Pembrolizumab and Lenvatinib in Clear Cell Ovarian Cancer

NCT05296512 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 21-739
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief 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

Conditions

Ovarian Clear Cell Carcinoma; Gynecologic Cancer

Keywords

Ovarian Clear Cell Carcinoma; Gynecologic Cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  ORR expected to be observed up to 3 years

• 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.

  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)

• Grade 3 or Higher Treatment-Related Toxicity Rate

  AEs expected to be observed up to 3 years

• Median Progression-free survival (PFS)

  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.

• Clinical Benefit Rate (CBR)

  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.

• Median Overall Survival (OS)

  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.

• ORR by PD-L1 expression status

  ORR is expected to be observed up to 3 years

Study Arms (1)

PEMBROLIZUMAB and LENVATINIB

EXPERIMENTAL

The 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.

Drug: Lenvatinib; Drug: Pembrolizumab

Interventions

Lenvatinib DRUG

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.

Also known as: Lenvatinib mesilate, Lenvima

PEMBROLIZUMAB and LENVATINIB

Pembrolizumab DRUG

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.

Also known as: Keytruda

PEMBROLIZUMAB and LENVATINIB

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Elizabeth K. Lee MD: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (3)

University of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Mayo Clinic Comprehensive Cancer Center

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Interventions

lenvatinib; pembrolizumab

Study Officials

• Elizabeth K Lee, MD

  Dana-Farber Cancer Institute

  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 INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: March 16, 2022
• First Posted: March 25, 2022
• Study Start: September 23, 2022
• Primary Completion (Estimated): September 23, 2026
• Study Completion (Estimated): November 15, 2028
• Last Updated: December 16, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (3)