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Study of Favezelimab (MK-4280) as Monotherapy and in Combination With Pembrolizumab (MK-3475) With or Without Chemotherapy or Lenvatinib (MK-7902) AND Favezelimab/Pembrolizumab (MK-4280A) as Monotherapy in Adults With Advanced Solid Tumors (MK-4280-001)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02720068
Recruitment Status : Active, not recruiting
First Posted : March 25, 2016
Last Update Posted : May 1, 2023
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Study Description
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Brief Summary:
This is a safety and pharmacokinetics study of favezelimab as monotherapy and in combination with pembrolizumab AND favezelimab/pembrolizumab 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 favezelimab as monotherapy or favezelimab in combination with pembrolizumab. Part B is a dose confirmation design to estimate the recommended Phase 2 dose (RP2D), as determined by dose-limiting toxicity, for favezelimab in combination with pembrolizumab or pembrolizumab and lenvatinib in participants with advanced solid tumors. Part B will also assess the efficacy of favezelimab as monotherapy; favezelimab in combination with pembrolizumab with and without chemotherapy; favezelimab in combination with pembrolizumab and lenvatinib; and favezelimab/pembrolizumab as monotherapy in expansion cohorts. Participants who have completed the initial course of treatment and have investigator-determined progressive disease may be eligible for a second course of an additional 17 cycles of study treatment.

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

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 576 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 or Lenvatinib (E7080/MK-7902) in Subjects With Advanced Solid Tumors
Actual Study Start Date : May 2, 2016
Estimated Primary Completion Date : March 1, 2024
Estimated Study Completion Date : March 1, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Part A: Favezelimab Dose A
Participants receive favezelimab Dose A intravenous (IV) infusion on Day 1 of each 21-day cycle.
 Biological: Favezelimab
IV infusion
Other Name: MK-4280
Experimental: Part A: Favezelimab Dose B
Participants receive favezelimab Dose B IV infusion on Day 1 of each 21-day cycle.
 Biological: Favezelimab
IV infusion
Other Name: MK-4280
Experimental: Part A: Favezelimab Dose C
Participants receive favezelimab Dose C IV infusion on Day 1 of each 21-day cycle.
 Biological: Favezelimab
IV infusion
Other Name: MK-4280
Experimental: Part A: Favezelimab Dose D
Participants receive favezelimab Dose D IV infusion on Day 1 of each 21-day cycle.
 Biological: Favezelimab
IV infusion
Other Name: MK-4280
Experimental: Part A: Favezelimab Dose E
Participants receive favezelimab Dose E IV infusion on Day 1 of each 21-day cycle.
 Biological: Favezelimab
IV infusion
Other Name: MK-4280
Experimental: Part A: Favezelimab Dose A+Pembro
Participants receive favezelimab 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: Favezelimab
IV infusion
Other Name: MK-4280

Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Experimental: Part A: Favezelimab Dose B+Pembro
Participants receive favezelimab 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: Favezelimab
IV infusion
Other Name: MK-4280

Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Experimental: Part A: Favezelimab Dose C+Pembro
Participants receive favezelimab 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: Favezelimab
IV infusion
Other Name: MK-4280

Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Experimental: Part A: Favezelimab Dose D+Pembro
Participants receive favezelimab 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: Favezelimab
IV infusion
Other Name: MK-4280

Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Experimental: Part A: Favezelimab Dose E+Pembro
Participants receive favezelimab 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: Favezelimab
IV infusion
Other Name: MK-4280

Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Experimental: Part B: Favezelimab Monotherapy Dose
Participants receive favezelimab monotherapy dose IV infusion on Day 1 of each 21-day cycle.
 Biological: Favezelimab
IV infusion
Other Name: MK-4280
Experimental: Part B: Favezelimab Dose F+Pembro
Participants receive favezelimab 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: Favezelimab
IV infusion
Other Name: MK-4280

Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Experimental: Part B: Favezelimab Dose G+Pembro
Participants receive favezelimab 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: Favezelimab
IV infusion
Other Name: MK-4280

Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Experimental: Part B: Favezelimab Dose H+Pembro
Participants receive favezelimab 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: Favezelimab
IV infusion
Other Name: MK-4280

Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Experimental: Part B: Favezelimab Dose G+Pembro+mFOLFOX7
Participants receive favezelimab 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: Favezelimab
IV infusion
Other Name: MK-4280

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: Favezelimab Dose G+Pembro+FOLFIRI
Participants receive favezelimab 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: Favezelimab
IV infusion
Other Name: MK-4280

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: Favezelimab/Pembrolizumab
Participants receive favezelimab/pembrolizumab (favezelimab and pembrolizumab administered as a co-formulation) IV infusion on Day 1 of each 21-day cycle.
 Biological: Favezelimab/Pembrolizumab
IV infusion
Other Name: MK-4280A
Experimental: Part B: Favezelimab Dose G+Pembro+Lenvatinib
Participants receive favezelimab 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 oral lenvatinib (20 mg) each day of 21-day cycle.
 Biological: Favezelimab
IV infusion
Other Name: MK-4280

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

Drug: Lenvatinib
Oral
Other Names:
  • E7080
  • MK-7902
  • LENVIMA®


Outcome Measures
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Primary Outcome Measures :
  1. Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) [ Time Frame: Up to approximately 52 weeks ]
  2. Number of Participants Who Experience at Least One Adverse Event (AE) [ Time Frame: Up to approximately 7 years ]
  3. Number of Participants Who Discontinue Study Drug Due to an AE [ Time Frame: Up to approximately 7 years ]

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

Eligibility Criteria
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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, is not pregnant or breastfeeding, and if of child-bearing potential, is willing to use an adequate method of contraception for the course of the study and for at least 180 days after the last dose of chemotherapy, 120 days after the last dose of pembrolizumab or favezelimab, or 30 days after the last dose of lenvatinib, whichever occurs last.
  • If male with a female partner(s) of child-bearing potential, both must agree to use an adequate method of contraception starting with the first dose of study drug through 95 days after the last dose of study drug.

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 judgement (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.
  • Has clinically significant heart disease that affects normal activities.
  • 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.
Contacts and Locations
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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


Sponsors and Collaborators
Merck Sharp & Dohme LLC
Investigators
Layout table for investigator information
Study Director: Medical Director Merck Sharp & Dohme LLC
More Information
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Additional Information:

Publications:
Study of Favezelimab (MK-4280) as Monotherapy and in Combination With Pembrolizumab (MK-3475) With or Without Chemotherapy or Lenvatinib (MK-7902) AND Favezelimab/Pembrolizumab (MK-4280A) as Monotherapy in Adults With Advanced Solid Tumors (MK-4280-001) - Full Text View - ClinicalTrials.gov

Layout table for additonal information
Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT02720068    
Other Study ID Numbers: 4280-001
MK-4280-001 ( Other Identifier: Merck Protocol Number )
183971 ( Other Identifier: JAPIC-CTI )
2017-001464-38 ( EudraCT Number )
First Posted: March 25, 2016    Key Record Dates
Last Update Posted: May 1, 2023
Last Verified: April 2023
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

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Sharp & Dohme LLC:
PD1
PD-1
PDL1
PD-L1
Additional relevant MeSH terms:
Layout table for MeSH terms
Leucovorin
Pembrolizumab
Fluorouracil
Oxaliplatin
Irinotecan
Lenvatinib
Calcium
Levoleucovorin
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
 Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antidotes
Protective Agents
Vitamin B Complex
Vitamins
Micronutrients
Protein Kinase Inhibitors