Clinical Trials /

Study of MK-1697 in Participants With Advanced Solid Tumors (MK-1697-001)

NCT03515824

Description:

The purpose of this study is to evaluate the safety and preliminary efficacy of MK-1697. There are 2 parts in this study: dose escalation to determine the recommended phase 2 dose (RP2D) and confirm the RP2D (Part A) and cohort expansion to determine preliminary efficacy in participants with colorectal cancer (CRC) or head and neck squamous cell cancer (HNSCC) (Part B).

Related Conditions:
  • Colorectal Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of MK-1697 in Participants With Advanced Solid Tumors (MK-1697-001)
  • Official Title: A Phase 1 Study of MK-1697 in Participants With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 1697-001
  • SECONDARY ID: MK1697-001
  • NCT ID: NCT03515824

Conditions

  • Neoplasms
  • Colorectal Neoplasms
  • Head and Neck Neoplasms

Interventions

DrugSynonymsArms
MK-1697MK-1696 Dose Level A

Purpose

The purpose of this study is to evaluate the safety and preliminary efficacy of MK-1697. There are 2 parts in this study: dose escalation to determine the recommended phase 2 dose (RP2D) and confirm the RP2D (Part A) and cohort expansion to determine preliminary efficacy in participants with colorectal cancer (CRC) or head and neck squamous cell cancer (HNSCC) (Part B).

Trial Arms

NameTypeDescriptionInterventions
MK-1696 Dose Level AExperimentalParticipants receive MK-1697 Dose Level A by intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 administrations (up to approximately 2 years).
  • MK-1697
MK-1697 Dose Level BExperimentalParticipants receive MK-1697 Dose Level B by IV infusion on Day 1 of each 21-day cycle for up to 35 administrations (up to approximately 2 years).
  • MK-1697
MK-1697 Dose Level CExperimentalParticipants receive MK-1697 Dose Level C by IV infusion on Day 1 of each 21-day cycle for up to 35 administrations (up to approximately 2 years).
  • MK-1697
Expansion CohortExperimentalParticipants with select tumor types receive MK-1697 at the RP2D by IV infusion on Day 1 of each 21-day cycle for up to 35 administrations (up to approximately 2 years).
  • MK-1697

Eligibility Criteria

        Inclusion Criteria:

          -  For Part A; has a histologically- or cytologically-confirmed advanced/metastatic solid
             tumor and has received, been intolerant to, or been ineligible for all treatments
             known to confer clinical benefit

          -  For Part B: has 1 of the following histologically or cytologically confirmed tumor
             types that are programmed cell death protein 1 (PD-1) treatment naive:

               -  CRC originating in either the colon or rectum that is locally advanced
                  unresectable or metastatic (ie, Stage IV) and that has received, and progressed
                  on, all available standard-of-care therapies including fluoropyrimidine,
                  oxaliplatin, and irinotecan

               -  HNSCC that is considered incurable by local therapies. The eligible primary tumor
                  locations are oropharynx, oral cavity, hypopharynx, and larynx. Participants may
                  not have a primary tumor site of nasopharynx (any histology). Also, participants
                  must have progressed after receiving platinum-containing systemic therapy

          -  Has measurable disease by RECIST 1.1.

          -  Has an evaluable baseline tumor sample (either a recent or archival) for analysis

          -  Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Has central venous access (eg, portacath, Hickman line, or peripherally inserted
             central catheter [PICC] line) currently inserted or be considered medically fit for
             and willing to undergo the insertion of such a device

          -  Is not pregnant or breastfeeding

          -  Female participants of childbearing potential must agree to use contraception during
             the treatment period and for at least 120 days after the last dose of study treatment

          -  Male participants must agree to use contraception during the treatment period and for
             at least 120 days after the last dose of study treatment and refrain from donating
             sperm during this period

        Exclusion Criteria:

          -  Has a history of a second malignancy, unless potentially curative treatment has been
             completed with no evidence of malignancy for 3 years with the exception of
             participants who underwent successful definitive resection of basal cell carcinoma of
             the skin, superficial bladder cancer or in situ cervical cancer, or other in-situ
             cancers

          -  Has clinically active central nervous system (CNS) metastases and/or carcinomatous
             meningitis

          -  Has had a severe hypersensitivity reaction to treatment with any monoclonal antibody
             and/or components of the study treatment

          -  Has an active infection requiring therapy

          -  Has a history of interstitial lung disease

          -  Has a history of (noninfectious) pneumonitis that required steroids or current
             pneumonitis

          -  Has an active autoimmune disease that has required systemic treatment in the past 2
             years

          -  Has known human immunodeficiency virus (HIV) and/or Hepatitis B or C infections, or
             known to be positive for Hepatitis B antigen/Hepatitis B virus deoxyribonucleic acid
             (DNA) or Hepatitis C Antibody or ribonucleic acid (RNA)

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the study, interfere with participation, make
             administration of the study treatments hazardous, or make it difficult to monitor
             adverse effects in the opinion of the treating investigator

          -  Has a history or current evidence of severe cardiovascular disease, ie, arrhythmias
             requiring chronic treatment, congestive heart failure (New York Heart Association
             [NYHA] Class III or IV) or symptomatic ischemic heart disease.

          -  Has a known psychiatric or substance abuse disorder that would interfere with the
             participant's ability to cooperate with the requirements of the trial

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the study, starting with the screening visit through 120 days
             after the last dose of study treatment

          -  Has not fully recovered from any effects of major surgery without significant
             detectable infection. Surgeries that required general anesthesia must be completed at
             least 2 weeks before first study treatment administration. Surgery requiring
             regional/epidural anesthesia must be completed at least 72 hours before first study
             treatment administration and participants should be recovered

          -  Has known microsatellite instability (MSI) high or (DNA) mismatch repair genes (MMR)
             deficient colorectal cancer. If a participant's MSI status is unknown, a paired blood
             sample for MSI in addition to biomarker testing is required to determine MSI status
             retrospectively (for the CRC expansion cohort only)

          -  Has a positive pregnancy test within 72 hours before the first dose of study treatment

          -  Has had chemotherapy, definitive radiation, or biological cancer therapy within 4
             weeks (2 weeks for palliative radiation) prior to the first dose of study therapy, or
             has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or
             better from any adverse events that were due to cancer therapeutics administered more
             than 4 weeks earlier

          -  Has received prior therapy with an anti-Lymphocyte-activation gene 3 (LAG-3) agent

          -  Has received a live vaccine within 30 days prior to the first dose of study drug

          -  Has undergone a prior stem cell or bone marrow transplant within the last 5 years

          -  Is expected to require any other form of antineoplastic therapy while on study

          -  Is currently participating in or has participated in a study of an investigational
             agent or has used an investigational device within 4 weeks prior to the first dose of
             study treatment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants Who Experience a Dose Limiting Toxicity (DLT) During Cycle 1
Time Frame:Up to 21 days
Safety Issue:
Description:The following toxicities will be considered a DLT, if assessed as related to study treatment: Grade (Gr) 4 non-hematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days; Gr 4 thrombocytopenia; Gr 3 thrombocytopenia associated with bleeding; ≥Gr 3 non-hematologic toxicity with the exception of fatigue lasting ≤3 days, Gr 3 nausea, vomiting, or diarrhea lasting >72 hours despite use of anti-emetics, anti-diarrheals, or other supportive care; Gr 3 rash without use of corticosteroids or anti-inflammatory agents per standard of care; Gr 3 or 4 non-hematologic laboratory value if: medical intervention is required, the abnormality leads to hospitalization, persists for >1 week, or the abnormality results in drug-induced liver injury; Gr or 4 febrile neutropenia; treatment-related toxicity that causes discontinuation; inability to administer ≥75% of the planned dose due to drug-related tolerability; Gr 5 toxicity; delay in Cycle 2 start by >2 weeks due to toxicity.

Secondary Outcome Measures

Measure:Objective Response Rate (ORR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)
Time Frame:Up to approximately 24 months
Safety Issue:
Description:An objective response is defined as a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions). ORR will be assessed by the investigator based on RECIST 1.1 following administration of MK-1697. The percentage of participants who experience a CR or PR will be presented.
Measure:Objective Response Rate (ORR) Per Modified Response Evaluation Criteria In Solid Tumors Version 1.1 for Immune-based Therapeutics (iRECIST)
Time Frame:Up to approximately 24 months
Safety Issue:
Description:An objective response is defined as an immune-based Complete Response (iCR: Disappearance of all target lesions) or immune-based Partial Response (iPR: At least a 30% decrease in the sum of diameters of target lesions). ORR will be assessed by the investigator based on iRECIST following administration of MK-1697. The percentage of participants who experience an iCR or iPR will be presented.
Measure:Area Under the Serum Concentration-Time Curve (AUC) of MK-1697
Time Frame:At designated time points in each 21-day treatment cycle for up to 35 treatment cycles (Up to 24 months)
Safety Issue:
Description:Serum samples are to be collected at specified time points (Cycle 1: Days 1, 2, 3, 8, 15 - predose and 2 hours postdose; Cycles 2 and 3: Days 1, 3, 8, 15 - predose and 2 hours postdose; Cycles 4 through 11: Day 1 - predose and 2 hours postdose; Cycles 12, 16, 20, 24, 28, 32, and 35: Day 1 - predose) for the determination of MK-1697 AUC. The MK-1697 serum AUC will be presented.
Measure:Minimum Serum Concentration (Cmin) of MK-1697
Time Frame:At designated time points in each 21-day treatment cycle for up to 35 treatment cycles (Up to 24 months)
Safety Issue:
Description:Serum samples are to be collected at specified time points (Cycle 1: Days 1, 2, 3, 8, 15 - predose and 2 hours postdose; Cycles 2 and 3: Days 1, 3, 8, 15 - predose and 2 hours postdose; Cycles 4 through 11: Day 1 - predose and 2 hours postdose; Cycles 12, 16, 20, 24, 28, 32, and 35: Day 1 - predose) for the determination of MK-1697 Cmin. The MK-1697 serum Cmin will be presented.
Measure:Maximum Serum Concentration (Cmax) of MK-1697
Time Frame:At designated time points in each 21-day treatment cycle for up to 35 treatment cycles (Up to 24 months)
Safety Issue:
Description:Serum samples are to be collected at specified time points (Cycle 1: Days 1, 2, 3, 8, 15 - predose and 2 hours postdose; Cycles 2 and 3: Days 1, 3, 8, 15 - predose and 2 hours postdose; Cycles 4 through 11: Day 1 - predose and 2 hours postdose; Cycles 12, 16, 20, 24, 28, 32, and 35: Day 1 - predose) for the determination of MK-1697 Cmax. The MK-1697 serum Cmax will be presented.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

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