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Phase 2 N=113 Treatment

Study of MK-3475 in Patients With Microsatellite Unstable (MSI) Tumors (Cohorts A, B and C)

MSI Positive Colorectal Cancer · MSI Negative Colorectal Cancer · MSI Positive Non-Colorectal Cancers

Enrolled (actual)
113
Serious AEs
9.7%
Results posted
Jan 2020
Primary outcome: Primary: Immune-related Progression Free Survival (irPFS) at 20 Weeks in MSI Positive and Negative Colorectal Adenocarcinoma Participants Using Immune Related Response Criteria (irRC) During Stages 1 and 2 — 88; 12 percentage of participants

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
MK-3475 (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Primary completion
Aug 2019

Outcome Measures

OutcomeResultp-value
PRIMARY
Immune-related Progression Free Survival (irPFS) at 20 Weeks in MSI Positive and Negative Colorectal Adenocarcinoma Participants Using Immune Related Response Criteria (irRC) During Stages 1 and 2
88; 12
PRIMARY
Immune-related Objective Response Rate in MSI Positive and Negative Colorectal Adenocarcinoma Participants Using Immune Related Response Criteria (irRC) During Stages 1 and 2
67; 0
PRIMARY
Immune-related Progression Free Survival (irPFS) at 20 Weeks in MSI Positive Non-colorectal Adenocarcinoma Participants Using Immune Related Response Criteria (irRC) During Stages 1 and 2
67
PRIMARY
Objective Response Rate in MSI Positive Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
54; 55
PRIMARY
Progression Free Survival (PFS) at 20 Weeks in MSI Positive Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
75; 68
SECONDARY
Overall Survival (OS)
NA; 36.71; 148.86
SECONDARY
Immune-related Progression Free Survival (irPFS) at 28 Weeks in MSI Positive and Negative Solid Tumor Malignancies Using Immune Related Response Criteria (irRC)
70; 12; 64
SECONDARY
Objective Response Rate (ORR) in MSI Positive and Negative Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
54; 0; 55
SECONDARY
Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity
12; 0; 13
SECONDARY
Progression Free Survival (PFS) at 28 Weeks in MSI Positive and Negative Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
70; 16; 64
SECONDARY
Disease Control Rate in MSI Positive and Negative Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
80; 16; 70
SECONDARY
Does MSI as a Marker Predict Treatment Response
54; 0; 55

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 three different patient populations. These include: 1. patients with MSI positive colon cancer, 2. patients with MSI negative colon cancer and 3. patients with other MSI positive cancers.

Eligibility Criteria

Inclusion Criteria

  • Cohort A only: Patients with microsatellite instability (MSI) positive colorectal cancer
  • Cohort B only: Patients with MSI negative colorectal cancer
  • Cohort C only: Patients with MSI positive non-colorectal 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 participants' 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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01876511). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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