Pembrolizumab + Lenvatinib for Advanced Cancers with Brain Metastases

Overseen By Jordi Ahnert

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anticoagulants, Corticosteroids

Disqualifiers: Hepatocellular carcinoma, Spinal cord compression, 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: 12 weeks

104 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of combining two drugs, pembrolizumab (an immunotherapy drug) and lenvatinib (a targeted therapy), for individuals with certain advanced cancers that have spread to the brain. The study focuses on three groups: those with triple-negative breast cancer, non-small cell lung cancer, and other solid tumors such as kidney or endometrial cancers. Suitable candidates for this trial include those diagnosed with any of these cancers and possessing at least one measurable brain tumor that remains untreated. The researchers aim to determine if the drug combination can effectively shrink brain tumors. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you should not be on certain treatments like systemic steroids above a specific dose or have received certain therapies recently. It's best to discuss your current medications with the study team to see if any adjustments are needed.

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

Research has shown that the combination of pembrolizumab and lenvatinib is generally safe, based on several studies. In past research, patients experienced side effects similar to those in earlier studies of these drugs, indicating that the treatment is usually well-tolerated. Common side effects include tiredness, high blood pressure, and changes in liver function tests, but proper care can typically manage these.

Experts have also studied patients with cancer that has spread to the brain who received this combination. They found that the side effects were expected and typical for treatments like this.

For those considering joining a clinical trial for this treatment, it's important to know that while side effects exist, they are similar to those seen in other studies of these drugs, suggesting the treatment is reasonably safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Pembrolizumab and Lenvatinib for treating advanced cancers with brain metastases because these drugs work together in a novel way. Pembrolizumab is an immunotherapy that boosts the body's natural defenses to fight cancer, while Lenvatinib is a targeted therapy that blocks proteins that help tumors grow and spread. This dual-action approach is different from traditional treatments like chemotherapy and radiation, which can be less specific and more taxing on the body. The combination of these two drugs offers a promising new strategy that might improve outcomes for patients with difficult-to-treat brain metastases, providing hope where options are currently limited.

What evidence suggests that this trial's treatments could be effective for advanced cancers with brain metastases?

Research has shown that the combination of pembrolizumab and lenvatinib effectively treats various advanced cancers. This trial will evaluate this combination specifically for patients with solid tumors that have spread to the brain. The treatment has proven particularly successful in kidney cancer, leading to long-lasting improvements. Patients with untreated cancer that has spread to the brain have also benefited from this approach. The combination strengthens the immune system (the body's defense against illness) and cuts off the blood supply to tumors, helping to shrink them. These promising results support further research into using pembrolizumab and lenvatinib for treating solid tumors that have spread to the brain. ^{6 7 8 9 10}

Who Is on the Research Team?

Jordi Rodon Ahnert

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults with certain types of cancer (TNBC, NSCLC, or other solid tumors) that have spread to the brain. They must have good kidney function, controlled blood pressure, and no serious liver issues. Patients should not be pregnant or breastfeeding and must agree to use contraception. Those with specific lung cancer mutations or untreated spinal cord compression are excluded.

Inclusion Criteria

Patients must provide written informed consent

Hepatitis B and C screening tests are required under specific conditions

I have brain metastases with little to no symptoms.

Exclusion Criteria

I have taken specific medications before.

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

I have untreated spinal cord compression or cancer spread to the lining of my brain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab in combination with lenvatinib for solid tumors and brain metastases

12 weeks

Bi-weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Monthly visits (in-person)

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Lenvatinib
• Pembrolizumab

Trial Overview The trial is testing the combination of Pembrolizumab (an immunotherapy drug) and Lenvatinib (a medication that inhibits tumor blood vessel growth) in patients with different cancers that have metastasized to the brain. The goal is to see how well this combo works on brain tumors using a two-stage study design.

How Is the Trial Designed?

Group I: Cohort 3 Experimental Treatment 2 Interventions

Patients with other solid tumor types and brain metastases

Group II: Cohort 2 Experimental Treatment 2 Interventions

Patients with NSCLC and brain metastases

Group III: Cohort 1 Experimental Treatment 2 Interventions

Patients with TNBC and brain metastases

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

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

In a study involving 137 patients with advanced solid tumors, the combination of lenvatinib and pembrolizumab showed a manageable safety profile, with common side effects including fatigue, diarrhea, and hypertension.

The treatment demonstrated promising antitumor activity, with objective response rates at week 24 ranging from 25% to 63% across different cancer types, indicating its potential effectiveness in various advanced cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IB/II Trial of Lenvatinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma, Endometrial Cancer, and Other Selected Advanced Solid Tumors. Taylor, MH., Lee, CH., Makker, V., et al.[2021]

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 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 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]

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 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 a phase 2 trial involving 29 patients with advanced gastric cancer, the combination of lenvatinib and pembrolizumab resulted in a promising objective response rate of 69%, indicating significant anti-tumor activity.

The treatment was generally well-tolerated, with the most common grade 3 adverse events being manageable, such as hypertension and proteinuria, and no serious treatment-related complications or deaths reported.

NCBI (Pubmed)

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. Kawazoe, A., Fukuoka, S., Nakamura, Y., et al.[2020]

In a phase 2 study involving 54 patients with advanced endometrial cancer, the combination of lenvatinib and pembrolizumab resulted in a 39.6% objective response rate at week 24, indicating significant anti-tumor activity.

The treatment was generally well-tolerated, with serious adverse events occurring in 30% of patients, including one treatment-related death; however, the safety profile was consistent with previous studies of the individual drugs, except for a higher incidence of hypothyroidism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial. Makker, V., Rasco, D., Vogelzang, NJ., et al.[2020]

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]

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 lenvatinib, a multikinase inhibitor, and pembrolizumab, a PD-1 inhibitor, shows promising antitumor activity and durable responses in various solid tumors, as indicated by preliminary results from the LEAP clinical trial program.

This combination therapy has a manageable safety profile, suggesting it could be a valuable new treatment option for solid cancers that currently have limited therapeutic alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. Taylor, MH., Schmidt, EV., Dutcus, C., et al.[2021]

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