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Phase 2 Study of MK-3475 in Patients With Microsatellite Unstable (MSI) Tumors

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ClinicalTrials.gov Identifier: NCT01876511
Recruitment Status : Recruiting
First Posted : June 12, 2013
Last Update Posted : March 29, 2018
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

June 10, 2013
June 12, 2013
March 29, 2018
September 2013
June 2021   (Final data collection date for primary outcome measure)
  • Immune-related progression free survival (irPFS) rate at 20 weeks in patients with MSI positive and negative colorectal adenocarcinoma using immune related response criteria (irRC) [ Time Frame: 4 years ]
  • Objective response rate (irORR) at 20 weeks in patients with MSI positive and negative colorectal adenocarcinoma using immune related response criteria (irRC) [ Time Frame: 4 years ]
  • Immune-related progression free survival (irPFS) rate in patients with MSI positive non-colorectal adenocarcinoma using immune related response criteria (irRC) at 20 weeks [ Time Frame: 4 years ]
  • objective response rate in patients with MSI-negative cancer with a mutator phenotype using RECIST 1.1 criteria [ Time Frame: 4 years ]
  • Immune-related progression free survival (irPFS) rate at 20 weeks in patients with MSI positive and negative colorectal adenocarcinoma using immune related response criteria (irRC) [ Time Frame: 4 years ]
  • Objective response rate (irORR) at 20 weeks in patients with MSI positive and negative colorectal adenocarcinoma using immune related response criteria (irRC) [ Time Frame: 4 years ]
  • Immune-related progression free survival (irPFS) rate in patients with MSI positive non-colorectal adenocarcinoma using immune related response criteria (irRC) at 20 weeks [ Time Frame: 4 years ]
Complete list of historical versions of study NCT01876511 on ClinicalTrials.gov Archive Site
  • Overall survival [ Time Frame: 4 years ]
  • irPFS and PFS in patients with MSI positive and negative tumors at 28 weeks using irRC and RECIST 1.1 [ Time Frame: 4 years ]
  • Best overall response rate and disease control rate in patients with MSI positive and negative tumors [ Time Frame: 4 years ]
  • Number of participants experiencing immune-related toxicities (IRAEs) [ Time Frame: 4 years ]
  • Does MSI as a marker predict treatment response [ Time Frame: 4 years ]
  • Identify alternative markers of MSI status. This includes but is not limited to MLH 1, MSH 2, MSH 6, PMS2, BRAF pV600E, and TGFBR2. [ Time Frame: 4 years ]
  • Overall survival [ Time Frame: 4 years ]
  • irPFS and PFS in patients with MSI positive and negative tumors at 28 weeks using irRC and RECIST 1.1 [ Time Frame: 4 years ]
  • Best overall response rate and disease control rate in patients with MSI positive and negative tumors [ Time Frame: 4 years ]
  • Number of participants experiencing immune-related toxicities (IRAEs) [ Time Frame: Continuous ]
  • Does MSI as a marker predict treatment response [ Time Frame: 4 years ]
Not Provided
Not Provided
 
Phase 2 Study of MK-3475 in Patients With Microsatellite Unstable (MSI) Tumors
Phase 2 Study of MK-3475 in Patients With Microsatellite Unstable (MSI) Tumors
This study will be looking at whether MK-3475 (an antibody that blocks negative signals to T cells) is effective (anti-tumor activity) and safe in three different patient populations. These include: 1. patients with MSI positive colon cancer, 2. patients with MSI negative colon cancer 3. patients with other MSI positive cancers, and 4. patients with MSI negative cancer with a mutator phenotype.
Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • MSI Positive Colorectal Cancer
  • MSI Negative Colorectal Cancer
  • MSI Positive Non-Colorectal Cancers
  • High Tumor Mutation Burden
  • Drug: MK-3475
    MK-3475 10 mg/kg every 14 days
  • Drug: MK-3475
    MK-3475 200mg flat dose every 21 days
  • Experimental: MSI Positive Colorectal Cancer
    Intervention: Drug: MK-3475
  • Experimental: MSI Negative Colorectal Cancer
    Intervention: Drug: MK-3475
  • Experimental: MSI Positive Non-Colorectal Cancer
    Intervention: Drug: MK-3475
  • Experimental: MSI Negative with Mutator Phenotype
    Intervention: Drug: MK-3475

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
171
71
June 2021
June 2021   (Final data collection date for primary outcome measure)

Inclusion Criteria:

1. Arm 1 only: Patients with MSI positive colorectal cancer 2. Arm 2 only: Patients with MSI negative colorectal cancer 3. Arm 3 only: Patients with MSI positive non-colorectal cancer 4. Arm 4 only: patients with hypermutated MSI negative cancer 4. Have measurable disease 5. ECOG Performance Status of 0 to 1 6. Adequate organ function as defined by study-specified laboratory tests 7. Must use acceptable form of birth control through the study and for 28 days after final dose of study drug 8. Signed informed consent form 9. Willing and able to comply with study procedures 10. Agree to have a biopsy of their cancer 11. Patients with colon cancer must have received at least two prior cancer therapy regimens.

12. Patients with other cancer types must have received at least one prior cancer therapy 13. Progressive disease

Exclusion Criteria:

  1. Patients with uncontrolled intercurrent illness, including but not limited to ongoing or active infection, systematic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric condition that would limit compliance with study requirements. .
  2. Patients who have had chemotherapy or biological cancer therapy within 2 weeks prior to the first dose of study drug
  3. Patients who have had radiation within 2 weeks prior to the first dose of study drug
  4. Patients who have undergone major surgery within 4 weeks of dosing of investigational agent
  5. Patients who have received another investigational product or investigational device within 4 weeks prior to receiving study drug
  6. Patients who have received any of the following concomitant therapy: IL-2, interferon, or other non-study immunotherapy regimens, immunosuppressive agents, other investigational therapies or chronic use of systemic corticosteroids within one week prior to first dose of study drug
  7. Patients who have received a live vaccine within 4 weeks prior to or after any dose of MK-3475 (exception: inactivated flu vaccines)
  8. Patients who have received growth factors, including but not limited to granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin, etc. within 2 weeks of study drug administration
  9. Patient who have had prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, or anti-CTLA-4 antibodies
  10. Patients with history of any autoimmune disease:inflammatory bowel disease, (including ulcerative colitis and Crohn's Disease), rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus (SLE) autoimmune vasculitis, CNS or motor neuropathy considered to be of autoimmune origin.
  11. Patients who have known history of infection with HIV, hepatitis B, or hepatitis C
  12. Patients with evidence of interstitial lung disease
  13. Systemically active steroid use
  14. Patients on home oxygen
  15. Patients with oxygen saturation of <92% on room air by pulse oximetry
  16. Pregnant or lactating
  17. Conditions, including alcohol or drug dependence, or intercurrent illness that would affect the patient's ability to comply with study visits and procedures
  18. Patient with known active central nervous system metastases and/or carcinomatous meningitis.
  19. Patients with primary brain tumors.
  20. Requires any other form of systemic or localized antineoplastic therapy while on study
  21. Has any tissue or organ allograft
  22. Patients with history of allogeneic hematopoeitic stem cell transplant
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
United States
 
 
NCT01876511
J1365
MK-3475-016 ( Other Identifier: Merck )
NA_00085756 ( Other Identifier: JHMIRB )
Yes
Not Provided
Not Provided
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Merck Sharp & Dohme Corp.
Principal Investigator: Dung Le, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
March 2018

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