Lenvatinib + Pembrolizumab + Fulvestrant for Breast Cancer
Recruiting in Palo Alto (17 mi)
+6 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
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
Breakthrough Therapy
Trial Summary
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.
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.
12345What 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.
12346Eligibility 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
+17 more
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.
+26 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Lenvatinib, Pembrolizumab, and FulvestrantExperimental Treatment3 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:
πͺπΊ Approved in European Union as Faslodex for:
- Hormone receptor-positive metastatic breast cancer
- Locally advanced breast cancer
πΊπΈ Approved in United States as Faslodex for:
- Hormone receptor-positive metastatic breast cancer
- Locally advanced breast cancer
π¨π¦ Approved in Canada as Faslodex for:
- Hormone receptor-positive metastatic breast cancer
- Locally advanced breast cancer
π―π΅ Approved in Japan as Faslodex for:
- Hormone receptor-positive metastatic breast cancer
- Locally advanced breast cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Memorial Sloan Kettering Bergen (Limited Protocol Activities)Montvale, NJ
Memorial Sloan Kettering Nassau (Limited Protocol Activities)Uniondale, NY
Memorial Sloan Kettering Cancer Center (All Protocol Activities)New York, NY
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)Middletown, NJ
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
References
Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial. [2020]Lenvatinib is a multikinase inhibitor of VEGFR1, VEGFR2, and VEGFR3, and other receptor tyrosine kinases. Pembrolizumab, an antibody targeting PD-1, has moderate efficacy in biomarker-unselected endometrial cancer. We aimed to assess the combination of lenvatinib plus pembrolizumab in patients with advanced endometrial carcinoma, after establishing the maximum tolerated dose in a phase 1b study.
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]Effective treatments are needed for melanoma that progresses on inhibitors of programmed cell death protein-1 (PD-1) or its ligand (PD-L1). We conducted the phase II LEAP-004 study to evaluate the combination of the multikinase inhibitor lenvatinib and the PD-1 inhibitor pembrolizumab in this population (ClinicalTrials.gov identifier: NCT03776136).
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]Pembrolizumab plus lenvatinib is a novel combination with promising efficacy in patients with advanced and recurrent endometrial cancer. This combination demonstrated high objective response rates in a single-arm phase 1b/2 trial of lenvatinib plus pembrolizumab in patients with advanced endometrial cancer (KEYNOTE-146/Study 111) after β€2 previous lines of therapy. In a randomized phase 3 trial of lenvatinib in combination with pembrolizumab versus treatment of physician's choice in patients with advanced endometrial cancer (KEYNOTE-775/Study 309), after 1β2 previous lines of therapy (including neoadjuvant/adjuvant), this combination improved objective response rates, progression-free survival, and overall survival compared with chemotherapy.
Pembrolizumab plus lenvatinib in second-line and third-line patients with pleural mesothelioma (PEMMELA): a single-arm phase 2 study. [2023]The combination of pembrolizumab, an anti-PD-1 antibody, and lenvatinib, an antiangiogenic multikinase inhibitor, shows synergistic activity in preclinical and clinical studies in solid tumours. We assessed the clinical activity of this combination therapy in patients with pleural mesothelioma who progressed after platinum-pemetrexed chemotherapy.
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).
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.