Lenvatinib + Pembrolizumab + Fulvestrant for Breast Cancer

Recruiting at 6 trial locations

Overseen By Komal Jhaveri, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: LHRH agonists

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Immunodeficiency, Active infection, Autoimmune, others

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

Compensation: Varies

Number of Visits: 6

Duration: 24 weeks

43 Participants Needed

Trial Summary

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, you should discuss your current medications with the trial team to ensure they don't interfere with the study treatments.

What data supports the effectiveness of the drug combination Lenvatinib, Pembrolizumab, and Fulvestrant for breast cancer?

Research shows that the combination of Lenvatinib and Pembrolizumab has been effective in treating various advanced cancers, such as endometrial cancer and melanoma, by improving response rates and survival outcomes. This suggests potential effectiveness for other cancers, including breast cancer, when combined with Fulvestrant. ^{1 2 3 4 5}

What makes the drug combination of Lenvatinib, Pembrolizumab, and Fulvestrant unique for breast cancer treatment?

This drug combination is unique because it combines Lenvatinib, a multikinase inhibitor, and Pembrolizumab, an immune checkpoint inhibitor, which have shown promising results in other cancers like endometrial cancer, with Fulvestrant, a hormone therapy used in breast cancer. This approach targets cancer through multiple mechanisms, potentially offering a new option for patients with breast cancer. ^{1 2 3 4 6}

What is the purpose of this trial?

The purpose of this study is to test whether the combination of lenvatinib, pembrolizumab, and fulvestrant is a safe and effective treatment that causes few or mild side effects in people with ER+/HER2- metastatic breast cancer.

Research Team

Sherry Shen, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults with ER+/HER2- metastatic breast cancer who have stable brain metastases, not pregnant or breastfeeding, and have had no more than two chemotherapy treatments in the metastatic setting. They must agree to contraception if applicable and have adequate organ function. People can't join if they've used certain immune therapies, VEGF inhibitors like lenvatinib before, or had recent vaccines or other cancer treatments.

Inclusion Criteria

Additional requirements for pregnancy testing during and after study intervention

You are expected to live for at least 12 more weeks.

A WOCBP must have a negative urine pregnancy test within 72 hours before the first dose of study intervention. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

Exclusion Criteria

Your heart's electrical activity is too slow.

I cannot swallow pills.

I had radiotherapy less than 2 weeks before starting the study treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lenvatinib, pembrolizumab, and fulvestrant to assess safety and effectiveness

24 weeks

Pembrolizumab every 6 weeks, Fulvestrant every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants may continue treatment to determine long-term safety and efficacy

1 year

Treatment Details

Interventions

• Fulvestrant
• Lenvatinib
• Pembrolizumab

Trial Overview The study tests a combination of three drugs: Lenvatinib, Pembrolizumab, and Fulvestrant for safety and effectiveness in treating ER+/HER2- metastatic breast cancer. It aims to find out if this drug mix causes only mild side effects while being an effective treatment option.

Participant Groups

Group I: Lenvatinib, Pembrolizumab, and Fulvestrant Experimental Treatment 3 Interventions

This is an open-label phase Ib/II trial of lenvatinib (20mg orally PO daily) plus pembrolizumab (400mg IV Q6W) plus fulvestrant (500mg IM Q4W) in patients with unresectable, locally advanced/metastatic ER+/HER2- breast cancer.

Fulvestrant is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in United States as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in Canada as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in Japan as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

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 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 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 has shown promising efficacy in treating advanced endometrial cancer, with previous trials indicating improved objective response rates and survival outcomes compared to standard chemotherapy.

This ongoing phase 3 trial aims to determine if pembrolizumab plus lenvatinib is superior to the chemotherapy regimen of paclitaxel plus carboplatin in newly diagnosed patients, with a target enrollment of about 875 participants and results expected in 2022.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 3, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer: ENGOT-en9/LEAP-001. Marth, C., Tarnawski, R., Tyulyandina, A., 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]

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]

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]

References

1. England 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. [2020]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

Phase 3, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer: ENGOT-en9/LEAP-001. [2022]

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. [2021]

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

A feasibility study of lenvatinib plus pembrolizumab in Japanese patients with advanced solid tumors. [2022]