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Ovarian Clear Cell CarcinomaPhase 2NCT05296512

Pembrolizumab and Lenvatinib in Clear Cell Ovarian Cancer

A Phase 2 study testing Lenvatinib and Pembrolizumab in people with Ovarian Clear Cell Carcinoma and Gynecologic Cancer, run by Elizabeth K. Lee MD at 3 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This research study is being done to test the efficacy and safety of combining the study drugs pembrolizumab and lenvatinib in patients with clear cell ovarian cancer. The names of the study drugs involved in this study are: Lenvatinib Pembrolizumab Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Lenvatinib and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
3 sitesUnited States
Study dates
23 Sep 2022to 15 Nov 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

  • Participants must have histologically or cytologically confirmed recurrent or persistent clear cell carcinoma of the ovary (CCOC) (≥50% clear cell histology).
  • Participants must have measurable disease, defined as at least one lesion that can be accurately measured per RECIST v1.1 criteria. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  • Participants must have received at least one prior platinum-based chemotherapeutic regimen for primary management of disease.
  • Prior bevacizumab is allowed.
  • Prior use of immune checkpoint inhibitors (e.g. anti-PD-1, anti-PD-L1, anti-CTLA-4) is allowed for up to 30% of participants.
  • Unlimited prior lines for the treatment of recurrent or persistent disease are allowed.
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  • Age ≥18 years. Because no dosing or adverse event data are currently available on the use of the combination of pembrolizumab/lenvatinib in participants <18 years of age, children are excluded from this study.
  • ECOG performance status of 0 or 1 (Karnofsky performance scale ≥70%).
  • Participants must have adequate organ and marrow function as defined below:
  • absolute neutrophil count ≥1,500/μcL
  • hemoglobin ≥ 9g/dL (without use of erythropoietin; without packed RBC transfusion within preceding 2 weeks)
  • platelet count ≥100,000/μcL
  • total bilirubin ≤ institutional upper limit of normal (ULN) (in the absence of liver metastases) or ≤ 1.5 × institutional ULN (in the presence of liver metastases)
  • AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN (in the absence of liver metastases) or ≤5 × institutional ULN (in the presence of liver metastases)
  • creatinine ≤ 1.5 ×ULN OR glomerular filtration rate (GFR) ≥30mL/min per the CKD-EPI formula for participants with Cr >1.5×ULN. The CKD-EPI formula is calculated as: GFR = 141 × min (Scr /κ, 1)α × max(Scr /κ, 1)-1.209 × 0.993Age × 1.018 [if female] × 1.159 [if black] here: Scr is serum creatinine in mg/dL, κ is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr /κ or 1, and max indicates the maximum of Scr /κ or 1.
  • PT/INR, aPTT ≤ 1.5x ULN unless participant is receiving anticoagulant therapy and the PT/INR or aPTT is within the intended therapeutic range of the anticoagulant
  • Participants must have adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as a BP ≤ 140/90 at screening and no change in antihypertensive medications within 2 weeks prior to Cycle 1 Day 1.
  • Participants with known brain metastases are eligible if they have completed primary CNS-directed therapy (such as surgical resection or radiotherapy) and if they have remained clinically stable, asymptomatic, radiologically stable without evidence of progression for at least 4 weeks by repeat imaging, and have been off of steroids for at least 4 weeks prior to starting study treatment.
  • Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen, as determined after discussion with the PI, are eligible for this trial.
  • Archival tumor tissue must be available as 27 (25 unstained + 2 H\&E) freshly serially cut slides from formalin-fixed, paraffin-embedded (FFPE) tissue blocks. The most recent available tissue is preferred to archived tissue. If fewer than 27 slides are available, the participant may still be eligible pending discussion with the Sponsor-Investigator.
  • The effects of pembrolizumab and lenvatinib on the developing human fetus are unknown. For this reason and because these agents are known to be teratogenic, women of child-bearing potential* must have a negative serum or urine pregnancy test at the Screening and Cycle 1 Day 1 visits. Women of child-bearing potential and men must agree to use adequate contraception (see Appendix D) prior to study entry, for the duration of study participation, and for at least 30 days after last receipt of study therapy. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately.
  • -- Female participants are NOT considered to be of childbearing potential if they meet either criteria: (1) Post-menopausal, defined as amenorrheic for at least 12 consecutive months within the appropriate age group and without an alternative medical cause, OR; (2) Surgically sterilized (i.e. bilateral oophorectomy, bilateral tubal ligation or salpingectomy, or total hysterectomy)
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Prior use of lenvatinib.
  • Use of any immunosuppressive therapy, including steroids used for the purpose of systemic immunosuppression (with dosing exceeding 10mg daily of prednisone or equivalent), within 2 weeks prior to beginning study treatment. The use of steroids as physiologic replacement (e.g. for adrenal or pituitary insufficiency) is allowed. The use of inhaled steroids (e.g. for the treatment of asthma or seasonal allergies) is allowed. The use of prophylactic corticosteroids to avoid allergic reactions (e.g. to IV contrast dye) is allowed.
  • Anti-cancer treatment (chemotherapy, radiotherapy, or other investigational therapy) within 4 weeks prior to entering the study (6 weeks prior to study entry for nitrosoureas or mitomycin C).
  • Prior radiation therapy within 2 weeks of start of study drugs. Participants must have recovered from all radiation-related toxicities and must not require steroids. Participants must not have had radiation pneumonitis. Palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease is permitted, provided there is at least a 1-week washout prior to start of study drugs.
  • Use of herbal supplements, including but not limited to: cannabis, St. John's wort, gingko biloba, ginseng, saw palmetto, and ephedra. Herbal supplements must be stopped at least 1 week prior to beginning study treatment.
  • Residual toxicities from prior anti-cancer therapy that remain Grade > 1, with the exception of alopecia and peripheral neuropathy. Toxicities related to prior treatments must have resolved to Grade ≤1 to be eligible.
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  • Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines are allowed.
  • Major surgical procedures within 4 weeks of beginning study treatment are not allowed. Minor surgical procedures (with the exception of port placement) within 1 week of beginning study treatment are not allowed.
  • Subjects having >1+ proteinuria on urinalysis must undergo a 24-hour urine collection for quantitative assessment of proteinuria. Subjects with urine protein ≥1g/24 hours will be ineligible.
  • Evidence of bowel involvement.
  • Any gastrointestinal disorder that would interfere with the passage or absorption of oral medications. Participants must be able to swallow oral medications. Participants with an enteric tube (e.g. gastrostomy or jejunostomy tube), receiving total parenteral nutrition (TPN), or dependent on IV fluid support are ineligible.
  • Participants with significant cardiovascular impairment, including uncontrolled hypertension, congestive heart failure of New York Heart Association Grade II or above, unstable angina, myocardial infarction within the past 6 months, or serious cardiac arrhythmia within the past 6 months.
  • Resting corrected QT interval (QTc) interval using the Fridericia formula (QTcF) >450 ms for males or >470 ms for females."
  • Clinically significant bleeding within 4 weeks of beginning study treatment.
  • Active autoimmune disease requiring systemic treatment (e.g. use of steroids, immunosuppressive medications, or disease modifying agents) within the past 2 years.
  • Has a diagnosis of immunodeficiency.
  • Is known to be positive for Human Immunodeficiency Virus (HIV). Subjects with HIV, including those on antiretroviral therapy, are excluded due to risk of immunodeficiency and risk of overlapping hepatotoxicity between antiretroviral agents and lenvatinib.
  • Is known to be positive for Hepatitis B virus (HBV) or Hepatitis C virus (HCV). Participants are eligible if they have a history of HCV infection that has been treated and cured, with an undetectable viral load.
  • History of allogeneic tissue/solid organ transplant.
  • History of non-infectious pneumonitis/interstitial lung disease that required steroids, or has current pneumonitis/interstitial lung disease.
  • Participants with uncontrolled intercurrent illness, including but not limited to active infection and serious non-healing wounds or ulcers.
  • Participants with psychiatric illness/social situations that would limit compliance with study requirements.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to lenvatinib, pembrolizumab, or any of the study drug excipients.
  • Pregnant women are excluded from this study because pembrolizumab and/or lenvatinib are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with pembrolizumab and/or lenvatinib, breastfeeding should be discontinued if the mother is treated with either agent.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • University of Chicago Medicine

    Chicago, Illinois, 60637

  • Mayo Clinic Comprehensive Cancer Center

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: A Phase II Trial of Pembrolizumab and Lenvatinib in Patients With Recurrent or Persistent Clear Cell Carcinoma of the Ovary

This research study is being done to test the efficacy and safety of combining the study drugs pembrolizumab and lenvatinib in patients with clear cell ovarian cancer.

The names of the study drugs involved in this study are:

  • Lenvatinib
  • Pembrolizumab
Read the detailed description

This is an open label, non-randomized, single cohort phase II trial. Participants with recurrent or persistent clear cell ovarian carcinoma (CCOC) will be treated with the investigational combination of pembrolizumab and lenvatinib until progression of disease or unacceptable toxicity.

The names of the study drugs involved in this study are:

  • Lenvatinib
  • Pembrolizumab

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

Participants will receive study treatment until progression of disease or unacceptable toxicity. Participants will be followed for 36 months thereafter. It is expected that about 31 people will take part in this research study.

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drugs work in treating a specific disease. "Investigational" means that the drug is being studied. The U.S. Food and Drug Administration (FDA) has not approved lenvatinib or pembrolizumab for your specific disease but it has been approved for other uses.

Keywords
Ovarian Clear Cell Carcinoma, Gynecologic Cancer

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LenvatinibDrug

    Also called Lenvatinib mesilate, Lenvima

    Lenvatinib is an oral capsule medication that will be taken by mouth once daily, every day of each 21-day treatment cycle. Treatment will be administered on an outpatient basis.

  • PembrolizumabDrug

    Also called Keytruda

    Pembrolizumab will be administered intravenously (IV) on Day 1 of every 21-day treatment cycle. Treatment will be administered on an outpatient basis.

    Pembrolizumab will be given up to 35 cycles (approximately 24 months). Participants who stop pembrolizumab treatment with SD or better may be eligible for up to an additional 17 cycles (approximately 12 months) of pembrolizumab treatment ("Pembrolizumab Re-Treatment") if they progress after stopping pembrolizumab and while receiving lenvatinib.

Study groups in NCT05296512
Study groupRoleWhat they receive
PEMBROLIZUMAB and LENVATINIBExperimentalThe research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. The names of the study drugs involved in this study are: * Lenvatinib * Pembrolizumab Treatment will continue until progression of disease or unacceptable toxicity. Participants will be followed for up to 36 months after discontinuation of study treatment.
Receives: Drug: Lenvatinib; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate (ORR)

    The objective response rate (ORR) is defined as the proportion of participants achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment.

    Measured: ORR expected to be observed up to 3 years

  2. 6 Month Progression-free survival (PFS) Rate

    6-month PFS rate is the proportion of participants who are alive and progression-free at 6 months. Progression-free survival (PFS) based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death.

    Measured: Disease will be evaluated at baseline and every 3 cycles on treatment, where each cycle is 3 weeks. Relevant to this endpoint is the 6 month timepoint.

Secondary outcomes (10)

  1. Grade 3 or Higher Treatment-Related Toxicity Rate

    All grade 3 or higher adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv5 as reported on case report forms are counted. Rate is the proportion of treated participants experiencing at least one treatment-related grade 3 or higher AE of any type during the time of observation.

    Measured: AEs expected to be observed up to 3 years

  2. Median Progression-free survival (PFS)

    Median PFS based on the Kaplan-Meier method is defined as the median duration of time from study entry to documented disease progression (PD) or death.

    Measured: Disease is evaluated at baseline, every 3 cycles on treatment (each cycle is 3 weeks), and in follow-up every 6 months (off due to PD) or every 3 months (off not due to PD), up to 3 years.

  3. Clinical Benefit Rate (CBR)

    CBR is defined as the proportion of participants with Partial Response (PR) + Complete Response (CR) + Stable Disease (SD) ≥6 months per RECIST 1.1. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

    Measured: Disease will be evaluated every 3 cycles on treatment (each cycle is 3 weeks); Treatment continues until disease progression or unacceptable toxicity. Treatment duration is expected to be up to 3 years.

  4. Median Overall Survival (OS)

    OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.

    Measured: Survival is evaluated in follow-up every 6 months (off due to PD) or every 3 months (off not due to PD), up to 3 years.

  5. ORR by PD-L1 expression status

    PD-L1 expression at baseline is dichotomized as positive or negative per established scoring methods. ORR within PD-L1 expression status groups is the proportion of participants achieving CR + PR per RECIST 1.1 on treatment.

    Measured: ORR is expected to be observed up to 3 years

  6. [immune RECIST] Objective Response Rate (ORR)

    The objective response rate (ORR) is defined as the proportion of participants achieving complete response (iCR) or partial response (iPR) per immune-RECIST (iRECIST).

    Measured: [immune RECIST] ORR is expected to be observed up to 3 years

  7. [immune RECIST] 6 Month Progression-free survival (PFS) Rate

    6-month PFS rate is the proportion of participants who are alive and progression-free at 6 months. Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death, per immune-RECIST 1.1 (iRECIST) criteria.

    Measured: Disease will be evaluated at baseline and every 3 cycles on treatment, where each cycle is 3 weeks. Relevant to this endpoint is the 6 month timepoint.

  8. [immune RECIST] Median Progression-free Survival (PFS)

    Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) per immune-RECIST (iRECIST) or death.

    Measured: Disease is evaluated at baseline, every 3 cycles on treatment, and in follow-up every 6 months (off due to PD) or every 3 months (off not due to PD), up to 3 years

  9. [immune RECIST] Median Overall Survival (OS)

    OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive per immune-RECIST (iRECIST).

    Measured: Survival is evaluated in follow-up every 6 months (off due to PD) or every 3 months (off not due to PD), up to 3 years.

  10. [immune RECIST] clinical benefit rate (CBR)

    CBR is defined as Partial Response (iPR) + Complete Response (iCR) + Stable Disease (iSD) ≥6 months per immune -ECIST (iRECIST).

    Measured: Disease will be evaluated every 3 cycles on treatment; Treatment is continued until disease progression or unacceptable toxicity. Treatment duration is expected to be up to 3 years.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Mar 2022
  2. Study start23 Sep 2022
  3. Primary completion8 Sep 2026
  4. Study completion15 Nov 2028 (estimated)

Resources

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
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05296512
Sponsor's protocol ID
21-739
Status last verified
Dec 2025
First submitted
16 Mar 2022
Last updated
4 Nov 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lenvatinib and Pembrolizumab in people with Ovarian Clear Cell Carcinoma and Gynecologic Cancer, run by Elizabeth K. Lee MD at 3 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 23 inclusion and 24 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: under way, not looking for participants, as of the sponsor's last update on 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) (time frame: ORR expected to be observed up to 3 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05296512.

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 4 Nov 2026.

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