Pembrolizumab and Lenvatinib in Advanced Cervical Cancer

NCT04865887 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: STUDY00003849MK-3475-A70
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 4

Brief Summary

This is a phase II trial of combination therapy of pembrolizumab and lenvatinib in patients with locally advanced or metastatic cervical cancer that had failed first line of therapy. The hypothesis is the combination of lenvatinib and pembrolizumab will overcome vascular endothelial growth factor (VEGF)-mediated immunosuppression to enhance the response of patients with locally advanced or metastatic cervical cancer.

Conditions

Cervical Cancer; Metastatic Cervical Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  To evaluate the clinical activity (as assessed by objective response rate \[ORR\]) of specific pembrolizumab-lenvatinib combination.

  up to 2 years

Secondary Outcomes (5)

• Duration of response

  up to 2 years

• Progression Free survival

  up to 2 years

• Overall survival

  Cycle 1 Day 1, Day 1 of each cycle (each cycle is 21 days), every 12 weeks after end of treatment

• Incidence of adverse events

  Day 1 of each cycle (each cycle is 21 days), up to 2 years

• Incidence of study drug discontinuation due to Adverse Events

  Day 1 of each cycle (each cycle is 21 days), up to 2 years

Study Arms (1)

Pembrolizumab with Lenvatinib

EXPERIMENTAL

Drug: Pembrolizumab; Drug: Lenvatinib

Interventions

Pembrolizumab DRUG

200mg, every 3 weeks, IV infusion

Pembrolizumab with Lenvatinib

Lenvatinib DRUG

20 mg (2 capsules x10mg), daily, orally

Pembrolizumab with Lenvatinib

Eligibility Criteria

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

You may qualify if:

• Female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of locally advanced or metastatic cervical cancer will be enrolled in this study.
• Patients with progression or intolerance to at least one line of therapy in the locally advanced or metastatic setting will be eligible for this study.
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) as defined OR
• A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.
• The participant (or legally acceptable representative if applicable) 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 provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue. Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date slides are cut.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 28 days prior to the date of treatment initiation.
• Have adequate organ function as defined. Specimens must be collected within 28 days prior to the start of study treatment.
• Absolute neutrophil count (ANC) ≥1500/µL
• Platelets ≥100 000/µL
• Hemoglobin ≥9.0 g/dL
• Creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN
• Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN

You may not qualify if:

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment initiation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent.
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Has received prior radiotherapy within 2 weeks of start of study treatment. 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 prior to the first dose of study drug. Administration of killed vaccines is allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• 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 (e.g. breast carcinoma) 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 the 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 treatment.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab or lenvatinib and/or any of their excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.
• Has a known history of Human Immunodeficiency Virus (HIV).
• Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.

Sponsors & Collaborators

• Georgetown University: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (4)

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

RECRUITING

Medstar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

WITHDRAWN

Georgia Cancer Center at Augusta University

Augusta, Georgia, 30912, United States

RECRUITING

John Theurer Cancer Center at Hackensack UMC

Hackensack, New Jersey, 07601, United States

RECRUITING

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

pembrolizumab; lenvatinib

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Samir Khleif, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2021
• First Posted: April 29, 2021
• Study Start: October 7, 2022
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: October 7, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)