Pembrolizumab and Lenvatinib in Advanced Cervical Cancer
NCT ID: NCT04865887
Last Updated: 2025-10-07
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
Recruitment Status
RECRUITING
Clinical Phase
PHASE2
Total Enrollment
35 participants
Study Classification
INTERVENTIONAL
Study Start Date
2022-10-07
Study Completion Date
2026-07-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Carboplatin-Paclitaxel-Pembrolizumab in Neoadjuvant Treatment of Locally Advanced Cervical Cancer
NCT04238988
Locally Advanced Cervical Cancer
UNKNOWN
PHASE2
Low-dose Pembrolizumab Plus Chemotherapy for the First-Line Treatment of Persistent, Recurrent, or Metastatic Cervical Cancer.
NCT06670911
Persistent, Recurrent, or Metastatic Cervical Cancer
RECRUITING
PHASE2
Nivolumab in Treating Patients With Persistent, Recurrent, or Metastatic Cervical Cancer
NCT02257528
Cervical Adenocarcinoma
Cervical Adenosquamous Carcinoma
Recurrent Cervical Carcinoma
+3 more
ACTIVE_NOT_RECRUITING
PHASE2
Pembrolizumab and Chemoradiation Treatment for Advanced Cervical Cancer
NCT02635360
Cervical Cancer
COMPLETED
PHASE2
Zimberelimab Plus Lenvatinib After Progression on Prior Immune Checkpoint Inhibitors for Advanced Cervical Cancer
NCT05824468
Cervical Cancer
Cervical Carcinoma
NOT_YET_RECRUITING
PHASE2
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
The primary endpoint of this phase II study is to determine the objective response rate (partial response \[PR\] + complete response \[CR\]) of specific pembrolizumab-lenvatinib combination therapy in patients with locally advanced or metastatic cervical cancer. The phase II portion of the trial will follow Simon's minimax two-stage design1.
In the Stage 1, 11 patients will be accrued. If 1 or fewer patients among these 11 patients achieve an objective response with the pembrolizumab-lenvatinib combination therapy, the combination therapy will be rejected and the trial stopped. However, if there are 2 or more patients who exhibit response in the Stage 1, then an additional 24 patients will be entered into the Stage 2, for a total of 35 patients in this phase II study. If 9 or more patients exhibit response among these 35 patients, then the treatment will be considered for further investigation. Any unplanned interim analysis will utilize the sequential conditional probability ratio test (SCPRT)2, which allows an early assessment of statistical evidence for both efficacy and futility, and provides a discordance probability that early trend could be reversed should the trial continue to enroll all 35 patients.
In the Stage 1, 11 patients will be accrued. If 1 or fewer patients among these 11 patients achieve an objective response with the pembrolizumab-lenvatinib combination therapy, the combination therapy will be rejected and the trial stopped. However, if there are 2 or more patients who exhibit response in the Stage 1, then an additional 24 patients will be entered into the Stage 2, for a total of 35 patients in this phase II study. If 9 or more patients exhibit response among these 35 patients, then the treatment will be considered for further investigation. Any unplanned interim analysis will utilize the sequential conditional probability ratio test (SCPRT)2, which allows an early assessment of statistical evidence for both efficacy and futility, and provides a discordance probability that early trend could be reversed should the trial continue to enroll all 35 patients.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Cervical Cancer
Metastatic Cervical Cancer
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
Allocation Method
NA
Intervention Model
SINGLE_GROUP
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Pembrolizumab with Lenvatinib
Group Type
EXPERIMENTAL
Pembrolizumab
Intervention Type
DRUG
200mg, every 3 weeks, IV infusion
Lenvatinib
Intervention Type
DRUG
20 mg (2 capsules x10mg), daily, orally
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Pembrolizumab
200mg, every 3 weeks, IV infusion
Intervention Type
DRUG
Lenvatinib
20 mg (2 capsules x10mg), daily, orally
Intervention Type
DRUG
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
1. 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.
2. 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.
3. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
1. Not a woman of childbearing potential (WOCBP) as defined OR
2. 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.
4. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
5. 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.
6. 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.
7. 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.
8. Have adequate organ function as defined. Specimens must be collected within 28 days prior to the start of study treatment.
1. Absolute neutrophil count (ANC) ≥1500/µL
2. Platelets ≥100 000/µL
3. Hemoglobin ≥9.0 g/dL
4. 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
5. Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN
6. AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
7. International normalized ratio (INR) OR prothrombin time (PT), Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
2. 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.
3. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
1. Not a woman of childbearing potential (WOCBP) as defined OR
2. 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.
4. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
5. 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.
6. 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.
7. 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.
8. Have adequate organ function as defined. Specimens must be collected within 28 days prior to the start of study treatment.
1. Absolute neutrophil count (ANC) ≥1500/µL
2. Platelets ≥100 000/µL
3. Hemoglobin ≥9.0 g/dL
4. 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
5. Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN
6. AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
7. International normalized ratio (INR) OR prothrombin time (PT), Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
Exclusion Criteria
1. 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.
2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. Has severe hypersensitivity (≥Grade 3) to pembrolizumab or lenvatinib and/or any of their excipients.
11. 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.
12. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
13. Has an active infection requiring systemic therapy.
14. Has a known history of Human Immunodeficiency Virus (HIV).
15. 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.
16. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
17. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
18. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
19. Has uncontrolled blood pressure (BP) (Systolic BP\>140 mmHg or diastolic BP\>90 mmHg) in spite of an optimized regimen of antihypertensive medication.
20. Has electrolyte abnormalities that have not been corrected.
21. Has significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke within 6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment at Screening.
22. Has bleeding or thrombotic disorders or subjects at risk for severe hemorrhage. The degree of tumor invasion/infiltration of major blood vessels (e.g. carotid artery) should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy.
23. Subjects having \> 1+ proteinuria on urine dipstick testing unless a 24-hour urine collection for quantitative assessment indicates that the urine protein is \<1 g/24 hours.
24. Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib.
25. Prolongation of QTc interval to \>480 ms.
2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. Has severe hypersensitivity (≥Grade 3) to pembrolizumab or lenvatinib and/or any of their excipients.
11. 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.
12. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
13. Has an active infection requiring systemic therapy.
14. Has a known history of Human Immunodeficiency Virus (HIV).
15. 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.
16. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
17. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
18. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
19. Has uncontrolled blood pressure (BP) (Systolic BP\>140 mmHg or diastolic BP\>90 mmHg) in spite of an optimized regimen of antihypertensive medication.
20. Has electrolyte abnormalities that have not been corrected.
21. Has significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke within 6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment at Screening.
22. Has bleeding or thrombotic disorders or subjects at risk for severe hemorrhage. The degree of tumor invasion/infiltration of major blood vessels (e.g. carotid artery) should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy.
23. Subjects having \> 1+ proteinuria on urine dipstick testing unless a 24-hour urine collection for quantitative assessment indicates that the urine protein is \<1 g/24 hours.
24. Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib.
25. Prolongation of QTc interval to \>480 ms.
Minimum Eligible Age
18 Years
Eligible Sex
FEMALE
Accepts Healthy Volunteers
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Merck Sharp & Dohme LLC
INDUSTRY
Sponsor Role
collaborator
Georgetown University
OTHER
Sponsor Role
lead
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Responsibility Role
SPONSOR
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Samir Khleif, MD
Role: PRINCIPAL_INVESTIGATOR
Georgetown University
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, United States
Site Status
RECRUITING
Medstar Washington Hospital Center
Washington D.C., District of Columbia, United States
Site Status
WITHDRAWN
Georgia Cancer Center at Augusta University
Augusta, Georgia, United States
Site Status
RECRUITING
John Theurer Cancer Center at Hackensack UMC
Hackensack, New Jersey, United States
Site Status
RECRUITING
Countries
Review the countries where the study has at least one active or historical site.
United States
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
MK-3475-A70
Identifier Type: OTHER
Identifier Source: secondary_id
STUDY00003849
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.
Induction Pembrolizumab and Chemotherapy Followed by Pembrolizumab Before Chemoradiation and Pembrolizumab Maintenance Compared to Standard Chemoradiation With Pembrolizumab Followed by Pembrolizumab Maintenance in High-Risk Cervical Cancer
NCT07061977
RECRUITING
PHASE3
A Study of Pembrolizumab (MK-3475) for First Line Treatment of Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck (MK-3475-048/KEYNOTE-048)
NCT02358031
COMPLETED
PHASE3
External Beam Radiation Therapy and Brachytherapy With Chemotherapy and Immunotherapy for the Treatment of Stage IVB Cervical Cancer
NCT06543576
RECRUITING
PHASE1/PHASE2
Envafolimab Combined With Endostar and Concurrent Chemoradiotherapy for Locally Advanced Primary Cervical Cancer
NCT05879796
NOT_YET_RECRUITING
Pembrolizumab Plus Olaparib in Patients With Recurrent Cervical Cancer
NCT04641728
UNKNOWN
PHASE2
Combination of PD-1 Monoclonal Antibody and HPV Vaccine in Patients With Cervical Cancer
NCT04096911
UNKNOWN
PHASE2
Pembrolizumab and Olaparib in Cervical Cancer Patients
NCT04483544
TERMINATED
PHASE2
A Study of Chemoradiation Plus Pembrolizumab for Locally Advanced Laryngeal Squamous Cell Carcinoma
NCT02759575
COMPLETED
PHASE1/PHASE2
Nituzumab Plus Serplulimab Combined With SBRT in Cervical Cancer
NCT06455072
RECRUITING
PHASE2
A Phase II Study of Serplulimab Plus Bevacizumab in Combination With Chemotherapy in 1L Treatment of Untreated Recurrent or Metastatic Cervical Cancer
NCT05444374
NOT_YET_RECRUITING
PHASE2
Real-world Study of Serplulimab in 2L and Above Treatment of Cervical Cancer
NCT05883670
RECRUITING
a Single Arm, Phase II Multicenter Clinical Trial to Evaluate the Efficacy and Safety of the Combination Therapy of Iparomlimab and Tuvonralima b and Chemotherapy ± Bevacizumab Induction Therapy Followed by Concurrent Chemoradiotherapy in Patients With Advanced Cervical Cancer .
NCT07035808
NOT_YET_RECRUITING
PHASE2
Study of Chemoradiotherapy With or Without Pembrolizumab (MK-3475) For The Treatment of Locally Advanced Cervical Cancer (MK-3475-A18/KEYNOTE-A18/ENGOT-cx11/GOG-3047)
NCT04221945
ACTIVE_NOT_RECRUITING
PHASE3
Clinical Study to Evaluate the Efficacy and Safety of Nab-Paclitaxel Combined With Cisplatin and Sintilimab in Neoadjuvant Treatment of Locally Advanced Cervical Cancer
NCT07088731
NOT_YET_RECRUITING
PHASE2
Pembrolizumab (MK-3475) Versus Standard Treatment for Recurrent or Metastatic Head and Neck Cancer (MK-3475-040/KEYNOTE-040)
NCT02252042
COMPLETED
PHASE3
PRGN-2009 in Combination With Pembrolizumab Versus Pembrolizumab in Patients With Recurrent or Metastatic Cervical Cancer
NCT06157151
RECRUITING
PHASE2
Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returning or Spreading Head and Neck Cancer After Previous Treatment
NCT06589804
RECRUITING
PHASE3
A Study to Test Whether Treatment With BI 770371 in Combination With Pembrolizumab With or Without Cetuximab Helps People With Head and Neck Cancer Compared With Pembrolizumab Alone
NCT06806852
RECRUITING
PHASE1
Serplulimab for Locally Advanced Cervical Cancer
NCT07340489
RECRUITING
PHASE2
Pembrolizumab Concurrent With and Following Carbon-ion Radiotherapy for Locally Advanced Cervical Adenocarcinoma
NCT06805864
NOT_YET_RECRUITING
PHASE2
Zimberelimab Combined With Concurrent Radiotherapy and Chemotherapy for Locally Advanced Cervical Cancer
NCT05437692
UNKNOWN
PHASE2
Gemcitabine in Treating Patients With Persistent or Recurrent Cancer of the Cervix
NCT00006224
TERMINATED
PHASE2
A Study of AK104 Plus Platinum-containing Chemotherapy±Bevacizumab as First-line Treatment for Persistent, Recurrent, or Metastatic Cervical Cancer
NCT04982237
ACTIVE_NOT_RECRUITING
PHASE3