A Study of Lenvatinib, Pembrolizumab, and Fulvestrant in People With Breast Cancer

NCT06110793 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 23-274
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 7

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.

Conditions

Metastatic Breast Cancer

Keywords

ER-positive/ HER2- negative; Lenvatinib; Pembrolizumab; Fulvestrant; 23-274

Outcome Measures

Primary Outcomes (1)

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

  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.

  1 year

Secondary Outcomes (1)

• Overall response rate (ORR)

  24 weeks

Study Arms (1)

Lenvatinib, Pembrolizumab, and Fulvestrant

EXPERIMENTAL

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.

Drug: Lenvatinib; Drug: Pembrolizuma; Drug: Fulvestrant

Interventions

Lenvatinib DRUG

20mg orally PO daily

Lenvatinib, Pembrolizumab, and Fulvestrant

Pembrolizuma DRUG

400mg IV Q6W

Lenvatinib, Pembrolizumab, and Fulvestrant

Fulvestrant DRUG

500mg IM Q4W

Lenvatinib, Pembrolizumab, and Fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
• Have adequately controlled BP with or without antihypertensive medications, defined as BP ≤150/90 mm Hg with no change in antihypertensive medications within 1 week prior to randomization.
• Have adequate organ function. Specimens must be collected within 14 days prior to the start of study intervention.
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
• Is not a woman of childbearing potential (WOCBP) OR

You may not qualify if:

• 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.
• Has a history or evidence of active pneumonitis or interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring antibiotics.
• Has a known history of Human Immunodeficiency Virus (HIV) infection.
• Has an inability to swallow capsules.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Breast Neoplasms

Interventions

lenvatinib; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Sherry Shen, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sherry Shen, MD

CONTACT

646-888-5299; shens1@mskcc.org

Komal Jhaveri, MD

CONTACT

646-888-5157

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase Ib/II open label study

Study Record Dates

• First Submitted: October 26, 2023
• First Posted: November 1, 2023
• Study Start: December 29, 2023
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: May 13, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

US (7)