Clinical Trials /

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

NCT01876511

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 2 Study of MK-3475 in Patients With Microsatellite Unstable (MSI) Tumors
  • Official Title: Phase 2 Study of MK-3475 in Patients With Microsatellite Unstable (MSI) Tumors

Clinical Trial IDs

  • ORG STUDY ID: J1365
  • SECONDARY ID: MK-3475-016
  • SECONDARY ID: NA_00085756
  • NCT ID: NCT01876511

Conditions

  • MSI Positive Colorectal Cancer
  • MSI Negative Colorectal Cancer
  • MSI Positive Non-Colorectal Cancers
  • High Tumor Mutation Burden

Interventions

DrugSynonymsArms
MK-3475MSI Positive Colorectal Cancer
MK-3475MSI Negative with Mutator Phenotype

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
MSI Positive Colorectal CancerExperimental
  • MK-3475
MSI Negative Colorectal CancerExperimental
  • MK-3475
MSI Positive Non-Colorectal CancerExperimental
  • MK-3475
MSI Negative with Mutator PhenotypeExperimental
  • MK-3475

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall survival
Time Frame:4 years
Safety Issue:
Description:
Measure:irPFS and PFS in patients with MSI positive and negative tumors at 28 weeks using irRC and RECIST 1.1
Time Frame:4 years
Safety Issue:
Description:
Measure:Best overall response rate and disease control rate in patients with MSI positive and negative tumors
Time Frame:4 years
Safety Issue:
Description:
Measure:Number of participants experiencing immune-related toxicities (IRAEs)
Time Frame:4 years
Safety Issue:
Description:
Measure:Does MSI as a marker predict treatment response
Time Frame:4 years
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Trial Keywords

  • MSI
  • MSS
  • MLH 1
  • MSH 2
  • MSH 6
  • PMS2
  • BRAF pV600E
  • TGFBR2
  • Mutation load
  • tumor mutation load
  • mutation burden
  • tumor mutation burden
  • hypermutation
  • POLE
  • MSI Negative with Mutator Phenotype (High Tumor Mutation Burden)

Last Updated