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

This study is currently recruiting participants.
Verified April 2014 by Merck Sharp & Dohme Corp.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01848834
First received: May 3, 2013
Last updated: April 21, 2014
Last verified: April 2014

May 3, 2013
April 21, 2014
May 2013
June 2015   (final data collection date for primary outcome measure)
  • 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 Teatment 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 ]
  • Number of participants experiencing adverse events [ Time Frame: From first dose 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: From first dose up to last dose of study treatment (up to 2 years) ] [ Designated as safety issue: Yes ]
  • Number of participants with TNBC, head and neck, or urothelial cancer who achieve a clinically meaningful overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria [ Time Frame: Baseline and every 8 weeks, up to 2 years ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01848834 on ClinicalTrials.gov Archive Site
  • 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 Radioloogy 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 ]
  • Number of participants with head and neck cancer and who are human papilloma virus (HPV)-positive who achieve a clinically meaningful ORR per RECIST 1.1 criteria [ Time Frame: Baseline and every 8 weeks, up to 2 years ] [ Designated as safety issue: No ]
  • Number of participants with log fold change from baseline in cytokines >1 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
  • Number of participants with TNBC, head and neck, or urothelial cancer who achieve a clinically meaningful ORR per immune-related response criteria (irRC) [ Time Frame: Baseline and every 8 weeks, up to 2 years ] [ Designated as safety issue: No ]
Number of participants with log fold change from baseline in cytokines >1 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
Not Provided
 
Study of MK-3475 in Participants With Advanced Solid Tumors (MK-3475-012/KEYNOTE-012)
A Phase Ib Multi-Cohort Study of MK-3475 in Subjects With Advanced Solid Tumors

This study is being done to investigate the safety, tolerability and anti-tumor activity of 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)

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

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Cancer
  • Solid Tumor
Drug: MK-3475
  • Experimental: Cohort A - Triple negative breast cancer
    Participants will receive MK-3475, 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)
    Intervention: Drug: MK-3475
  • Experimental: Cohort B - Head/neck cancer
    Participants will receive MK-3475, 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)
    Intervention: Drug: MK-3475
  • Experimental: Cohort C - Urothelial tract cancer
    Participants will receive MK-3475, 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)
    Intervention: Drug: MK-3475
  • Experimental: Cohort D - Gastric cancer
    Participants will receive MK-3475, 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)
    Intervention: Drug: MK-3475
  • Experimental: Cohort B2 - Head/neck cancer
    Participants will receive MK-3475, 200 mg/kg, 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)
    Intervention: Drug: MK-3475
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
224
June 2015
June 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Toll Free Number 1-888-577-8839
United States,   Belgium,   Israel,   Japan,   Korea, Republic of
 
NCT01848834
3475-012, 2012-005771-14, 142453
No
Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Not Provided
Not Provided
Merck Sharp & Dohme Corp.
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP