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Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-012/KEYNOTE-012)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01848834
First received: May 3, 2013
Last updated: November 6, 2014
Last verified: November 2014
  Purpose

This study is being done to investigate the safety, tolerability and anti-tumor activity of pembrolizumab (MK-3475) in participants with advanced triple negative breast cancer (TNBC) (Cohort A), advanced head and neck cancer (Cohorts B and B2), advanced urothelial cancer (Cohort C), or advanced gastric cancer (Cohort D)


Condition Intervention Phase
Cancer
Solid Tumor
Drug: Pembrolizumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase Ib Multi-Cohort Study of MK-3475 in Subjects With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Number of Participants Experiencing Adverse Events [ Time Frame: Up to 90 days after last dose of study treatment (up to 2 years) ] [ Designated as safety issue: Yes ]
  • Number of Participants Discontinuing from Study Treatment Due to Adverse Events [ Time Frame: Up to last dose of study treatment (up to 2 years) ] [ Designated as safety issue: Yes ]
  • Overall Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Response Rate in Cohorts A,B,C, and D by Central Radiology Assessment [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Overall RECIST 1.1 Response Rate by Investigator Assessment for PD-L1-negative Participants in Cohort B2 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall RECIST 1.1 Response Rate by Central Radiology Assessment in Participants with Human Papilloma Virus (HPV)-positive Head and Neck Cancer [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Overall RECIST 1.1 Response Rate by Central Radiology Assessment in Asia Pacific Participants with Gastric Cancer [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Overall RECIST 1.1 Response Rate by Investigator Assessment for Cohort B2 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Overall RECIST 1.1 Response Rate by Investigator Assessment for Participants in Cohorts A,B,C, and D [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Number of participants with log fold change from baseline in cytokines >1 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]

Estimated Enrollment: 224
Study Start Date: May 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort A - Triple negative breast cancer
Participants will receive pembrolizumab, 10 mg/kg, intravenously (IV) once every 2 weeks, and will continue to receive drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years)
Drug: Pembrolizumab
Experimental: Cohort B - Head/neck cancer
Participants will receive pembrolizumab, 10 mg/kg, intravenously (IV) once every 2 weeks, and will continue to receive drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years)
Drug: Pembrolizumab
Experimental: Cohort C - Urothelial tract cancer
Participants will receive pembrolizumab, 10 mg/kg, intravenously (IV) once every 2 weeks, and will continue to receive drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years)
Drug: Pembrolizumab
Experimental: Cohort D - Gastric cancer
Participants will receive pembrolizumab, 10 mg/kg, intravenously (IV) once every 2 weeks, and will continue to receive drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years)
Drug: Pembrolizumab
Experimental: Cohort B2 - Head/neck cancer
Participants will receive pembrolizumab, 200 mg, intravenously (IV) once every 3 weeks, and will continue to receive drug until disease progression, death, withdrawal of consent, Investigator decision, or end of study (up to 2 years)
Drug: Pembrolizumab

Detailed Description:

Amendment 2 of the protocol added a new study arm (Cohort B2) for participants with advanced head and neck cancer who will receive a lower dose of pembrolizumab (MK-3475) every three weeks (Q3W); participants with programmed cell death ligand 1 (PD-L1)-negative tumors will also be analyzed separately.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically-confirmed diagnosis of tumor that is recurrent, metastatic, or persistent:

    • For Cohort A - triple negative breast cancer (estrogen, progesterone, and human epidermal growth factor receptor 2 [HER2] negative)
    • For Cohort B - squamous cell carcinoma of the head and neck (including HPV-positive head and neck squamous cell cancer).
    • For Cohort C - urothelial tract cancer of the renal pelvis, ureter, bladder, or urethra (transitional cell or non-transitional cell histology)
    • For Cohort D - adenocarcinoma of the stomach or gastroesophageal junction
    • For Cohort B2 - squamous cell carcinoma of the head and neck (both HPV-positive and -negative head and neck squamous cell cancer)
  • Any number of prior treatment regimens
  • Measurable disease
  • Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1
  • Female participants of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study treatment
  • Male participants must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study treatment

Exclusion Criteria:

  • Currently participating in/has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study treatment
  • Diagnosis of immunosuppression or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
  • Anti-cancer monoclonal antibody treatment within 4 weeks prior to study Day 1 or not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Chemotherapy, targeted small molecule therapy or radiation therapy within 2 weeks prior to study Day 1 or not recovered from adverse events due to a previously administered agent
  • Known additional malignancy that is progressing or requires active treatment excepting basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
  • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Active autoimmune disease requiring systemic treatment within the past 3 months or documented history of clinically severe autoimmune disease, or syndrome that requires systemic steroids or immunosuppressive agents
  • Evidence of interstitial lung disease
  • Active infection requiring systemic therapy
  • Known psychiatric or substance abuse disorders
  • Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death 1 ligand 1(PD-L1), anti-PD-L2, anti-CD137 antibody, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody
  • Known history of human immunodeficiency virus (HIV)
  • Known active Hepatitis B or Hepatitis C
  • Received live vaccine within 30 days prior to start of study treatment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01848834     History of Changes
Other Study ID Numbers: 3475-012, 2012-005771-14, 142453
Study First Received: May 3, 2013
Last Updated: November 6, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on November 25, 2014