Triple negative breast cancer (TNBC), ovarian cancer, gastric cancer, colorectal cancer (CRC), glioblastoma (GBM), or biliary tract cancers (BTC) MedDRA version: 20.0 Level: PT Classification code 10028997 Term: Neoplasm malignant System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Have a histologically or cytologically-documented, advanced (metastatic and/or unresectable) solid tumor that is incurable and for which prior standard systemic therapy has failed in one of the following cohorts: Cohort A Triple-Negative Breast Cancer (TNBC) Cohort B Ovarian Cancer Cohort C Gastric Cancer Cohort D Colorectal Cancer (non-MSI-H/pMMR tumor) Cohort E Glioblastoma (GBM) Cohort F Biliary Tract Cancer (BTC) (intrahepatic, extrahepatic cholangiocarcinoma and gall bladder cancer; excludes Ampulla of Vater) 2. Participants must have fulfilled cohort-specific requirements regarding prior (line of therapy) treatments. 3. Participants must have progressed on or since the last treatment. 4. Have measurable disease per RECIST 1.1 (RANO for the GBM cohort) as assessed by the local site investigator/radiology and confirmed by BICR. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. 5. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue. 6. Participant are at least 18 years of age; male or female for Gastric Cancer, GBM, TNBC, CRC and BTC cohorts; Female only for Ovarian Cancer cohort. 7. Life expectancy of 12 weeks or more. 8. Male Participants: Agree to use contraception as detailed in the protocol during the treatment period and for at least 120 days after the last dose of study intervention and refrain from donating sperm during this period. 9. Female Participants: Not be pregnant or breastfeeding, and at least 1 of the following conditions applies: a. Not be a woman of childbearing potential (WOCBP) OR b. A WOCBP must agree to follow the contraceptive guidance during the treatment period (or 14 days prior to the initiation of study medication for oral contraception) and for at least 120 days after the last dose of study intervention. 10. The participant (or legally acceptable representative if applicable) provides written informed consent for the study. 11. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 7 days of treatment initiation 12. Have adequate organ function. 13. 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. Other cancer-specific inclusion criteria- please refer to the Protocol 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 90 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 90
Exclusion criteria
Exclusion criteria: 1. Has presence of gastrointestinal condition including malabsorption that might affect the absorption of lenvatinib. 2. Radiographic evidence of major blood vessel invasion/infiltration. 3. Clinical significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug. 4. Has significant cardiovascular impairment within 12 months of the first dose of study drug. 5. Has a history of arterial thromboembolism within 12 months of start of study drug. 6. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. 7. Serious nonhealing wound, ulcer or bone fracture. 8. Biologic response modifiers (eg, granulocyte colony-stimulating factor) within 4 weeks before study entry. 9. Has received prior therapy with lenvatinib, 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). 10. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks or 5 times the half-life time, whichever is shorter prior to study treatment start. 11. If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. 12. Has received prior radiotherapy within 2 weeks of start of study treatment. 13. Has received a live vaccine within 30 days prior to the first dose of study drug. 14. Known intolerance to study treatment (or any of the excipients). 15. 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 the first dose of study intervention. 16. Participants with proteinuria >1+ on urine dipstick testing will undergo 24-h urine collection for quantitative assessment of proteinuria. 17. Prolongation of QTc interval (calculated using Fridericia’s formula) to >480 ms. 18. Has left ventricular ejection fraction (LVEF) <55 as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO). 19. 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 the first dose of study drug. 20. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. 21. Has tumors involving the brain stem. 22. Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients. 23. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). 24. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. 25. Has an active infection requiring systemic therapy. 26. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: A) To evaluate objective response rate (ORR) of pembrolizumab (MK-3475) in combination with lenvatinib (MK-7902) per tumor cohort based on Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) by investigator assessments in initial cohorts, and by blinded independent central review (BICR) in cohorts that expand combining the initial and expansion cohorts (For participants with glioblastoma [GBM], response will be assessed based on Response Assessment in Neuro-Oncology [RANO] criteria) B) To assess safety and tolerability of treatment with pembrolizumab in combination with lenvatinib per tumor cohort assessed by the percentage of adverse events (AEs) ; Secondary Objective: A) To evaluate disease control rate (DCR), duration of response (DOR) and progression-free survival (PFS) of pembrolizumab in combination with lenvatinib per tumor cohort based on RECIST 1.1 by investigator assessments in initial cohorts, and by BICR in cohorts that expand combining the initial and expansion cohorts B) To evaluate overall survival (OS) of pembrolizumab in combination with lenvatinib per tumor cohort C) To characterize the population pharmacokinetics (PK) of lenvatinib when co-administered with pembrolizumab in participants per tumor cohort ; Primary end point(s): 1. Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) criteria for glioblastoma (GBM) by investigator assessment in initial cohorts 2. ORR per RECIST 1.1 or RANO by blinded independent central review (BICR) in expanded cohorts 3. Percentage of participants who experience an adverse event (AE) 4. Percentage of participants who discontinue study treatment due to an AE ; Timepoint(s) of evaluation of t | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Disease Control Rate (DCR) per RECIST 1.1 by investigator assessment in initial cohorts 2. Duration of Response (DOR) per RECIST 1.1 or RANO (GBM) by investigator assessment in initial cohorts 3. Progression Free Survival (PFS) per RECIST 1.1 or RANO (GBM) by investigator assessment in initial cohorts 4. Overall Survival (OS) in initial cohorts 5. DCR per RECIST 1.1 by BICR in expanded cohorts 6. DOR per RECIST 1.1 or RANO (GBM) by BICR in expanded cohorts 7. PFS per RECIST 1.1 or RANO (GBM) by BICR in expanded cohorts 8. OS in expanded cohorts 9. Plasma concentration of lenvatinib ; Timepoint(s) of evaluation of this end point: 1. Up to 18 months 2. Up to 18 months 3. Up to 18 months 4. Up to 18 months 5. Up to 36 months 6. Up to 36 months 7. Up to 36 months 8. Up to 36 months 9. Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose and 2-12 hours post-dose; Cycle 2 Day 1: pre-dose, 0.5-4 hours, and 6-10 hours post-dose. Each cycle is 21 days | — |
Countries
Australia, Canada, Chile, France, Germany, Israel, Korea, Republic of, Spain, United Kingdom, United States
Contacts
Public ContactKevin G. Norwood
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Outcome results
None listed