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

26 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination of Lenvatinib and Pembrolizumab for skin cancer?

Research shows that the combination of Lenvatinib and Pembrolizumab has been effective in treating melanoma, a type of skin cancer, especially in cases where other treatments have failed. This combination has also shown promise in other cancers, suggesting it could be a powerful option for skin cancer treatment. ^{1 2 3 4 5}

Is the combination of Lenvatinib and Pembrolizumab safe for humans?

The combination of Lenvatinib and Pembrolizumab has been studied for safety in various cancers, showing some common adverse reactions (side effects) like those seen in renal cell carcinoma. However, there have been reports of serious side effects, such as toxic epidermal necrolysis (a severe skin reaction), in rare cases. ^{2 4 6 7 8}

How is the drug combination of lenvatinib and pembrolizumab unique for treating skin cancer?

The combination of lenvatinib and pembrolizumab is unique because it targets melanoma that has progressed despite previous treatments with PD-1 or PD-L1 inhibitors. Lenvatinib is a multikinase inhibitor that blocks signals that help cancer cells grow, while pembrolizumab is an immune checkpoint inhibitor that helps the immune system attack cancer cells. ^{1 2 4 5 9}

What is the purpose of this trial?

This is a single arm trial of participants with Merkel cell carcinoma receiving a combination of lenvatinib plus pembrolizumab.

Research Team

Andrew Brohl, MD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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 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]

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 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]

References

1. United States 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. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and efficacy of pembrolizumab plus lenvatinib versus pembrolizumab and lenvatinib monotherapies in cancers: A systematic review. [2021]

3. Switzerland 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Combined use of pembrolizumab and lenvatinib: A review. [2023]

5. England 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. [2023]

6. England 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. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Combination therapy (toripalimab and lenvatinib)-associated toxic epidermal necrolysis in a patient with metastatic liver cancer: A case report. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Adverse events and oncologic outcomes with combination lenvatinib and pembrolizumab for the treatment of recurrent endometrial cancer. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. [2022]