Cervical CancerPhase 2NCT04865887
Pembrolizumab and Lenvatinib in Advanced Cervical Cancer
A Phase 2 study testing Pembrolizumab and Lenvatinib in people with Cervical Cancer and Metastatic Cervical Cancer, run by Georgetown University at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Cervical Cancer, Metastatic Cervical Cancer
- What is being tested?
- Pembrolizumab and Lenvatinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 4 sitesUnited States
- Study dates
- 7 Oct 2022to Jul 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
- AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
- 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
Who cannot join
- 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.
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- 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.
- 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.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- 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.
- Has uncontrolled blood pressure (BP) (Systolic BP>140 mmHg or diastolic BP>90 mmHg) in spite of an optimized regimen of antihypertensive medication.
- Has electrolyte abnormalities that have not been corrected.
- 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.
- 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.
- 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.
- Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib.
- Prolongation of QTc interval to >480 ms.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States4 sites, 3 recruiting
- Recruiting
Georgia Cancer Center at Augusta University
Augusta, Georgia, 30912
Emily Sarria, 706-721-5557, esarria@augusta.edu
Sharad Ghamande, MD
- Recruiting
John Theurer Cancer Center at Hackensack UMC
Hackensack, New Jersey, 07601
Oncology Clinical Research Referral Office, 551-996-1777, OncologyResearchReferral@hmhn.org
Donna McNamara, MD
- Recruiting
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
Jamie Magnanti, 202-687-3937, jm3821@georgetown.edu
Samir Khleif, MD
- Withdrawn
Medstar Washington Hospital Center
Washington D.C., District of Columbia, 20010
About this study
Official title: A Phase II Trial of Combination Therapy of Pembrolizumab and Lenvatinib in Patients With Locally Advanced or Metastatic Cervical Cancer
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.
Read the detailed description
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.
- Conditions
- Cervical Cancer, Metastatic Cervical Cancer
- Being tested
- Pembrolizumab, Lenvatinib
- Medical subject headings
- Uterine Cervical Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
200mg, every 3 weeks, IV infusion
LenvatinibDrug
20 mg (2 capsules x10mg), daily, orally
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab with Lenvatinib | Experimental | Not described Receives: Drug: Pembrolizumab; Drug: Lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate
To evaluate the clinical activity (as assessed by objective response rate [ORR]) of specific pembrolizumab-lenvatinib combination.
Measured: up to 2 years
Secondary outcomes (5)
Duration of response
To evaluate the clinical activity (as assessed by duration of response (DoR)) of pembrolizumab-lenvatinib combinations. DOR: length of time tumor continues to respond to the treatment.
Measured: up to 2 years
Progression Free survival
To evaluate the clinical activity (as assessed by progression-free survival [PFS]) of pembrolizumab-lenvatinib combinations. PFS: Time from treatment initiation to the first documented disease progression per response evaluation criteria in solid tumors (RECIST) 1.1 as assessed by local site or death, whichever occurs first.
Measured: up to 2 years
Overall survival
To evaluate the clinical activity (as assessed by overall survival [OS]) of pembrolizumab-lenvatinib combinations. OS: Time from treatment initiation to death due to any cause.
Measured: 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
To evaluate the safety and tolerability of pembrolizumab-lenvatinib combination:
Number of Participants Experiencing Adverse Events (AEs) according to NCI CTCAE Version 5.0.
Measured: Day 1 of each cycle (each cycle is 21 days), up to 2 years
Incidence of study drug discontinuation due to Adverse Events
To evaluate the safety and tolerability of pembrolizumab-lenvatinib combination: Number of Participants Discontinuing Study Drug Due to AEs.
Measured: Day 1 of each cycle (each cycle is 21 days), up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2021
- Study start7 Oct 2022
- Primary completionDec 2027 (estimated)
- Study completionJul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cervical CancerStudies of the same condition, open and under way.
- More trials run by Georgetown UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Georgetown University
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Samir Khleif, MD, Principal investigator, Georgetown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04865887
- Sponsor's protocol ID
- STUDY00003849
- Other IDs
- MK-3475-A70
- Status last verified
- Sep 2026
- First submitted
- 16 Apr 2021
- Last updated
- 10 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Combination Therapy of Pembrolizumab and Lenvatinib in Patients With Locally Advanced or Metastatic Cervical Cancer
- ClinicalTrials.gov ID
- NCT04865887
- Acronym / sponsor ID
- STUDY00003849
- Conditions
- Cervical Cancer, Metastatic Cervical Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Georgetown UniversityUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 7 Oct 2022 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Jul 2028 (estimated)
- First posted
- 29 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab with Lenvatinib | Experimental | Drug: Pembrolizumab, Drug: Lenvatinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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:
- 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.
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pembrolizumab200mg, every 3 weeks, IV infusion | Drug | Pembrolizumab with Lenvatinib |
| Lenvatinib20 mg (2 capsules x10mg), daily, orally | Drug | Pembrolizumab with Lenvatinib |
Primary outcome
Objective Response Rate
Time frame: up to 2 years
To evaluate the clinical activity (as assessed by objective response rate [ORR]) of specific pembrolizumab-lenvatinib combination.
5 secondary outcomes
Duration of response
Time frame: up to 2 years
Progression Free survival
Time frame: up to 2 years
Overall survival
Time frame: 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
Time frame: Day 1 of each cycle (each cycle is 21 days), up to 2 years
Incidence of study drug discontinuation due to Adverse Events
Time frame: Day 1 of each cycle (each cycle is 21 days), up to 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
MedStar Georgetown University Hospital
Washington D.C., United States
John Theurer Cancer Center at Hackensack UMC
Hackensack, United States
Samir Khleif, MD principal investigator
Georgetown University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab and Lenvatinib in people with Cervical Cancer and Metastatic Cervical Cancer, run by Georgetown University at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (time frame: up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2026.