Phase 3 study of lenvatinib plus pembrolizumab for advanced endometrial cancer

Phase 1

• Conditions: Advanced Endometrial Cancer; MedDRA version: 20.0Level: PTClassification code 10014733Term: Endometrial cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-004387-35-FR
• Lead Sponsor: Eisai Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-04-19
• Last Update Posted: 7 January 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 780

Inclusion Criteria

1. Histologically confirmed diagnosis of endometrial carcinoma.
2. Documented evidence of advanced, recurrent or metastatic EC.
3. Radiographic evidence of disease progression after 1 prior systemic, platinum-based chemotherapy regimen for recurrent, metastatic or primary unresectable disease.
- Participants who progress <1 year after completion of prior adjuvant or neoadjuvant platinum-based chemotherapy are eligible without further systemic treatment.
- Participants who progress =1 year after completion of prior adjuvant or neoadjuvant platinum-based chemotherapy must receive 1 additional cytotoxic systemic treatment prior to enrollment in this study.
4. Available historical or fresh tumor biopsy specimen for determination of MMR status.
5. At least 1 measurable target lesion according to RECIST 1.1 and confirmed by BICR, including the following criteria:
- Non-nodal lesion that measures =1.0 cm in the longest diameter
- Lymph node (LN) lesion that measures as =1.5 cm in the short axis
- The lesion is suitable for repeat measurement using computed tomography/magnetic resonance imaging (CT/MRI). Lesions that have had external beam radiotherapy (EBRT) or locoregional therapy must show radiographic evidence of subsequent growth.
6. ECOG performance status of 0 or 1 within 3 days of starting study treatment.
7. Female participants age =18 years and considered an adult per local regulations at the time of informed consent.
8. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
a.) Not a WOCBP
OR
b.) 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.
9. The participant provides written informed consent for the study.
10. Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP =150/90 mm Hg at Screening and no change in antihypertensive medications within 1 week before C1D1.
11. Have adequate organ function. Specimens must be collected within 3 days prior to the start of study treatment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 180
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 600

Exclusion Criteria

1. Carcinosarcoma (malignant mixed Mullerian tumor), endometrial leiomyosarcoma and endometrial stromal sarcomas.
2. Participants with CNS metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment.
3. Active malignancy (except for endometrial cancer, definitively treated in-situ carcinomas, or basal or squamous cell carcinoma of the skin) within the past 24 months.
4. Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib.
5. Radiographic evidence of major blood vessel invasion/infiltration. The degree of tumor invasion/infiltration of major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy.
6. Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug.
7. Significant cardiovascular impairment within 12 months of the first dose of study drug: such as history of congestive heart failure greater than NYHA Class II, unstable angina, myocardial infarction or cerebrovascular accident stroke, or cardiac arrhythmia associated with hemodynamic instability.
8. Active infection (any infection requiring systemic treatment).
9. Participants who have not recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy.
10. Participants known to be positive for Human Immunodeficiency Virus (HIV). No HIV testing is required unless mandated by local heath authority.
11. Known active Hepatitis B or Hepatitis C. No testing for hepatitis B or C is required unless mandated by local health authority.
12. Has a history of (non-infectious) pneumonitis that required treatment with steroids, or has current pneumonitis.
13. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
14. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
15. 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.
16. Active autoimmune disease (with the exception of psoriasis) that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.
17. Females who are breastfeeding or pregnant at Screening or Baseline. A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
18. Greater than 1 prior systemic anticancer regimen (other than adjuvant or neoadjuvant) for advanced, recurrent, or metastatic endometrial cancer.
19. Prior anticancer treatment within 28 days (or 5 times the half-life time, whichever is shorter). All acute toxicities related to prior treatments must be resolved to

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified