Lenvatinib + Pembrolizumab for Skin Cancer

Overseen By Marjorie Colon Colon

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Anti-PD-1, Anti-VEGFR

Disqualifiers: Uncontrolled hypertension, Cardiovascular impairment, Active infection, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, lenvatinib (a targeted therapy) and pembrolizumab (an immunotherapy), for individuals with Merkel cell carcinoma, a rare skin cancer. The goal is to evaluate how well these medications work together before surgery and whether pembrolizumab alone can help after surgery. This trial may suit those with surgically removable Merkel cell carcinoma who haven't previously used similar therapies. Participants should also be willing to monitor their blood pressure at home. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on certain treatments like systemic anti-cancer therapy, immunosuppressive therapy, or have received a live vaccine recently, you may need to stop or adjust those. 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 has shown that the combination of lenvatinib and pembrolizumab has been tested in people before. In these studies, 68% of participants experienced side effects, which were generally manageable. Importantly, no unexpected safety issues emerged. This indicates that while side effects are common, they are usually not severe or surprising. This trial further tests this combination to assess how well people handle it over time. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of lenvatinib and pembrolizumab for treating Merkel cell carcinoma because of its innovative approach. Unlike standard treatments that often rely solely on surgery, radiation, or chemotherapy, this treatment leverages pembrolizumab, an immunotherapy drug that boosts the body's immune system to fight cancer cells. Lenvatinib, a targeted therapy, inhibits proteins that promote cancer cell growth. Together, these drugs not only aim to shrink tumors before surgical removal but also continue attacking cancer cells post-surgery, potentially leading to more comprehensive and sustained cancer control.

What evidence suggests that lenvatinib plus pembrolizumab might be an effective treatment for skin cancer?

In this trial, participants with Merkel cell carcinoma will receive a combination of lenvatinib and pembrolizumab. Previous studies have shown promising results for this combination in treating Merkel cell carcinoma, a type of skin cancer. Specifically, research indicates that when used before surgery, this combination completely eliminated detectable cancer cells in about 58% of patients, suggesting its effectiveness in shrinking tumors. Additionally, this treatment combination significantly improved overall survival and extended the time patients live without disease progression. Studies have also demonstrated positive outcomes in patients who responded to this first-line immunotherapy. These findings suggest that the combination of lenvatinib and pembrolizumab could be a powerful option for patients with this type of skin cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Andrew Brohl, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

Adults diagnosed with Merkel cell carcinoma, stages II-IV, who can provide a tumor sample and are able to monitor their blood pressure at home. They must not be pregnant or breastfeeding and agree to use contraception. Excluded are those with active autoimmune diseases, certain infections like HIV or hepatitis, severe allergies to trial drugs, recent other cancer treatments or vaccinations, uncontrolled high blood pressure, or any condition that could affect study results.

Inclusion Criteria

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

My organs are functioning well.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study

I have had pneumonitis treated with steroids or currently have it.

I have active brain metastases or cancer in the lining of my brain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive two cycles (6 weeks) of lenvatinib plus pembrolizumab

6 weeks

Surgical Resection

Participants undergo planned surgical resection within 2-4 weeks following completion of cycle 2

2-4 weeks

Adjuvant Therapy

Following surgical recovery, participants may receive adjuvant radiation therapy if indicated

Pembrolizumab Monotherapy

Participants resume treatment with pembrolizumab monotherapy to complete 17 cycles total

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Lenvatinib
• Pembrolizumab

Trial Overview The trial is testing the combination of two drugs: Lenvatinib (oral) and Pembrolizumab (injection), in patients with Merkel cell carcinoma. It's a single-arm study where all participants receive the same treatment regimen before surgery to remove detectable cancer.

How Is the Trial Designed?

Group I: Lenvatinib plus Pembrolizumab Experimental Treatment 2 Interventions

Participants with Merkel cell carcinoma amenable to complete resection will receive two cycles (6 weeks) of therapy with the combination of lenvatinib plus pembrolizumab and then proceed to planned resection within 2-4 weeks following completion of cycle 2. Following surgical recovery and completion of adjuvant radiation therapy (if indicated), treatment will resume with pembrolizumab monotherapy with intent to complete 17 cycles total of pembrolizumab.

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

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

Published Research Related to This Trial

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]

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]

In a study of 43 patients with recurrent endometrial cancer treated with lenvatinib and pembrolizumab, 84% experienced significant adverse events (AEs), with hypertension and weight loss being the most common.

Patients starting on a reduced dose of lenvatinib (10 mg or 14 mg) had significantly longer progression-free survival compared to those on the standard dose (20 mg), suggesting that dose optimization may improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events and oncologic outcomes with combination lenvatinib and pembrolizumab for the treatment of recurrent endometrial cancer. Zammarrelli, WA., Ma, W., Espino, K., et al.[2023]

In the CLEAR study involving 352 patients, the combination of lenvatinib and pembrolizumab showed a manageable safety profile, with common adverse reactions including fatigue (63.1%), diarrhea (61.9%), and hypertension (56.3%).

Most adverse reactions occurred within approximately 5 months of starting treatment, and effective management strategies such as monitoring and dose modifications were identified to ensure patient safety and support ongoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization and Management of Adverse Reactions From the CLEAR Study in Advanced Renal Cell Carcinoma Treated With Lenvatinib Plus Pembrolizumab. Motzer, R., George, S., Merchan, JR., et al.[2023]

The combination of pembrolizumab and lenvatinib demonstrated significantly higher objective response rates (ORRs) and progression-free survival (mPFS) compared to their individual therapies in solid cancers, with ORRs reaching up to 70% in renal cell carcinoma.

Despite a high incidence of adverse events (68.0% for the combination therapy), the toxicities were manageable and no unexpected safety issues were reported, indicating that the combination therapy is both effective and relatively safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of pembrolizumab plus lenvatinib versus pembrolizumab and lenvatinib monotherapies in cancers: A systematic review. Mo, DC., Luo, PH., Huang, SX., et al.[2021]

In a phase 3 study involving 487 patients with advanced urothelial carcinoma, the combination of pembrolizumab and lenvatinib did not show improved progression-free survival (4.5 months) or overall survival (11.8 months) compared to pembrolizumab with placebo.

The combination treatment resulted in a higher rate of severe adverse events (51%) compared to the placebo group (27%), leading to the conclusion that the benefit-to-risk ratio was not favorable for using lenvatinib with pembrolizumab as first-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab with or Without Lenvatinib as First-line Therapy for Patients with Advanced Urothelial Carcinoma (LEAP-011): A Phase 3, Randomized, Double-Blind Trial. Matsubara, N., de Wit, R., Balar, AV., et al.[2023]

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. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.9514

A phase II study of neoadjuvant lenvatinib plus ... Lenvatinib plus pembrolizumab demonstrated encouraging efficacy with anticipated toxicity when used as neoadjuvant therapy for Merkel cell carcinoma.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11260505/

The Evolving Treatment Landscape of Merkel Cell ... Neoadjuvant Lenvatinib Plus Pembrolizumab in Merkel Cell Carcinoma ... outcomes in advanced Merkel cell carcinoma patients responding to first-line immunotherapy.

3. merck.com merck.com/news/keytruda-pembrolizumab-plus-lenvima-lenvatinib-combination-demonstrated-statistically-significant-improvement-in-overall-survival-progression-free-survival-and-objective-response-rate/

KEYTRUDA® (pembrolizumab) Plus LENVIMA® ... KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC) ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04869137

Neoadjuvant Lenvatinib Plus Pembrolizumab in Merkel ... Study Overview. Brief Summary. This is a single arm trial of participants with Merkel cell carcinoma receiving a combination of lenvatinib plus pembrolizumab.

5. x.com x.com/MoffittNews/status/1929568320279486544

"Immunotherapy Combo Shows Promise as ... A combination of pembrolizumab and lenvatinib used before surgery led to the complete elimination of detectable cancer cells in nearly 58% of patients with ...

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8495203/

Merkel Cell Carcinoma: An Immunotherapy Fairy-Tale? - PMC In the PD-L1-positive and PD-L1-negative subgroups, 1-y OS rates were 71% and 56%, respectively. The SPEAR-Merkel study has been published in 2021 and reported ...

8. withpower.com withpower.com/trial/phase-3-carcinoma-4-2021-8cac5

Lenvatinib + Pembrolizumab for Skin Cancer Despite a high incidence of adverse events (68.0% for the combination therapy), the toxicities were manageable and no unexpected safety issues were reported, ...