melanoma, a type of eye cancer. Earlier studies have shown encouraging results. Many patients tolerated the combination well, though some experienced side effects, which were usually manageable.

In one study, patients with uveal melanoma had a 31.8% rate of living without the cancer worsening in one group and a 60.7% rate in another group. This suggests the treatment can work for some people, but individual experiences may differ.

Prospective trial participants should understand the possible side effects and discuss them with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for uveal melanoma?

Researchers are excited about the combination of Lenvatinib and Pembrolizumab for uveal melanoma because this treatment targets the cancer in a novel way. Unlike traditional therapies that may focus solely on destroying cancer cells, Lenvatinib is a targeted therapy that hinders the cancer's ability to form new blood vessels, effectively starving the tumor. Meanwhile, Pembrolizumab is an immunotherapy that activates the body's immune system to recognize and attack cancer cells more effectively. By combining these two approaches, there's potential for a more comprehensive assault on the cancer, offering hope for better outcomes compared to existing treatments.

What evidence suggests that lenvatinib and pembrolizumab might be an effective treatment for metastatic uveal melanoma?

Research has shown that combining lenvatinib and pembrolizumab yields promising results for treating metastatic uveal melanoma. In some patient groups, this combination delayed cancer progression in 31.8% to 60.7% of cases, indicating a slowdown in the disease's advancement for many patients. Additionally, the treatment stabilized the disease in numerous cases, with 12.5% of patients experiencing a reduction in cancer and 70.8% maintaining disease control. Although side effects occurred, with some patients experiencing severe reactions, evidence suggests this combination can effectively manage the disease. ^{2 3 5 6 7}

Who Is on the Research Team?

Matthew Taylor, MD

Principal Investigator

Providence Health & Services

Are You a Good Fit for This Trial?

This trial is for adults with a confirmed diagnosis of metastatic uveal melanoma who haven't been treated with certain immune therapies before. Participants must have measurable disease, provide tissue samples, and have good organ function and performance status. They should agree to use contraception and not be pregnant or breastfeeding.

Inclusion Criteria

The participant (or legally acceptable representative if applicable) provides written informed consent for the trial

I have provided a sample of my tumor that has not been treated with radiation.

I am fully active or can carry out light work.

Exclusion Criteria

You have uncorrected problems with the minerals in your body.

I have no health issues that could affect the study's results.

You have high levels of protein in your urine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Lenvatinib 20 mg daily and Pembrolizumab 200 mg IV every 3 weeks for up to 2 years

Up to 104 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Safety Monitoring

Evaluate the safety and tolerability of treatment with lenvatinib plus pembrolizumab

30 days

What Are the Treatments Tested in This Trial?

Interventions

• Lenvatinib
• Pembrolizumab

Trial Overview The study tests the effectiveness of combining lenvatinib with pembrolizumab in treating metastatic uveal melanoma. It aims to see how well these drugs work together for patients who haven't received similar treatments previously.

How Is the Trial Designed?

Group I: Pembrolizumab + Lenvatinib Experimental Treatment 2 Interventions

Lenvatinib 20 mg daily plus pembrolizumab 200 mg IV every 3 weeks.

Lenvatinib is already approved in United States, European Union for the following indications:

Approved in United States as Lenvima for:

• Differentiated Thyroid Cancer
• Renal Cell Carcinoma
• Hepatocellular Carcinoma
• Endometrial Cancer

Approved in European Union as Lenvima for:

• Thyroid Cancer
• Renal Cell Carcinoma
• Hepatocellular Carcinoma
• Endometrial Cancer

Approved in European Union as Kisplyx for:

• Renal Cell Carcinoma

Who Is Running the Clinical Trial?

Providence Health & Services

Lead Sponsor

Trials

131

Recruited

827,000+

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

Eisai Inc.

Industry 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

The combination of lenvatinib and pembrolizumab shows significant clinical benefits for patients with endometrial carcinoma, with a safety profile consistent with each drug's individual use, primarily involving manageable side effects like hypertension and hypothyroidism.

Effective management of lenvatinib's common adverse events is crucial to maximize its efficacy, as most side effects can be prevented or mitigated through proactive monitoring and intervention during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma. Lorusso, D., Danesi, R., Locati, LD., et al.[2023]

In a phase 3 trial with 1069 patients, the combination of lenvatinib and pembrolizumab significantly improved progression-free survival compared to sunitinib, with a median of 23.9 months versus 9.2 months, indicating a strong efficacy of this regimen.

Lenvatinib plus pembrolizumab also resulted in longer overall survival compared to sunitinib, while the combination of lenvatinib and everolimus did not show a survival advantage over sunitinib. However, both lenvatinib combinations had a high incidence of grade 3 or higher adverse events, similar to sunitinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. Motzer, R., Alekseev, B., Rha, SY., et al.[2022]

Uveal melanoma, the most common eye cancer in adults, has a significant risk of metastasis, with up to 50% of patients developing metastases within 15 years after treatment of the primary tumor.

Current systemic therapies for uveal melanoma have limited efficacy, but ongoing research is exploring new candidate drugs, including bortezomib and MEK inhibitors, to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New therapeutic agents in uveal melanoma. Velho, TR., Kapiteijn, E., Jager, MJ.[2012]

In a study of 64 patients with metastatic uveal melanoma treated with a combination of CTLA-4 and PD-1 inhibitors, the overall response rate was 15.6%, with a median overall survival of 16.1 months, indicating that this combination therapy may be the most effective option currently available for this difficult-to-treat cancer.

Despite a significant number of patients experiencing severe treatment-related adverse events (39.1%), the tolerability of this combined therapy appears to be better than that seen in trials for cutaneous melanoma, suggesting a potentially safer profile for patients with uveal melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined immune checkpoint blockade for metastatic uveal melanoma: a retrospective, multi-center study. Heppt, MV., Amaral, T., Kähler, KC., et al.[2023]

In a phase 1b study involving 6 Japanese patients with metastatic solid tumors, the combination of lenvatinib and pembrolizumab was well-tolerated, with no dose-limiting toxicities reported.

The treatment showed promising antitumor activity, with an objective response rate of 33.3%, particularly in patients with urothelial cancer, indicating potential efficacy for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A feasibility study of lenvatinib plus pembrolizumab in Japanese patients with advanced solid tumors. Kitano, S., Fujiwara, Y., Shimizu, T., et al.[2022]

In a phase 2 study involving 38 patients with pleural mesothelioma, the combination of pembrolizumab and lenvatinib resulted in a promising objective response rate of 58%, indicating significant anti-tumor activity after prior chemotherapy.

However, the treatment was associated with considerable toxicity, with 26% of patients experiencing serious treatment-related adverse events, including one death, highlighting the need for careful monitoring and supportive care during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus lenvatinib in second-line and third-line patients with pleural mesothelioma (PEMMELA): a single-arm phase 2 study. Douma, LH., Lalezari, F., van der Noort, V., et al.[2023]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

In the phase II LEAP-004 study involving 103 patients with advanced melanoma who had disease progression on PD-1 inhibitors, the combination of lenvatinib and pembrolizumab achieved an objective response rate of 21.4%, indicating its potential effectiveness in this challenging population.

The treatment demonstrated a median progression-free survival of 4.2 months and an overall survival of 14.0 months, with a manageable safety profile, including a 45.6% incidence of grade 3-5 adverse events, primarily hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II LEAP-004 Study of Lenvatinib Plus Pembrolizumab for Melanoma With Confirmed Progression on a Programmed Cell Death Protein-1 or Programmed Death Ligand 1 Inhibitor Given as Monotherapy or in Combination. Arance, A., de la Cruz-Merino, L., Petrella, TM., et al.[2023]

Combination therapy with pembrolizumab and lenvatinib is effective as a first-line treatment for clear cell renal carcinoma and as a second-line option for recurrent or metastatic endometrial carcinoma, based on data from five completed clinical trials and two ongoing trials.

This non-chemotherapy regimen helps spare patients from prolonged myelosuppression and lowers the risk of infection, making it a safer alternative for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined use of pembrolizumab and lenvatinib: A review. Eisinger, C., Muluneh, B.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11491429/

pembrolizumab and lenvatinib versus conventional ... Grade 3–5 treatment-related adverse events were documented in 48.7% (pembrolizumab/lenvatinib) and 75.6% (CC) of patients (p=0.034), which led ...

2. esmoopen.com esmoopen.com/article/S2059-7029(25)01283-9/fulltext

65eP Real-world impact of pembrolizumab plus lenvatinib ... The ORR was 12.5% (3 PR), and the disease control rate (DCR) was 70.8%. mPFS was 6.8 mon (95% CI 2.6–14.9). mOS from the start of therapy was 9.5 mon (95% CI ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00928-7/fulltext

Randomized, double-blind, phase III LEAP-003 study of ... Grade 3-5 treatment-related AEs occurred in 58.7% with lenvatinib + pembrolizumab versus 29.0% with placebo + pembrolizumab. •. Lenvatinib + ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05282901

NCT05282901 | Efficacy and Safety of Pembrolizumab in ... Taken together, we hypothesize that combining pembrolizumab with lenvatinib in metastatic UM may target essential cellular oncogenic pathways while normalizing ...

5. targetedonc.com targetedonc.com/view/pembrolizumab-plus-lenvatinib-shows-encouraging-efficacy-in-uveal-melanoma

Pembrolizumab Plus Lenvatinib Shows Encouraging ... Pembrolizumab and lenvatinib showed promising PFS in uveal melanoma patients, with 31.8% and 60.7% rates in different cohorts. The safety ...

6. merck.com merck.com/news/merck-and-eisai-provide-update-on-phase-3-leap-012-trial-in-unresectable-non-metastatic-hepatocellular-carcinoma/

Merck and Eisai Provide Update on Phase 3 LEAP-012 ... The five-year relative survival rate for liver cancer in the U.S. is 22% based on Surveillance, Epidemiology, and End Results (SEER) data from ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS9613

PLUME: A single-arm phase II trial evaluating ... A single-arm phase II trial evaluating the combination of pembrolizumab and lenvatinib in metastatic uveal melanoma (mUM) patients.