Study of Pembrolizumab (MK-3475) in Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC)(MK-3475-199/KEYNOTE-199)

NCT02787005 | Completed Phase 2 Results FDA Drug

• 5 other identifiers: 3475-199163366MK-3475-199KEYNOTE-1992015-003644-40
• Study Type: interventional
• Target: 388
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a study of pembrolizumab (MK-3475) in participants with metastatic castration-resistant prostate cancer (mCRPC). Participants will be enrolled into one of five cohorts: Cohort 1 (participants with programmed cell death ligand 1 \[PD-L1\]-positive, measurable disease), Cohort 2 (participants with PD-L1 negative, measurable disease), Cohort 3 (participants with bone-metastases and non-measurable disease) post-chemotherapy, Cohort 4 (participants with Response Evaluation Criteria in Solid Tumors version 1.1- \[RECIST 1.1\]-measureable disease) and Cohort 5 (participants with bone metastases only or bone-predominant disease) pre-chemotherapy.

Conditions

Metastatic Castration-resistant Prostate Cancer

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Cell Death 1 Ligand 1(PDL1, PD-L1); Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined)

  ORR was defined as the percentage of participants who experienced a complete response (CR; disappearance of all target lesions) or a partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 by central imaging vendor. Per protocol, analysis for this outcome measure was conducted in Cohorts 1 and 2 combined, as well as in Cohorts 1, 2, and 4 separately for the first course of treatment.

  Up to ~52 months

Secondary Outcomes (13)

• Percentage of Participants Who Experienced an Adverse Event (AE)

  Up to ~52 months

• Percentage of Participants Who Discontinued Study Treatment Due to an AE

  Up to ~52 months

• Disease Control Rate (DCR) (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, Cohorts 4 and 5 Combined)

  Up to ~52 months

• Duration of Response (DOR) Per PCWG3-modified RECIST 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined)

  Up to ~52 months

• DOR- Per RECIST 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined)

  Up to ~52 months

Study Arms (5)

Cohort 1: PD-L1 positive with measurable disease

EXPERIMENTAL

Participants with programmed cell death ligand 1 (PD-L1)-positive, measurable disease receive pembrolizumab 200 mg via intravenous infusion on Day 1 of every 3-week cycle for up to 2 years.

Biological: Pembrolizumab

Cohort 2: PD-L1 negative with measurable disease

EXPERIMENTAL

Participants with PD-L1 negative, measurable disease receive pembrolizumab 200 mg via intravenous infusion on Day 1 of every 3-week cycle for up to 2 years.

Biological: Pembrolizumab

Cohort 3: Bone metastases with non-measurable disease

EXPERIMENTAL

Participants with bone metastases and non-measurable disease receive pembrolizumab 200 mg via intravenous infusion on Day 1 of every 3-week cycle for up to 2 years.

Biological: Pembrolizumab

Cohort 4: RECIST 1.1-measureable disease

EXPERIMENTAL

Participants with Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)-measureable disease receive pembrolizumab 200 mg via intravenous infusion on Day 1 of every 3-week cycle for up to 2 years.

Biological: Pembrolizumab

Cohort 5: Bone metastases only or bone-predominant disease

EXPERIMENTAL

Participants with bone metastases only or bone-predominant disease receive pembrolizumab 200 mg via intravenous infusion on Day 1 of every 3-week cycle for up to 2 years.

Biological: Pembrolizumab

Interventions

Pembrolizumab BIOLOGICAL

Intravenous infusion

Also known as: MK-3475, KEYTRUDA®

Cohort 1: PD-L1 positive with measurable disease; Cohort 2: PD-L1 negative with measurable disease; Cohort 3: Bone metastases with non-measurable disease; Cohort 4: RECIST 1.1-measureable disease; Cohort 5: Bone metastases only or bone-predominant disease

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology. Disease must be either metastatic or locally confined inoperable disease that cannot be treated with definitive intent (no chance for a curative intervention).
• Has supplied tumor tissue from a newly obtained biopsy or a biopsy obtained ≤12 months prior to study start and an archival specimen, if available, from a site not previously irradiated. Participants in Cohorts 1, 2, and 4 with visceral/measurable lesions must provide a newly obtained biopsy performed after the last line of systemic therapy or a biopsy obtained ≤12 months prior to study start and an archival specimen, if available. Participants in Cohorts 3 and 5 must at least provide an archival specimen.
• For Cohorts 1, 2, and 3 only:
• Has been treated with:
• At least 1 targeted endocrine therapy (defined as second generation antiandrogen therapies that include but are not limited to abiraterone acetate with prednisone, enzalutamide, and next generation targeted agents such as ARN-509).
• At least 1 regimen/line of chemotherapy that contained docetaxel.
• No more than 2 chemotherapy regimens.
• No more than 3 regimens/lines of the aforementioned treatments (having failed/progressed on chemotherapy and targeted endocrine therapy).
• For Cohorts 4 and 5 only:
• Failing or showing early signs of failure on current pre-chemotherapy enzalutamide treatment as defined by Prostate Cancer Working Group 3 (PCWG3) guidelines. Participants can have failed prior abiraterone treatment before current enzalutamide treatment. Participants must have had a clinically meaningful response to enzalutamide treatment. Enzalutamide must have been initiated no less than 4 weeks prior to the first dose of trial treatment and be continued throughout the study.
• For All Cohorts:
• Has documented prostate cancer progression within 6 months prior to screening, as determined by the Investigator, by means of one of the following: 1) PSA progression as defined by a minimum of 3 rising PSA levels with an interval of ≥1 week between each assessment where the PSA value at screening should be ≥2 ng/mL, OR, 2) Radiographic disease progression in soft tissue or bone with or without PSA progression
• Has ongoing androgen deprivation with total serum testosterone \<50 ng/dL (\<2.0 nM).
• Participants receiving bone resorptive therapy (including but not limited to bisphosphonate or Receptor activator of nuclear factor kappa-B ligand \[RANK-L inhibitor\]) must have been on stable doses for ≥4 weeks prior to first dose of study drug.
• Has a performance status of 0, 1 or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale

You may not qualify if:

• For All Cohorts:
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of study drug.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the first dose of study drug or who has not recovered (i.e., ≤ Grade 1 or at Baseline) from AEs due to mAbs administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or external beam radiation therapy within 4 weeks prior to the first dose of study drug or who has not recovered (i.e., ≤ Grade 1 or at Baseline) from AEs due to a previously administered agent.
• Has a known additional malignancy that has had progression or has required active treatment in the last 3 years. Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that has undergone potentially curative therapy.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• Has evidence of interstitial lung disease and/or a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Has previously participated in any other pembrolizumab (MK-3475) trial, or received prior therapy with an anti-programmed cell death 1 (anti-PD-1, anti-PD ligand 1 \[anti-PD-L1\], and anti-PD-L2 \[including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways\]).
• Has a known history of Human Immunodeficiency Virus (HIV).
• Has known active Hepatitis B or Hepatitis C.
• Has received a live vaccine within 30 days of planned start of study drug. Any licensed coronavirus disease 2019 (COVID-19) vaccine (including for Emergency use) in a particular country is allowed in the study as long as they are messenger ribonucleic acid (mRNA) vaccines, adenoviral vaccines, or inactivated vaccines. Investigational vaccines (ie, those not licensed or approved for Emergency Use) are not allowed.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (3)

• Antonarakis ES, Piulats JM, Gross-Goupil M, Goh J, Ojamaa K, Hoimes CJ, Vaishampayan U, Berger R, Sezer A, Alanko T, de Wit R, Li C, Omlin A, Procopio G, Fukasawa S, Tabata KI, Park SH, Feyerabend S, Drake CG, Wu H, Qiu P, Kim J, Poehlein C, de Bono JS. Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study. J Clin Oncol. 2020 Feb 10;38(5):395-405. doi: 10.1200/JCO.19.01638. Epub 2019 Nov 27.

  PMID: 31774688 RESULT

• Graff JN, Hoimes CJ, Gerritsen WR, Vaishampayan UN, Elliott T, Hwang C, Ten Tije AJ, Omlin A, McDermott RS, Fradet Y, Tagawa ST, Kilari D, Ferrario C, Uemura H, Jones RJ, Fukasawa S, Peer A, Niu C, Poehlein CH, Qiu P, Suttner L, de Wit R, Schloss C, de Bono JS, Antonarakis ES. Pembrolizumab plus enzalutamide for metastatic castration-resistant prostate cancer progressing on enzalutamide: cohorts 4 and 5 of the phase 2 KEYNOTE-199 study. Prostate Cancer Prostatic Dis. 2025 Jun;28(2):411-418. doi: 10.1038/s41391-024-00865-5. Epub 2024 Aug 12.

  PMID: 39134652 RESULT

• Cristescu R, Aurora-Garg D, Albright A, Xu L, Liu XQ, Loboda A, Lang L, Jin F, Rubin EH, Snyder A, Lunceford J. Tumor mutational burden predicts the efficacy of pembrolizumab monotherapy: a pan-tumor retrospective analysis of participants with advanced solid tumors. J Immunother Cancer. 2022 Jan;10(1):e003091. doi: 10.1136/jitc-2021-003091.

  PMID: 35101941 DERIVED

Related Links

• Merck Oncology Clinical Trials Information

MeSH Terms

Conditions

Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2016
• First Posted: June 1, 2016
• Study Start: July 1, 2016
• Primary Completion: February 28, 2022
• Study Completion: February 28, 2022
• Last Updated: November 21, 2024
• Results First Posted: March 24, 2023

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share