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

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ClinicalTrials.gov Identifier: NCT03515824
Recruitment Status : Recruiting
First Posted : May 4, 2018
Last Update Posted : March 19, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Neoplasms Colorectal Neoplasms Head and Neck Neoplasms Biological: MK-1697 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 122 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of MK-1697 in Participants With Advanced Solid Tumors
Actual Study Start Date : August 13, 2018
Estimated Primary Completion Date : September 11, 2022
Estimated Study Completion Date : September 11, 2022

Arm Intervention/treatment
Experimental: MK-1696 Dose Level A
Participants 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).
Biological: MK-1697
Administered by IV infusion on Day 1 of each 21-day cycle

Experimental: MK-1697 Dose Level B
Participants 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).
Biological: MK-1697
Administered by IV infusion on Day 1 of each 21-day cycle

Experimental: MK-1697 Dose Level C
Participants 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).
Biological: MK-1697
Administered by IV infusion on Day 1 of each 21-day cycle

Experimental: Expansion Cohort
Participants 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).
Biological: MK-1697
Administered by IV infusion on Day 1 of each 21-day cycle




Primary Outcome Measures :
  1. Percentage of Participants Who Experience a Dose Limiting Toxicity (DLT) During Cycle 1 [ Time Frame: Up to 21 days ]
    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.

  2. Percentage of Participants Who Experience At Least One Adverse Event (AE) [ Time Frame: Up to approximately 27 months ]
    An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The percentage of participants who experience at least one AE will be presented.

  3. Percentage of Participants Who Discontinue Study Intervention Due to an Adverse Event (AE) [ Time Frame: Up to approximately 24 months ]
    The percentage of participants who discontinue study intervention due to an AE will be presented.


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Up to approximately 24 months ]
    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.

  2. 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 ]
    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.

  3. 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) ]
    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.

  4. 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) ]
    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.

  5. 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) ]
    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.



Information from the National Library of Medicine

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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:

  • 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

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): NCT03515824


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
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Australia, New South Wales
Scientia Clinical Research ( Site 0100) Recruiting
Randwick, New South Wales, Australia, 2031
Contact: Study Coordinator    +61293825807      
Hong Kong
Queen Mary Hospital ( Site 0200) Recruiting
Hong Kong, Hong Kong
Contact: Study Coordinator    +85222554249      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.

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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03515824     History of Changes
Other Study ID Numbers: 1697-001
MK1697-001 ( Other Identifier: Merck Protocol Number )
First Posted: May 4, 2018    Key Record Dates
Last Update Posted: March 19, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Neoplasms
Colorectal Neoplasms
Head and Neck Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases