A Phase Ib/II Trial of Lenvatinib Plus Pembrolizumab Plus Fulvestrant in ER-positive/ HER2- Negative Metastatic Breast Cancer

Memorial Sloan Kettering Cancer Center7 sites in 1 country49 target enrollmentDecember 29, 2023

ConditionsMetastatic Breast Cancer

InterventionsLenvatinib Pembrolizuma Fulvestrant

DrugsLenvatinib Pembrolizuma Fulvestrant

Overview

Phase: Phase 1
Intervention: Lenvatinib
Conditions: Metastatic Breast Cancer
Sponsor: Memorial Sloan Kettering Cancer Center
Enrollment: 49
Locations: 7
Primary Endpoint: The number of adverse events and dose-limiting toxicities to find the Recommended Phase 2 Dose (RP2D)
Status: Recruiting
Last Updated: 4 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

December 29, 2023

End Date

November 1, 2026

Last Updated

4 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Memorial Sloan Kettering Cancer Center

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male or female participants who are ≥18 years old with histologically confirmed diagnosis of unresectable locally advanced or MBC.
•Male participants or premenopausal females are eligible as long as they are on LHRH agonist for at least four weeks prior to starting trial therapy and commit to continue LHRH agonist for as long as patient is receiving trial therapy or medical contraindications arise
•Patients diagnosed with ER+ (ER \>1%), HER2- breast cancer as per American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.
•Progressed on at least 1 prior endocrine therapy combined with CDK 4/6 inhibitor. Prior fulvestrant therapy is permitted.
•Have not received more than 2 lines of chemotherapy in the metastatic setting.
•Stable previously treated brain metastases i.e. without radiological evidence of progression for at least 4 weeks (note that repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at
•Life expectancy of ≥12 weeks.
•A newly obtained biopsy of non-irradiated tumor must be available prior to the first dose of study drug for biomarker analysis. Patients with inaccessible tumors for biopsy specimens can be enrolled without a biopsy (if archival tissue is available within the previous 6-12 months) upon consultation and agreement by the Principal Investigator. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are favored over slides and fresh tissue biopsies are preferred over archival tissue
•The participant provides written informed consent for the trial.
•Have measurable disease based on RECIST 1.

Exclusion Criteria

•Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
•Prior exposure to lenvatinib or any other VEGF-directed anti-angiogenic agent.
•Has received prior systemic anti-cancer therapy including investigational agents within 2 weeks prior to allocation. All acute toxicities related to prior systemic treatments must be resolved to Grade ≤1, except for alopecia and Grade ≤2 peripheral neuropathy.
•Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
•Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of non-live-attenuated vaccines is permitted.
•Note: please refer to Section 10.5 for information on COVID-19 vaccines
•Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 2 weeks prior to the first dose of study intervention.
•Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in doses \>10 mg daily of oral prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. Inhaled, intranasal, intra-articular, or topical steroid use are allowed.
•Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
•Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.

Arms & Interventions

Lenvatinib, Pembrolizumab, and Fulvestrant

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.

Intervention: Lenvatinib

Lenvatinib, Pembrolizumab, and Fulvestrant

Intervention: Pembrolizuma

Lenvatinib, Pembrolizumab, and Fulvestrant

Intervention: Fulvestrant

Outcomes

Primary Outcomes

The number of adverse events and dose-limiting toxicities to find the Recommended Phase 2 Dose (RP2D)

Time Frame: 1 year

of the combination of lenvatinib plus pembrolizumab plus fulvestrant and to confirm the AEs will be graded using National Cancer Institute (NCI) CTCAE Version v5.0. Investigators will decide the probability of the event being related to one, two or all three drugs as to whether dose modification of lenvatinib is required.MTD/RP2D of the triplet.