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Study of MK-4280 as Monotherapy and in Combination With Pembrolizumab (MK-3475) With or Without Chemotherapy AND MK-4280A as Monotherapy in Adults With Advanced Solid Tumors (MK-4280-001)

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ClinicalTrials.gov Identifier: NCT02720068
Recruitment Status : Recruiting
First Posted : March 25, 2016
Last Update Posted : June 20, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
This is a safety and pharmacokinetics study of MK-4280 as monotherapy and in combination with pembrolizumab (MK-3475) AND MK-4280A as monotherapy in adults with metastatic solid tumors for which there is no available therapy which may convey clinical benefit. Part A of this study is a dose escalation design in which participants receive MK-4280 as monotherapy or MK-4280 in combination with pembrolizumab. Part B is a dose confirmation design to estimate the recommended Phase 2 dose (RPTD), as determined by dose-limiting toxicity, for MK-4280 in combination with pembrolizumab in participants with advanced solid tumors. Part B will also assess the efficacy of MK-4280 as monotherapy and in combination with pembrolizumab with and without chemotherapy AND MK-4280A as monotherapy in expansion cohorts.

Condition or disease Intervention/treatment Phase
Neoplasms Biological: MK-4280 Biological: Pembrolizumab Drug: Oxaliplatin Drug: Irinotecan Drug: Leucovorin (Calcium Folinate) Drug: Fluorouracil [5-FU] Biological: MK-4280A Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 488 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Trial of MK-4280 as Monotherapy and in Combination With Pembrolizumab With or Without Chemotherapy in Subjects With Advanced Solid Tumors
Actual Study Start Date : May 2, 2016
Estimated Primary Completion Date : May 13, 2022
Estimated Study Completion Date : May 13, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part A: MK-4280 Dose A
Participants receive MK-4280 Dose A intravenous (IV) infusion on Day 1 of each 21-day cycle.
Biological: MK-4280
IV infusion

Experimental: Part A: MK-4280 Dose B
Participants receive MK-4280 Dose B IV infusion on Day 1 of each 21-day cycle.
Biological: MK-4280
IV infusion

Experimental: Part A: MK-4280 Dose C
Participants receive MK-4280 Dose C IV infusion on Day 1 of each 21-day cycle.
Biological: MK-4280
IV infusion

Experimental: Part A: MK-4280 Dose D
Participants receive MK-4280 Dose D IV infusion on Day 1 of each 21-day cycle.
Biological: MK-4280
IV infusion

Experimental: Part A: MK-4280 Dose E
Participants receive MK-4280 Dose E IV infusion on Day 1 of each 21-day cycle.
Biological: MK-4280
IV infusion

Experimental: Part A: MK-4280 Dose A+Pembro
Participants receive MK-4280 Dose A IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab IV infusion administered sequentially on Day 1 of each 21-day cycle.
Biological: MK-4280
IV infusion

Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®

Experimental: Part A: MK-4280 Dose B+Pembro
Participants receive MK-4280 Dose B IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab IV infusion administered sequentially on Day 1 of each 21-day cycle.
Biological: MK-4280
IV infusion

Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®

Experimental: Part A: MK-4280 Dose C+Pembro
Participants receive MK-4280 Dose C IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab IV infusion administered sequentially on Day 1 of each 21-day cycle.
Biological: MK-4280
IV infusion

Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®

Experimental: Part A: MK-4280 Dose D+Pembro
Participants receive MK-4280 Dose D IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab IV infusion administered sequentially on Day 1 of each 21-day cycle.
Biological: MK-4280
IV infusion

Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®

Experimental: Part A: MK-4280 Dose E+Pembro
Participants receive MK-4280 Dose E IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab IV infusion administered sequentially on Day 1 of each 21-day cycle.
Biological: MK-4280
IV infusion

Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®

Experimental: Part B: MK-4280 Monotherapy Dose
Participants receive MK-4280 monotherapy dose IV infusion on Day 1 of each 21-day cycle.
Biological: MK-4280
IV infusion

Experimental: Part B: MK-4280 Dose F+Pembro
Participants receive MK-4280 Dose F IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab IV infusion administered sequentially on Day 1 of each 21-day cycle.
Biological: MK-4280
IV infusion

Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®

Experimental: Part B: MK-4280 Dose G+Pembro
Participants receive MK-4280 Dose G IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab IV infusion administered sequentially on Day 1 of each 21-day cycle.
Biological: MK-4280
IV infusion

Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®

Experimental: Part B: MK-4280 Dose H+Pembro
Participants receive MK-4280 Dose H IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab IV infusion administered sequentially on Day 1 of each 21-day cycle.
Biological: MK-4280
IV infusion

Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®

Experimental: Part B: MK-4280 Dose G+Pembro+mFOLFOX7
Participants receive MK-4280 Dose G IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab IV infusion administered sequentially on Day 1 of each 21-day cycle PLUS mFOLFOX7 (oxaliplatin 85 mg/m^2 IV, leucovorin [calcium folinate] 400 mg/m^2 IV and fluorouracil [5-FU] 2400 mg/m^2 IV over 46 to 48 hours every 2 weeks [Q2W]).
Biological: MK-4280
IV infusion

Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®

Drug: Oxaliplatin
IV infusion
Other Name: ELOXATIN®

Drug: Leucovorin (Calcium Folinate)
IV infusion
Other Name: WELLCOVORIN®

Drug: Fluorouracil [5-FU]
IV infusion
Other Name: ADRUCIL®

Experimental: Part B: MK-4280 Dose G+Pembro+FOLFIRI
Participants receive MK-4280 Dose G IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab IV administered sequentially on Day 1 of each 21-day cycle PLUS FOLFIRI (irinotecan 180 mg/m^2 IV, leucovorin [calcium folinate] 400 mg/m^2 IV and 5-FU 2400 mg/m^2 IV over 46 to 48 hours Q2W).
Biological: MK-4280
IV infusion

Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®

Drug: Irinotecan
IV infusion
Other Name: CAMPTOSAR®

Drug: Leucovorin (Calcium Folinate)
IV infusion
Other Name: WELLCOVORIN®

Drug: Fluorouracil [5-FU]
IV infusion
Other Name: ADRUCIL®

Experimental: Part B: MK-4280A
Participants receive MK-4280A (MK-4280 and pembrolizumab administered as a co-formulation) IV infusion on Day 1 of each 21-day cycle.
Biological: MK-4280A
IV infusion




Primary Outcome Measures :
  1. Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) [ Time Frame: Up to approximately 2 years ]
  2. Number of Participants Who Experience at Least One Adverse Event (AE) [ Time Frame: Up to approximately 2 years ]
  3. Number of Participants Who Discontinue Study Drug Due to an AE [ Time Frame: Up to approximately 2 years ]

Secondary Outcome Measures :
  1. Objective Response Rate (ORR) as Determined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as Assessed by Investigator Review of MK-4280 in Combination With Pembrolizumab [ Time Frame: Up to approximately 2 years ]
  2. ORR as Determined by RECIST 1.1 as Assessed by Investigator Review of Two Doses of MK-4280 in Combination With Pembrolizumab for Participants with Advanced Solid Tumors in Cohort E [ Time Frame: Up to approximately 2 years ]
  3. ORR as Determined by RECIST 1.1 as Assessed by Investigator Review of MK-4280 in Combination With Pembrolizumab and mFOLFOX7 for Participants with Advanced Solid Tumors in Cohort B [ Time Frame: Up to approximately 2 years ]
  4. ORR as Determined by RECIST 1.1 as Assessed by Investigator Review of MK-4280 in Combination With Pembrolizumab and FOLFIRI for Participants with Advanced Solid Tumors in Cohort B [ Time Frame: Up to approximately 2 years ]
  5. Serum Concentration of MK-4280 When Administered as Monotherapy [ Time Frame: At designated time points (Up to approximately 2 years) ]
  6. Serum Concentration of MK-4280 When Administered in Combination With Pembrolizumab [ Time Frame: At designated time points (Up to approximately 2 years) ]
  7. Serum Concentration of MK-4280 When Administered in Combination With Pembrolizumab and mFOLFOX7 [ Time Frame: At designated time points (Up to approximately 2 years) ]
  8. Serum Concentration of MK-4280 When Administered in Combination With Pembrolizumab and FOLFIRI [ Time Frame: At designated time points (Up to approximately 2 years) ]
  9. At designated time points (Up to approximately 2 years) [ Time Frame: At designated time points (Up to approximately 2 years) ]
  10. Serum Concentration of Pembrolizumab When Administered in Combination With MK-4280 and mFOLFOX7 [ Time Frame: At designated time points (Up to approximately 2 years) ]
  11. Serum Concentration of Pembrolizumab When Administered in Combination With MK-4280 and FOLFIRI [ Time Frame: At designated time points (Up to approximately 2 years) ]
  12. Serum Concentration of MK-4280 When Administered as a Co-Formulation With Pembrolizumab (MK-4280A) [ Time Frame: At designated time points (Up to approximately 2 years) ]
  13. Serum Concentration of MK-4280 When Administered Sequentially With Pembrolizumab [ Time Frame: At designated time points (Up to approximately 2 years) ]
  14. Serum Concentration of Pembrolizumab When Administered as a Co-Formulation With MK-4280 (MK-4280A) [ Time Frame: At designated time points (Up to approximately 2 years) ]
  15. Serum Concentration of Pembrolizumab When Administered Sequentially With MK-4280 [ Time Frame: At designated time points (Up to approximately 2 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.


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

Inclusion Criteria:

  • Part A and Part B: Has histologically or cytologically-confirmed metastatic solid tumor.
  • Has measurable disease by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) 1.1 criteria.
  • Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  • Demonstrates adequate organ function
  • If female of child-bearing potential, is willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug.
  • If male with a female partner(s) of child-bearing potential, must agree to use an adequate method of contraception starting with the first dose of study drug through 120 days after the last dose of study drug. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.

Exclusion Criteria:

  • Has had chemotherapy, radiation or biological cancer therapy within 4 weeks prior to the first dose of study drug, or has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 0 or 1 from the AEs due to cancer therapeutics administered more than 4 weeks earlier (this includes participants with previous immunomodulatory therapy with residual immune-related [ir]AEs).
  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study drug.
  • Has received previous treatment with another agent targeting the lymphocyte-activation gene 3 (LAG-3) receptor.
  • Has received previous treatment with an immunomodulatory therapy (e.g. anti-programmed cell death-1/anti-programmed cell death-ligand 1 [anti-PD-1/anti-PD-L1] or cytotoxic T-lymphocyte-associated protein 4 [CTLA 4] agent) and was discontinued from that therapy due to a Grade 3 or higher irAE.
  • Is expected to require any other form of antineoplastic therapy while on study.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy in excess of replacement doses, or on any other form of immunosuppressive medication.
  • Has a history of a previous, additional malignancy, unless potentially curative treatment has been completed, with no evidence of malignancy for 5 years. Time frame exceptions include successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer or in situ cervical cancer, or other in situ cancers.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Has had a severe hypersensitivity reaction to treatment with another monoclonal antibody.
  • Has an active autoimmune disease or a documented history of autoimmune disease, except vitiligo or resolved childhood asthma/atopy.
  • Has an active infection requiring therapy.
  • Has history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has had a prior stem cell or bone marrow transplant.
  • Has a known history of or screens positive for Human Immunodeficiency Virus (HIV), active chronic or acute Hepatitis B or Hepatitis C.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
  • Is a regular user as determined by investigator judgment (including "recreational use") of any illicit drugs or has a recent history (within the last year) of substance abuse (including alcohol), at the time of signing informed consent.
  • Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
  • 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 drug.
  • Has clinically significant heart disease that affects normal activities.
  • Has had major surgery in the past 4 weeks.
  • Has received a live-virus vaccine within 30 days of planned start of study drug. Seasonal flu vaccines that do not contain live virus are permitted.

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): NCT02720068


Contacts
Layout table for location contacts
Contact: Toll Free Number 1-888-577-8839

Locations
Layout table for location information
United States, Arizona
Call for Information (Investigational Site 0021) Recruiting
Phoenix, Arizona, United States, 85054
United States, California
Call for Information (Investigational Site 0008) Recruiting
Encinitas, California, United States, 92024
Call for Information (Investigational Site 0009) Recruiting
Fresno, California, United States, 93720
United States, Colorado
Call for Information (Investigational Site 0019) Recruiting
Denver, Colorado, United States, 80218
United States, Florida
Call for Information (Investigational Site 0022) Recruiting
Jacksonville, Florida, United States, 32224
United States, Michigan
Call for Information (Investigational Site 0012) Recruiting
Detroit, Michigan, United States, 48201
Call for Information (Investigational Site 0003) Recruiting
Grand Rapids, Michigan, United States, 49503
United States, Minnesota
Call for Information (Investigational Site 0020) Recruiting
Rochester, Minnesota, United States, 55905
United States, Tennessee
Call for Information (Investigational Site 0002) Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Call for Information (Investigational Site 0017) Recruiting
Houston, Texas, United States, 77030
Call for Information (Investigational Site 0001) Recruiting
San Antonio, Texas, United States, 78229
Canada, Quebec
Merck Canada Recruiting
Kirkland, Quebec, Canada, H9H 4M7
Contact: Medical Information Centre Centre d'information medicale Merck Canada Inc.    514-428-8600 / 1-800-567-2594      
Germany
MSD Sharp & Dohme GmbH Recruiting
Haar, Germany
Contact: German Medical Information Center    49 800 673 673 673      
Israel
Merck Sharp & Dohme Co. Ltd. Recruiting
Hod Hasharon, Israel
Contact: Gally Teper    972-9-9533310      
Japan
MSD K.K. Recruiting
Chiyoda-Ku, Tokyo, Japan, 102-8667
Contact: Japan Call Center    81-3-6272-1957      
Korea, Republic of
MSD Korea LTD Recruiting
Seoul, Korea, Republic of, 4130
Contact: Jongho Ahn    82-2-331-2000 2015      
Poland
MSD Polska Sp. Z o.o. Recruiting
Warsaw, Poland
Contact: Thomas Johansson    48224784324      
Spain
Merck Sharp and Dohme de Espana S.A. Recruiting
Madrid, Spain
Contact: Lourdes Lopez-Bravo    (0034) 913210654      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Study Director: Medical Director Merck Sharp & Dohme Corp.

Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02720068     History of Changes
Other Study ID Numbers: 4280-001
2017-001464-38 ( EudraCT Number )
MK-4280-001 ( Other Identifier: Merck Protocol Number )
183971 ( Other Identifier: JAPIC-CTI )
First Posted: March 25, 2016    Key Record Dates
Last Update Posted: June 20, 2019
Last Verified: June 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: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck Sharp & Dohme Corp.:
PD1
PD-1
PDL1
PD-L1

Additional relevant MeSH terms:
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Calcium
Calcium, Dietary
Oxaliplatin
Pembrolizumab
Irinotecan
Fluorouracil
Levoleucovorin
Leucovorin
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Bone Density Conservation Agents
Antineoplastic Agents
Antineoplastic Agents, Immunological
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Antidotes
Protective Agents
Vitamin B Complex
Vitamins
Micronutrients
Nutrients
Growth Substances