A Study of Pembrolizumab With Lenvatinib in Women With Advanced Uterine Carcinosarcoma

NCT05147558 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 21-273
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study to find out whether the combination of lenvatinib and pembrolizumab is an effective treatment for advanced uterine carcinosarcoma. The researchers will also do tests to find out whether biomarkers in the blood can predict the cancer's response to the study treatment. A biomarker is a biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition

Conditions

Uterine Carcinosarcoma; Advanced Uterine Carcinosarcoma

Keywords

Pembrolizumab; Lenvatinib; 21-273

Outcome Measures

Primary Outcomes (2)

• overall response rate (ORR)

  RECIST v 1.1 assessments

  1 year

• progression free survival (PFS)

  is defined as the duration of time from start of treatment until progression or death whichever occurs first. Patients without documented progression or death will be censored at last follow up date.

  week 27

Study Arms (1)

Pembrolizumab With Lenvatinib

EXPERIMENTAL

Lenvatinib (20mg once daily orally) in combination with Pembrolizumab (200mg every 3 weeks, intravenously)

Drug: Pembrolizumab; Drug: Lenvatinib

Interventions

Pembrolizumab DRUG

Pembrolizumab (200mg every 3 weeks, intravenously)

Pembrolizumab With Lenvatinib

Lenvatinib DRUG

Lenvatinib (20mg once daily orally)

Pembrolizumab With Lenvatinib

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Women With Advanced Uterine Carcinosarcoma.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed persistent/recurrent uterine or ovarian carcinosarcomas. For this study, a histological diagnosis of carcinosarcoma must include identifying high grade malignant epithelial and mesenchymal components. The mesenchymal component can be homologous or heterologous.
• Patients with known microsatellite stable (MSS), microsatellite instability high (MSI-H), mismatch repair proficient (pMMR) and mismatch repair deficient (dMMR) uterine or ovarian carcinosarcoma are eligible.
• Patients must have had 1 prior platinum-based chemotherapy regimen and could have received up to 3 prior lines of systemic therapy.
• All chemotherapy must have been completed at least 3 weeks prior to the start of study therapy
• Hormonal Therapy will NOT count as prior treatment line.
• All hormonal therapy for treatment of endometrial or ovarian carcinosarcomas must be discontinued at least one week prior to start of study therapy.
• Prior Bevacizumab also allowed and must be at least 3 weeks prior to the start of study therapy.
• Prior Parp-inhibitors also allowed and must be at least 3 weeks prior to the start of study therapy.
• Age ≥18 years at the time of informed consent
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.
• participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a WOCBP as defined in Appendix B or
• A WOCBP who agrees to follow the contraceptive guidance in Appendix B during the treatment period and for at least 120 days after the last dose of study treatment(s) (MK and or any active comparator/combination) plus 30 days (a menstruation cycle) for study treatments with risk of genotoxicity\] after the last dose of study treatment.
• The participant (provides written informed consent for the study.
• Have an Eastern Cooperative Oncology Group ECOG performance status of 0 or 1.

You may not qualify if:

• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• Has received prior therapy with a VEGF TKI to include but not limited to: lenvatinib, lucitinib, cederinib, and cabozantonib
• Has participated in a study of an investigational agent and received cancer directed study therapy within 4 weeks prior to start of study treatment.
• 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.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
• 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.
• Steroids as CT scan contrast premedication is allowed
• The use of inhaled or topical corticosteroids is allowed
• The use of mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
• Has a known additional malignancy that is progressing or has required active treatment within the past 2 years.
• Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) 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 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited protocol activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limited protocol activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Limited protocol activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Suffolk- Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited protocol activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited protocol activities)

Rockville Centre, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Interventions

pembrolizumab; lenvatinib

Study Officials

• Vicky Makker, MD

  Memorial Sloan Kettering Cancer Center

  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

Model Details: This is an open label, single institution, phase II study

Study Record Dates

• First Submitted: November 15, 2021
• First Posted: December 7, 2021
• Study Start: December 23, 2021
• Primary Completion (Estimated): December 23, 2026
• Study Completion (Estimated): December 23, 2026
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (7)