Melanoma > Lenvatinib

Pembrolizumab + Lenvatinib for Skin and Kidney Cancers with Brain Metastases

Recruiting in Palo Alto (17 mi)

Overseen By Harriet Kluger, MD

Age: 18+

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Yale University

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This is a phase 2, Simon's 2-stage designed study with 2 cohorts of anti-PD-1/PD-L1 experienced patients with untreated brain metastases: 1) melanoma and 2) renal cell carcinoma (RCC).

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

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants should not have received anti-cancer therapy within 14 days before starting the trial and should not be on high doses of steroids or immunosuppressive therapy. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination of pembrolizumab and lenvatinib for treating skin and kidney cancers with brain metastases?

Research shows that the combination of pembrolizumab and lenvatinib has been effective in treating advanced gastric cancer, renal cell carcinoma, and urothelial carcinoma, suggesting potential benefits for other cancers as well. This combination has shown antitumor activity and is considered a standard treatment for certain types of kidney cancer.

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Is the combination of pembrolizumab and lenvatinib generally safe for humans?

The combination of pembrolizumab and lenvatinib has been studied in various cancers and has shown a manageable safety profile, meaning that while there are side effects, they can generally be managed with appropriate care.

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How is the drug combination of pembrolizumab and lenvatinib unique for treating skin and kidney cancers with brain metastases?

The combination of pembrolizumab and lenvatinib is unique because it pairs an immune checkpoint inhibitor (pembrolizumab) with a multikinase inhibitor (lenvatinib), which together enhance the body's immune response against tumors. This combination has shown promise in treating various cancers, including renal cell carcinoma, by improving anti-tumor activity compared to using either drug alone.

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Eligibility Criteria

Adults with melanoma or renal cell carcinoma (RCC) and untreated brain metastases who've had at least two doses of anti-PD-1/PD-L1 drugs. They must not be pregnant, agree to contraception, have a life expectancy over 3 months, stable blood pressure, good organ function, and an ECOG status of 0-1. Exclusions include symptomatic brain metastases, recent cancer treatments or vaccines, serious infections or bleeding risks.

Inclusion Criteria

I have received at least 2 doses of a drug targeting PD-1/PD-L1 in my treatment for melanoma or kidney cancer.

I am 18 or older with melanoma or kidney cancer that has spread to my brain and hasn't been treated.

I am not pregnant, not breastfeeding, and follow the contraceptive guidelines.

My cancer is confirmed as metastatic melanoma or kidney cancer.

I am fully active or can carry out light work.

Exclusion Criteria

I have symptoms from melanoma or kidney cancer that has spread to my brain.

I have had serious heart issues, like a heart attack or unstable angina, in the last 6 months.

My cancer has spread to the lining of my brain and spinal cord.

I am currently on medication for an infection.

I have bleeding from brain metastases.

I have a severe fistula.

I have had lung inflammation not caused by infection or radiation that didn't improve with steroids.

I have a history of Hepatitis B or currently have Hepatitis C.

I have an active autoimmune disease or a history of severe autoimmune disease.

I have an immune system disorder or I'm on long-term steroids.

I have a bleeding disorder or a high risk of severe bleeding.

I have a serious wound that is not healing.

I had brain radiotherapy less than a week before starting the study treatment.

I am not using or cannot use birth control.

I have a stomach or intestine condition that affects medication absorption.

My high blood pressure is not under control.

I have another cancer that is getting worse or needs treatment.

I have been diagnosed with HIV.

Participant Groups

The trial is testing Pembrolizumab combined with Lenvatinib in patients who have previously received PD-1/PD-L1 inhibitors but now have untreated brain metastases from either melanoma or RCC. It's a phase 2 study designed to evaluate the effectiveness and safety of this combination therapy.

Group I: Cohort 2: Renal Cell Carcinoma Experimental Treatment 2 Interventions

Participants who are Renal Cell Carcinoma (PD-1/PD-L1 experienced).

Group II: Cohort 1: Melanoma Experimental Treatment 2 Interventions

Participants who are melanoma (PD-1/PD-L1-experienced)

Lenvatinib is already approved in United States, European Union, 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

Find A Clinic Near You

Research locations nearby Select from list below to view details:

Yale University New Haven, CT

Who is running the clinical trial?

Yale University Lead Sponsor

Merck Sharp & Dohme LLC Industry Sponsor

References

1. England pubmed.ncbi.nlm.nih.gov

Lenvatinib plus pembrolizumab in patients with advanced gastric cancer in the first-line or second-line setting (EPOC1706): an open-label, single-arm, phase 2 trial. [2020] Pembrolizumab, an anti-PD-1 antibody, results in tumour response in around 15% of patients with advanced gastric cancer who have a PD-L1 combined positive score of at least 1. Lenvatinib, a multikinase inhibitor of VEGF receptors and other receptor tyrosine kinases, substantially decreased tumour-associated macrophages and increased infiltration of CD8 T cells, resulting in enhanced anti-tumour activity of PD-1 inhibitors in an in-vivo model. We aimed to assess the combination of lenvatinib plus pembrolizumab in patients with advanced gastric cancer in a phase 2 study.

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus lenvatinib as first-line therapy for advanced non-clear-cell renal cell carcinoma (KEYNOTE-B61): a single-arm, multicentre, phase 2 trial. [2023] Immunotherapy-based combinations including pembrolizumab plus lenvatinib are the standard of care for patients with first-line clear-cell renal cell carcinoma, but these combinations are not well characterised in non-clear-cell renal cell carcinoma. We aimed to assess the activity and safety of pembrolizumab plus lenvatinib as a first-line treatment for patients with advanced non-clear-cell renal cell carcinoma.

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

Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. [2022] Lenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. The efficacy of these regimens as compared with that of sunitinib is unclear.

4. 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] Pembrolizumab plus lenvatinib has shown antitumor activity and acceptable safety in patients with platinum-refractory urothelial carcinoma (UC).

5. Australia pubmed.ncbi.nlm.nih.gov

A case of metastatic renal cell carcinoma successfully treated with deferred cytoreductive nephrectomy following lenvatinib plus pembrolizumab combination therapy. [2023] Combination therapy using immuno-oncology drugs with tyrosine kinase inhibitors is increasingly important in the therapeutic strategy for metastatic renal cell carcinomas. Here, we report a case of metastatic renal cell carcinoma that was successfully treated with deferred cytoreductive nephrectomy following lenvatinib plus pembrolizumab combination therapy.

6. Germany pubmed.ncbi.nlm.nih.gov

A feasibility study of lenvatinib plus pembrolizumab in Japanese patients with advanced solid tumors. [2022] Combination treatment using lenvatinib (a multikinase inhibitor) plus pembrolizumab (a programmed death-1 immune checkpoint inhibitor) has shown efficacy in the treatment of endometrial and renal cell cancers. This phase 1b study investigated the tolerability and safety of lenvatinib plus pembrolizumab in Japanese patients with metastatic selected solid tumors.

7. 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] Lenvatinib plus pembrolizumab showed significantly improved progression-free and overall survival outcomes compared with sunitinib in patients with advanced renal cell carcinoma in the CLEAR study (NCT02811861). Here, we used CLEAR data to characterize common adverse reactions (ARs; adverse-event preferred terms grouped in accordance with regulatory authority review) associated with lenvatinib plus pembrolizumab and review management strategies for select ARs.

8. England pubmed.ncbi.nlm.nih.gov

The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. [2021] Tumor progression and immune evasion result from multiple oncogenic and immunosuppressive signals within the tumor microenvironment. The combined blockade of VEGF and inhibitory immune checkpoint signaling has been shown to enhance immune activation and tumor destruction in preclinical models. The LEAP clinical trial program is evaluating the safety and efficacy of lenvatinib (a multikinase inhibitor) plus pembrolizumab (a PD-1 inhibitor) across several solid tumor types. Preliminary results from ongoing trials demonstrate robust antitumor activity and durable responses across diverse tumor types with a manageable safety profile. Thus, lenvatinib plus pembrolizumab is anticipated to be an important potential new regimen for several solid cancers that currently have limited therapeutic options. Clinical trial registration: NCT03884101, NCT03713593, NCT03820986, NCT03776136, NCT03797326, NCT03829319, NCT03829332, NCT03976375, NCT04428151, NCT04199104, NCT03898180, NCT04246177 (ClinicalTrials.gov).