Resumen

The purpose of this study is to compare the efficacy of pembrolizumab + lenvatinib to chemotherapy in female participants with Stage III, IV, or recurrent endometrial carcinoma. It is hypothesized that the combination of pembrolizumab + lenvatinib will be superior to chemotherapy for progression-free survival (PFS) per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) by blinded independent central review (BICR). It is also hypothesized that the combination of pembrolizumab + lenvatinib will be superior to chemotherapy for overall survival (OS). As of Amendment 7 eligible participants on study completion will be able to transition to an extension study, if available, in which they can continue to receive pembrolizumab monotherapy, lenvatinib monotherapy, or a combination of both pembrolizumab and lenvatinib as received in the parent study.

Elegibilidad

Edad mínima: 18 YearsSexo: FEMALE

Criterios de inclusión

Has Stage III, Stage IV, or recurrent, histologically-confirmed endometrial carcinoma with disease that is either measurable or nonmeasurable but radiographically apparent, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR) (note: may have received prior chemotherapy only if administered concurrently with radiation; may have received prior radiation without concurrent chemotherapy; may have received prior hormonal therapy for treatment of endometrial carcinoma, provided that it was discontinued ≥1 week prior to randomization; and may have received 1 prior line of systemic platinum-based adjuvant and/or neoadjuvant chemotherapy)
Has provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion that was not previously irradiated, for determination of mismatch repair (MMR) status
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 7 days prior to the first dose of study intervention
Is not pregnant or breastfeeding, and is either not a woman of childbearing potential (WOCBP) or is a WOCBP who agrees to use contraception during the study and for ≥120 days after pembrolizumab, ≥30 days after lenvatinib, or ≥180 days after (chemotherapy) \[if a WOCBP, a pregnancy test will be required within 24 hours of first dose of study drug\]
Has adequately controlled blood pressure within 7 days prior to randomization
Has adequate organ function based on assessment within 7 days prior to the first dose of study intervention

Criterios de exclusión

Has carcinosarcoma (malignant mixed Műllerian tumor), endometrial leiomyosarcoma or other high grade sarcomas, or endometrial stromal sarcomas
Has a central nervous system (CNS) metastasis, unless local therapy (e.g., whole brain radiation therapy, surgery, or radiosurgery) has been completed and have discontinued use of corticosteroids for this indication for ≥4 weeks prior to starting study medication (major surgery within 3 weeks of the first dose of study drug will be exclusionary)
Has a known additional malignancy (other than endometrial carcinoma) that is progressing or has required active treatment in the last 3 years
Has gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib
Has a pre-existing Grade ≥3 gastrointestinal or nongastrointestinal fistula
Has radiographic evidence of major blood vessel invasion/infiltration
Has active hemoptysis (bright red blood at ≥0.5 teaspoon) within 3 weeks prior to the first dose of study intervention or tumor bleeding within 2 weeks prior to randomization
Has clinically significant cardiovascular disease within 12 months from first dose of study intervention including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction or cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability
Has any infection requiring systemic treatment
Has not recovered adequately from any toxicity and/or complications from major surgery prior to randomization
Has a known history of human immunodeficiency virus (HIV) infection (HIV test is required at screening)
Has a known history of hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known active hepatitis C virus (HCV) \[defined as HCV ribonucleic acid (RNA) is detected\] (hepatitis B and C testing is required at screening only when mandated by local health authority)
Has a history of (noninfectious) pneumonitis that required treatment with steroids, or has current pneumonitis
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study
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 randomization
Has an active autoimmune disease (with the exception of psoriasis) that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
Has received prior systemic chemotherapy in any setting for the treatment of endometrial carcinoma (note: prior chemotherapy administered concurrently with radiation is permitted)
Has received prior radiotherapy within 4 weeks prior to randomization (participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis - a 2-week washout is permitted for palliative radiation to non-CNS disease and vaginal brachytherapy)
Has received prior hormonal therapy for the treatment of endometrial carcinoma within 1 week of randomization
Has received prior therapy with any treatment targeting vascular endothelial growth factor (VEGF)-directed angiogenesis, an anti-programmed cell death (PD)-1, anti-PD ligand (L)1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137)
Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention
Has known intolerance to study intervention (or any of the excipients)
Has had an allogenic tissue/solid organ transplant
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 randomization

Intervenciones

drug

Lenvatinib

Lenvatinib 4 mg or 10 mg capsules at a total daily dose of 20 mg taken by mouth once per day.

biological

Pembrolizumab

Pembrolizumab 200 mg intravenous (IV) infusion given on Day 1 of each cycle.

drug

Paclitaxel

Paclitaxel 175 mg/m\^2 IV infusion given on Day 1 of each cycle.

drug

Carboplatin

Carboplatin 10 mg/mL IV infusion at a total dose of are-under-the-curve (AUC) 6 (per Calvert's formula) given on Day 1 of each cycle.

Ubicaciones

IDIM Instituto de Diagnostico e Investigaciones Metabolicas ( Site 2607)

Caba, Buenos Aires, Argentina

Hospital Italiano de La Plata ( Site 2601)

La Plata, Buenos Aires, Argentina

Instituto de Investigaciones Clinicas Mar del Plata ( Site 2606)

Mar del Plata, Buenos Aires, Argentina

Hospital Aleman ( Site 2600)

Buenos Aires, Argentina

Hospital Italiano de Buenos Aires ( Site 2603)

Buenos Aires, Argentina

Centro Oncologico Riojano Integral ( Site 2605)

La Rioja, Argentina

A Phase 3 Randomized, Open-Label, Study of Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Versus Chemotherapy for First-line Treatment of Advanced or Recurrent Endometrial Carcinoma (LEAP-001)

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Lenvatinib

Pembrolizumab

Paclitaxel

Carboplatin

Ubicaciones

IDIM Instituto de Diagnostico e Investigaciones Metabolicas ( Site 2607)

Hospital Italiano de La Plata ( Site 2601)

Instituto de Investigaciones Clinicas Mar del Plata ( Site 2606)

Hospital Aleman ( Site 2600)

Hospital Italiano de Buenos Aires ( Site 2603)

Centro Oncologico Riojano Integral ( Site 2605)

Patrocinadores