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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02861573




Registration number
NCT02861573
Ethics application status
Date submitted
3/08/2016
Date registered
10/08/2016

Titles & IDs
Public title
Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365)
Scientific title
Phase Ib/II Trial of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (mCRPC) (KEYNOTE-365)
Secondary ID [1] 0 0
KEYNOTE-365
Secondary ID [2] 0 0
3475-365
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Castration-Resistant Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Pembrolizumab 200 mg
Treatment: Drugs - Olaparib 400 mg
Treatment: Drugs - Docetaxel 75 mg/m^2
Treatment: Drugs - Prednisone 5 mg
Treatment: Drugs - Enzalutamide 160 mg
Other interventions - Dexamethasone 8 mg
Treatment: Drugs - Olaparib 300 mg
Treatment: Drugs - Abiraterone acetate 1000 mg
Treatment: Drugs - Lenvatinib
Treatment: Other - Pembrolizumab/Vibostolimab coformulation
Treatment: Drugs - Carboplatin
Treatment: Drugs - Etoposide
Treatment: Other - Belzutifan 120mg

Experimental: Pembrolizumab+Olaparib - Participants with adenocarcinoma (AC) mCRPC in Cohort A will receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week dosing cycle (Q3W) and olaparib 400 mg capsules or 300 mg tablets by mouth (PO) twice a day (BID) continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue until progression or a maximum of 35 treatment cycles (up to 2 years). Treatment with olaparib will continue until progression. Participants who must discontinue 1 of the 2 drugs in the combination due to adverse events may continue the study with the other combination drug.

Experimental: Pembrolizumab+Docetaxel+Prednisone - Participants with AC mCRPC in Cohort B will receive pembrolizumab 200 mg IV on Day 1 Q3W, docetaxel 75 mg/m\^2 IV on Day 1 Q3W, and prednisone 5 mg tablet PO BID continuously from Day 1 of Cycle 1. Participants will only be permitted to receive a maximum of 10 cycles of docetaxel and prednisone. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug.

Experimental: Pembrolizumab+Enzalutamide - Participants with AC mCRPC in Cohort C will receive pembrolizumab 200 mg IV on Day 1 Q3W and enzalutamide 160 mg PO every day (QD) continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue until progression or a maximum of 35 treatment cycles (up to 2 years). Treatment with enzalutamide will continue until progression. Participants who must discontinue 1 of the 2 drugs in the combination due to adverse events may continue the study with the other combination drug.

Experimental: Pembrolizumab+Abiraterone+Prednisone - Participants with AC mCRPC in Cohort D will receive pembrolizumab 200 mg IV on Day 1 Q3W, abiraterone acetate 1000 mg PO QD and prednisone 5 mg tablet PO BID continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug.

Experimental: Pembrolizumab+Lenvatinib: AC - Participants with AC mCRPC in Cohort E will receive pembrolizumab 200 mg IV on Day 1 Q3W, and lenvatinib 20 mg PO QD continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug.

Experimental: Pembrolizumab+Lenvatinib:t-NE - Participants with neuroendocrine (t-NE) mCRPC in Cohort F will receive pembrolizumab 200 mg IV on Day 1 Q3W, and lenvatinib 20 mg PO QD continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug.

Experimental: Pembrolizumab/Vibostolimab coformulation - Participants with AC mCRPC in Cohort G will receive a coformulation fixed dose combination of 200 mg pembrolizumab and 200 mg vibostolimab (MK-7684) Q3W IV from Day 1 of Cycle 1. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression.

Experimental: Pembrolizumab/Vibostolimab coformulation:t-NE - Participants with t-NE mCRPC in Cohort H will receive a coformulation fixed dose combination of 200 mg pembrolizumab and 200 mg vibostolimab (MK-7684) Q3W IV from Day 1 of Cycle 1. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression.

Experimental: Pembrolizumab+Carboplatin+Etoposide - Participants with neuroendocrine mCRPC in Cohort I Arm 1 will receive pembrolizumab 200 mg IV on Day 1 Q3W + carboplatin titrated to an area under the plasma drug concentration-time curve \[AUC\] 5 IV on Day 1 Q3W + etoposide 100 mg/m\^2 IV on Days 1, 2, and 3 Q3W. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Treatment with carboplatin+etoposide will continue for a maximum of 4 cycles (up to 2.8 months). Participants who must discontinue 1 or 2 of the 3 drugs due to adverse events in the combination may continue the study with the other combination drug/drugs.

Experimental: Carboplatin+Etoposide - Participants with neuroendocrine mCRPC in Cohort I Arm 2 will receive carboplatin titrated to an area under the plasma drug concentration-time curve \[AUC\] 5 IV on Day 1 Q3W + etoposide 100 mg/m\^2 IV on Days 1, 2, and 3 Q3W. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression. Treatment with carboplatin+etoposide will continue for a maximum of 4 cycles (up to 2.8 months). Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug.

Experimental: Belzutifan - Participants with AC mCRPC in Cohort J will receive belzutifan 120mg QD in the initial cohort. If an efficacy signal is detected in this arm based on a totality of evidence, Cohort J may be expanded further where participants will be randomized 1:1 to receive either belzutifan 120 mg QD or belzutifan 120 mg QD and pembrolizumab 200 mg Q3W. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression.

Experimental: Pembrolizumab+Belzutifan - Participants with AC mCRPC in Cohort J will receive belzutifan 120mg QD in the initial cohort. If an efficacy signal is detected in this arm based on a totality of evidence, Cohort J may be expanded further where participants will be randomized 1:1 to receive either belzutifan 120 mg QD or belzutifan 120 mg QD and pembrolizumab 200 mg Q3W. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression.


Treatment: Other: Pembrolizumab 200 mg
IV Q3W

Treatment: Drugs: Olaparib 400 mg
Eight 50-mg capsules PO BID

Treatment: Drugs: Docetaxel 75 mg/m^2
IV Q3W

Treatment: Drugs: Prednisone 5 mg
One 5-mg tablet PO BID

Treatment: Drugs: Enzalutamide 160 mg
Four 40-mg capsules, four 40-mg tablets, or two 80-mg tablets PO QD

Other interventions: Dexamethasone 8 mg
Premedication for Cohort B given PO at 12, 3, and 1 hours prior to docetaxel infusion Q3W

Treatment: Drugs: Olaparib 300 mg
Two 150-mg tablets PO BID

Treatment: Drugs: Abiraterone acetate 1000 mg
Two 500-mg or four 250-mg tablets PO QD

Treatment: Drugs: Lenvatinib
20 mg PO QD

Treatment: Other: Pembrolizumab/Vibostolimab coformulation
IV Q3W

Treatment: Drugs: Carboplatin
IV Q3W

Treatment: Drugs: Etoposide
IV on Days 1, 2 and 3 of each cycle

Treatment: Other: Belzutifan 120mg
PO QD
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With a Decrease of =50% in Prostatic Specific Antigen (PSA)
Timepoint [1] 0 0
From Baseline Measured Every 3 Weeks Until Radiographic Progression Estimated to be Approximately 2 Years
Primary outcome [2] 0 0
Number of Participants with Adverse Events (AEs)
Timepoint [2] 0 0
Assessed Every 3 Weeks Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Primary outcome [3] 0 0
Number of Participants Discontinuing Study Drug Due to AEs
Timepoint [3] 0 0
Assessed Every 3 Weeks Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Primary outcome [4] 0 0
Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed by Blinded Independent Central Review (BICR)
Timepoint [4] 0 0
Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Secondary outcome [1] 0 0
Disease Control Rate (DCR) Based on Prostate Cancer Working Group 3 (PCWG3)-modified RECIST 1.1 Assessed by BICR
Timepoint [1] 0 0
Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Secondary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Secondary outcome [3] 0 0
Duration of Response (DOR) Based on PCWG3-modified RECIST 1.1 Assessed by BICR
Timepoint [3] 0 0
Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Secondary outcome [4] 0 0
ORR Based on PCWG3-modified RECIST 1.1 Assessed by BICR
Timepoint [4] 0 0
Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Secondary outcome [5] 0 0
Time to PSA Progression
Timepoint [5] 0 0
Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Secondary outcome [6] 0 0
Radiographic Progression-free Survival (rPFS) Based on PCWG3-modified RECIST 1.1 Assessed by BICR
Timepoint [6] 0 0
Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Secondary outcome [7] 0 0
Composite Response Rate Defined as Any One of the Following: A. Response Based on RECIST 1.1; B. PSA Decrease of =50%; or C. Circulating Tumor-cell Count Conversion (Pembrolizumab + Olaparib Cohort Only)
Timepoint [7] 0 0
Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years

Eligibility
Key inclusion criteria
* For Cohorts A, B, C, D, E, G, J: Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology

* For Cohorts F, H, I: Has t-NE or de novo metastatic prostate cancer defined by =1% neuroendocrine cells that are located in discrete regions of a recent biopsy specimen from a metastasis as determined by the investigational site and confirmed by central histology review prior to enrollment. Epstein criteria of neuroendocrine differentiation in prostate cancer is used for eligibility. Specimens must have one of the morphologies of Small cell carcinoma or Large cell neuroendocrine carcinoma (LCNEC) or Mixed (small or large cell) NE carcinoma - acinar adenocarcinoma with positive IHC confirmed by central pathology review
* Is able to provide tumor tissue from a site not previously irradiated as follows: Cohorts A, E, G and J: must provide a core or excisional biopsy from soft tissue or bone biopsy within 1 year of screening and after developing mCRPC; Cohort B: must provide an archival tumor tissue sample or tumor tissue from a newly obtained core or excisional biopsy from soft tissue if the lesion is clinically accessible; Cohorts C and D with soft tissue disease: must provide a core or excisional biopsy from a soft tissue lesion if clinically accessible within 1 year of screening and after developing mCRPC and an archival specimen if available; and Cohorts F, H, and I must provide a core or excisional biopsy from soft tissue or a bone biopsy. For de novo metastatic neuroendocrine prostate participants, biopsies must be performed within 1 year of screening. Participants with bone metastasis only must provide an archival tumor tissue specimen
* Has prostate cancer progression within 6 months prior to screening, as determined by the investigator, by means of one of the following: PSA progression as defined by a minimum of 2 rising PSA levels with an interval of =1 week between each assessment where the PSA value at screening should be =2 ng/mL; radiographic disease progression in soft tissue based on Response Evaluation Criteria In Solid Tumors Version 1.1 criteria with or without PSA progression; radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scan with or without PSA progression. Participants with de novo neuroendocrine prostate cancer will not need to provide evidence of progression within 6 months
* Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<2.0 nM). Treatment with luteinizing hormone-releasing hormone agonists or antagonists for all cohorts must have been initiated =4 weeks prior to first dose of study therapy and must be continued throughout the study. Participants with de novo metastatic NE prostate cancer will not be required to have been previously treated with androgen deprivation therapy (ADT). ADT must be started in these participants by the time of treatment allocation/randomization
* Participants receiving bone resorptive therapy (including, but not limited to bisphosphonate or receptor activator of nuclear factor kappa-ß ligand inhibitor) must be on stable doses for =4 weeks prior to first dose of study therapy
* Must be abstinent from heterosexual intercourse, refrain from donating sperm, or agree to use contraception (unless confirmed to be azoospermic) during the intervention period starting with the first dose of study therapy. The length of time required to continue contraception after the last dose of study intervention for each study intervention is as follows: 7 days for abiraterone acetate and lenvatinib; 30 days for enzalutamide; and 95 days for olaparib, docetaxel, and carboplatin/etoposide. No contraception measures are required during and after the intervention period for pembrolizumab/vibostolimab coformulation
* Has a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale for Cohorts A and C and a performance status of 0 or 1 for Cohorts B, D, E, F, G, H, I and J within 10 days of study start
* For Cohort A: Has received docetaxel for mCRPC. Prior treatment with 1 other chemotherapy for mCRPC is allowed. Up to 2 second-generation hormonal manipulations (e.g., abiraterone acetate and/or enzalutamide) are allowed. Prior docetaxel for metastatic hormone-sensitive prostate cancer is allowed if =4 weeks have elapsed from the last dose of docetaxel prior to day 1 of Cycle 1
* For Cohort B: Has received prior treatment with either abiraterone acetate or enzalutamide (but not both) in the prechemotherapy mCRPC state. Participants in Cohort B must have received at least 4 weeks of either abiraterone or enzalutamide treatment (but not both) who failed treatment or became intolerant of the drug
* For Cohort C: Has received prior treatment with abiraterone acetate in the pre-chemotherapy mCRPC state without prior enzalutamide. Participants in Cohort C must have received at least 4 weeks of abiraterone treatment who failed treatment or become intolerant of the drug. Participants who received abiraterone acetate in the hormone-sensitive state will not be eligible
* For Cohort D: Has not received chemotherapy for mCRPC and has either not had prior second generation hormonal manipulation for mCRPC OR has previously been treated with enzalutamide for mCRPC and failed treatment or has become intolerant of the drug. Prior docetaxel for metastatic hormone-sensitive prostate cancer is allowed if =4 weeks have elapsed from the last dose of docetaxel. Prior treatment with abiraterone acetate in the hormone-sensitive metastatic setting is allowed as long as there was no progression on this agent and abiraterone acetate was not discontinued due to adverse events (AEs)
* For Cohorts E, G and J: Has received docetaxel for mCRPC. Prior treatment with 1 other chemotherapy for mCRPC is allowed. Up to 2 second-generation hormonal manipulations (eg, abiraterone acetate, enzalutamide, apalutamide, darolutamide or other next-generation hormonal agents [NHA]) are allowed. Participants who received prior ketoconazole for metastatic disease may be enrolled. If docetaxel chemotherapy is used more than once (eg, once for metastatic hormone-sensitive and once for mCRPC), it will be considered as 1 therapy. Prior docetaxel for metastatic hormone-sensitive prostate cancer (mHSPC) is allowed if =4 weeks have elapsed from the last dose of docetaxel prior to Day 1 of Cycle 1
* For Cohort F, H, and I: Participants must have received prior treatment with androgen deprivation therapy (ADT) for metastatic disease. Prior treatment with up to a total of 2 chemotherapies for mCRPC is allowed, as well as up to 2 second-generation hormonal manipulations for mCRPC. Participants who received prior ketoconazole for metastatic disease may be enrolled. Docetaxel for mHSPC is allowed in addition to docetaxel for mCRPC. If docetaxel chemotherapy is used more than once (eg, once for metastatic hormone-sensitive and once for mCRPC), it will be considered as 1 therapy
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
* Has had a prior anticancer monoclonal antibody (mAb) within 4 weeks prior to first dose study therapy or who has not recovered (i.e., Grade =1 or at baseline) from AEs due to mAbs administered >4 weeks earlier
* Has had prior chemotherapy, targeted small molecule therapy abiraterone treatment, enzalutamide treatment, or radiation therapy within 2 weeks prior to first dose of study therapy or who has not recovered (ie, Grade =1 or at baseline) from AEs due to a previously administered agent
* Is currently participating in and receiving study therapy or has participated in a study of an investigational agent and received study drug or used an investigational device within 4 weeks of treatment allocation/randomization
* Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to treatment allocation/randomization
* Has had prior treatment with therapeutic radiopharmaceuticals for prostate cancer, such as Radium-223 or Leutitium-177, within 4 weeks prior to the first dose of trial treatment
* Has an active autoimmune disease that has required systemic treatment in past 2 years
* Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease
* Has previously participated in any other pembrolizumab trial, or received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), and anti-programmed cell death ligand 1 (anti-PD-L2)
* Has a known history of Human Immunodeficiency Virus (HIV)
* Has known active Hepatitis B or Hepatitis C
* Has received a live vaccine or live-attenuated vaccine within 30 days of the first dose of study therapy
* Has known active central nervous system metastases and/or carcinomatous meningitis
* Has a "superscan" bone scan defined as an intense symmetric activity in the bones and diminished renal parenchymal activity on baseline bone scan such that the presence of additional metastases in the future could not be evaluated
* Has had prior solid, organ or bone marrow transplant
* For Cohort A: Has experienced a seizure or seizures within 6 months of study start or is currently being treated with cytochrome P450 enzyme (CYP) inducing anti-epileptic drugs for seizures
* For Cohort A: Is currently receiving strong or moderate inhibitors of CYP3A4 including azole antifungals; macrolide antibiotics; or protease inhibitors
* For Cohort A: Is currently receiving strong or moderate inducers of CYP3A4
* For Cohort A: Has myelodysplastic syndrome
* For Cohort A: Has symptomatic congestive heart failure (New York Heart Association Class III or IV heart disease), unstable angina pectoris, cardiac arrhythmia, or uncontrolled hypertension
* For Cohort B: Has received prior treatment with docetaxel or another chemotherapy agent for metastatic prostate cancer
* For Cohort B: Has peripheral neuropathy Common Terminology Criteria for Adverse Events =2 except due to trauma
* For Cohort B: Has ascites and/or clinically significant pleural effusion
* For Cohort B:Has symptomatic congestive heart failure (New York Heart Association Class III or IV heart disease)
* For Cohort B: Is currently receiving any of the following classes of inhibitors of CYP3A4: azole antifungals; macrolide antibiotics; or protease inhibitors
* For Cohort C: Has received prior chemotherapy for mCRPC. Prior docetaxel for metastatic hormone-sensitive prostate cancer is allowed if =4 weeks elapsed from last dose of docetaxel. Participants who received abiraterone acetate in the hormone-sensitive state will not be eligible
* For Cohort C: Has a history of seizure or any condition that may predispose to seizure (including, but not limited to prior cerebrovascular accident, transient ischemic attack, or brain arteriovenous malformation; or intracranial masses such as a schwannoma or meningioma that is causing edema or mass effect)
* For Cohort C:Has known or suspected brain metastasis or leptomeningeal carcinomatosis
* For Cohort C: Has a history of loss of consciousness within 12 months of the screening visit
* For Cohort C: Has hypotension (systolic blood pressure <86 millimeters of mercury [mmHg]) or uncontrolled hypertension (systolic blood pressure >170 mmHg or diastolic blood pressure >105 mmHg) at the screening visit
* For Cohort C: Has received treatment with 5-a reductase inhibitors (e.g., finasteride, dutasteride), estrogens, and/or cyproterone within 4 weeks prior to Cycle 1
* For Cohort C: Has a history of prostate cancer progression on ketoconazole
* For Cohort D: Has received prior treatment with docetaxel or another chemotherapy agent for metastatic prostate cancer
* For Cohort D: Has progressed on prior abiraterone acetate for treatment of castration sensitive or resistant metastatic prostate cancer
* For Cohort D: Has discontinued prior treatment with abiraterone acetate due to AEs
* For Cohort D: Has previously been treated with ketoconazole for prostate cancer for >7 days
* For Cohort D: Has received prior systemic treatment with an azole drug (eg, fluconazole, itraconazole) within 4 weeks of Cycle 1, Day 1
* For Cohort D: Has uncontrolled hypertension (systolic BP = 160 mm Hg or diastolic BP = 95 mm Hg)
* For Cohort D: Has a history of pituitary or adrenal dysfunction
* For Cohort D: Has clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association Class II-IV heart disease or cardiac ejection fraction measurement of <50% at baseline
* For Cohort D: Has atrial fibrillation, or other cardiac arrhythmia requiring therapy
* For Cohort D: Has a history of chronic liver disease
* For Cohort D: Is currently receiving strong CYP3A4 inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) during abiraterone acetate treatment, CYP2D6 substrates with a narrow therapeutic index (for example thioridazine), or CYP2C8 substrates with a narrow therapeutic index (for example pioglitazone)
* For Cohorts E and F: Has a left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range, as determined by multigated acquisition (MUGA) or echocardiogram (ECHO)
* For Cohorts E and F: Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
* For Cohorts E and F: Has prolongation of QT interval by Fredericia (QTcF) interval to >480 milliseconds
* For Cohorts E and F: Has had major surgery within 3 weeks prior to first dose of study interventions
* For Cohorts E and F: Has pre-existing =Grade 3 gastrointestinal or non-gastrointestinal fistula
* For Cohorts E and F: Has had significant cardiovascular impairment within 12 months of the first dose of study intervention, such as history of New York Heart Association >Class II congestive heart failure, unstable angina, myocardial infarction, or cerebrovascular accident (CVA)/stroke, cardiac revascularization procedure, or cardiac arrhythmia associated with hemodynamic instability
* For Cohorts E and F: Has active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of lenvatinib
* For Cohorts E and F: Has gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib
* For Cohorts G, H, and I: Has had a severe hypersensitivity reaction to treatment with another monoclonal antibody
* For Cohorts G, H, and I: Has symptomatic ascites or pleural effusion
* For Cohort I: Has clinically active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, and/or abdominal carcinomatosis
* For Cohort I: Has received previous treatment for prostate cancer with platinum-containing compounds

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/11/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
22/10/2027
Actual
Sample size
Target
1200
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
MSD Australia - North Ryde
Recruitment postcode(s) [1] 0 0
- North Ryde
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Oregon
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
South Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
Canada
State/province [11] 0 0
Quebec
Country [12] 0 0
Denmark
State/province [12] 0 0
Glostrup
Country [13] 0 0
Finland
State/province [13] 0 0
Espoo
Country [14] 0 0
France
State/province [14] 0 0
Paris
Country [15] 0 0
Germany
State/province [15] 0 0
Haar
Country [16] 0 0
Ireland
State/province [16] 0 0
Dublin
Country [17] 0 0
Italy
State/province [17] 0 0
Rome
Country [18] 0 0
Mexico
State/province [18] 0 0
Mexico City
Country [19] 0 0
Netherlands
State/province [19] 0 0
Haarlem
Country [20] 0 0
New Zealand
State/province [20] 0 0
Auckland
Country [21] 0 0
Poland
State/province [21] 0 0
Warsaw
Country [22] 0 0
Spain
State/province [22] 0 0
Madrid
Country [23] 0 0
Sweden
State/province [23] 0 0
Stockholm
Country [24] 0 0
Taiwan
State/province [24] 0 0
Taipei
Country [25] 0 0
Turkey
State/province [25] 0 0
Istanbul
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Hoddesdon

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Trialsites@msd.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pd
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://engagezone.msd.com/ds_documentation.php


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents



Results not provided in https://clinicaltrials.gov/study/NCT02861573