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Study of MK-3475 (an Antibody That Blocks Negative Signals to T Cells) in Patients With Microsatellite Unstable (MSI) Tumors (Cohort D)

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ClinicalTrials.gov Identifier: NCT04098068
Recruitment Status : Recruiting
First Posted : September 20, 2019
Last Update Posted : September 24, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:
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 patients with MSI (Microsatellite Unstable) negative cancer with a mutator phenotype.

Condition or disease Intervention/treatment Phase
High Tumor Mutation Burden High TMB (Tumor Mutation Burden) MSS (Microsatellite Unstable) Drug: MK-3475 (an Antibody That Blocks Negative Signals to T Cells) Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2 Study of MK-3475 (an Antibody That Blocks Negative Signals to T Cells) in Patients With Microsatellite Unstable (MSI) Tumors
Actual Study Start Date : January 9, 2018
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: MSI (Microsatellite Unstable) Negative with Mutator Phenotype Drug: MK-3475 (an Antibody That Blocks Negative Signals to T Cells)
MK-3475 (an Antibody That Blocks Negative Signals to T Cells) 200 mg/kg flat dose every 21 days




Primary Outcome Measures :
  1. Objective Response Rate (ORR) in Patients with MSI (Microsatellite Unstable)-negative Solid Tumor Malignancies with a Mutator Phenotype [ Time Frame: 4 years ]

Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: 4 years ]
  2. Progression-Free Survival (PFS) in Patients at 28 Weeks Using RECIST 1.1(Response Evaluation Criteria In Solid Tumors) [ Time Frame: 4 years ]
  3. Overall Response Rate (ORR) [ Time Frame: 4 years ]
  4. Disease Control Rate (DCR) [ Time Frame: 4 years ]
  5. Number of Participants Experiencing Immune-related Toxicities (IRAEs) [ Time Frame: 4 years ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with hypermutated MSI (Microsatellite Unstable) negative cancer
  • Have measurable disease
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
  • Adequate organ function as defined by study-specified laboratory tests
  • Must use acceptable form of birth control through the study and for 28 days after final dose of study drug
  • Signed informed consent form
  • Willing and able to comply with study procedures
  • Agree to have a biopsy of their cancer
  • Patients with colon cancer must have received at least two prior cancer therapy regimens.
  • Patients with other cancer types must have received at least one prior cancer therapy
  • Progressive disease

Exclusion Criteria:

  • 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.
  • Patients who have had chemotherapy or biological cancer therapy within 2 weeks prior to the first dose of study drug
  • Patients who have had radiation within 2 weeks prior to the first dose of study drug
  • Patients who have undergone major surgery within 4 weeks of dosing of investigational agent
  • Patients who have received another investigational product or investigational device within 4 weeks prior to receiving study drug
  • Patients who have received any of the following concomitant therapy: Interleukin-2 (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
  • Patients who have received a live vaccine within 4 weeks prior to or after any dose of MK-3475 (exception: inactivated flu vaccines)
  • 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
  • Patient who have had prior treatment with anti-PD-1 (anti-programmed cell death protein 1), anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, or anti-CTLA-4 antibodies
  • 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, central nervous system (CNS) or motor neuropathy considered to be of autoimmune origin.
  • Patients who have known history of infection with HIV, hepatitis B, or hepatitis C
  • Patients with evidence of interstitial lung disease
  • Systemically active steroid use
  • Patients on home oxygen
  • Patients with oxygen saturation of <92% on room air by pulse oximetry
  • Pregnant or lactating
  • Conditions, including alcohol or drug dependence, or intercurrent illness that would affect the patient's ability to comply with study visits and procedures
  • Patient with known active central nervous system metastases and/or carcinomatous meningitis.
  • Patients with primary brain tumors.
  • Requires any other form of systemic or localized antineoplastic therapy while on study
  • Has any tissue or organ allograft
  • Patients with history of allogeneic hematopoeitic stem cell transplant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04098068


Contacts
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Contact: Ellen Lilly-Foreman, RN 443-287-4961 lillyel@jhmi.edu

Locations
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United States, Maryland
Sidney Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21231
Contact: Susan Sartorius-Mergenthaler, RN    410-614-3644    Sartosu@jhmi.edu   
Contact: Ellen Foreman-Lilly, RN    443-287-4961    lillyel@jhmi.edu   
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Marios Giannakis, MD       MGIANNAKIS@PARTNERS.ORG   
Principal Investigator: Marios Giannakis, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Blessing Agunwamba    646-888-4444    agunwamb@mskcc.org   
Principal Investigator: Luis Diaz, MD         
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: John Hays, MD    614-293-6529    John.Hays@osumc.edu   
Principal Investigator: John Hayes, MD         
United States, Oregon
Providence Portland Medical Center Recruiting
Portland, Oregon, United States, 97213
Contact: Todd Crocenzi, MD       Todd.Crocenzi@providence.org   
Principal Investigator: Todd Crocenzi, MD         
United States, Pennsylvania
University of Pennsylvania, Abramson Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Kim R Binder, MD    215-360-0735    Kim.ReissBinder@uphsupenn.edu   
Principal Investigator: Kim R Binder, MD         
University of Pittsburgh Cancer Institute Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: James Lee, MD, PhD       leejj@upmc.edu   
Principal Investigator: James Lee, MD, PhD         
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Dung Le, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT04098068     History of Changes
Other Study ID Numbers: J1365 (Cohort D)
MK-3475-016 ( Other Identifier: Merck )
NA_00085756 ( Other Identifier: JHM IRB )
First Posted: September 20, 2019    Key Record Dates
Last Update Posted: September 24, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
BRAF pv600E (human gene that encodes a protein called B-Raf)
TGFBR2 (transforming growth factor-beta (TGF-β) receptor type 2)
Mutation load
Tumor mutation load
Mutation burden
Tumor mutation burden (TMB)
Hypermutation
POLE
MSI Negative with Mutator Phenotype (High Tumor Mutation Burden)
TMB (Tumor Mutation Burden)
Additional relevant MeSH terms:
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Neoplasms
Pembrolizumab
Antibodies
Immunoglobulins
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Antineoplastic Agents