Study of MK-4280 as Monotherapy and in Combination With Pembrolizumab (MK-3475) With or Without Chemotherapy or Lenvatinib AND MK-4280A as Monotherapy in Adults With Advanced Solid Tumors (MK-4280-001)
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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT02720068 |
Recruitment Status :
Recruiting
First Posted : March 25, 2016
Last Update Posted : February 15, 2021
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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 Drug: Lenvatinib | Phase 1 |
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 : | December 13, 2023 |
Estimated Study Completion Date : | December 13, 2023 |

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:
|
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:
|
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:
|
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:
|
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:
|
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:
|
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:
|
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:
|
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:
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:
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 |
Experimental: Part B: MK-4280 Dose G+Pembro+Lenvatinib
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 oral lenvatinib (20 mg) each day of 21-day cycle.
|
Biological: MK-4280
IV infusion Biological: Pembrolizumab IV infusion
Other Names:
Drug: Lenvatinib Oral
Other Names:
|
- Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) [ Time Frame: Up to approximately 2 years ]
- Number of Participants Who Experience at Least One Adverse Event (AE) [ Time Frame: Up to approximately 2 years ]
- Number of Participants Who Discontinue Study Drug Due to an AE [ Time Frame: Up to approximately 2 years ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- ORR as Determined by RECIST 1.1 as Assessed by Investigator Review of MK-4280 in Combination With Pembrolizumab and Lenvatinib for Participants With Advanced Solid Tumors in Cohort G [ Time Frame: Up to approximately 2 years ]
- Serum Concentration of MK-4280 When Administered as Monotherapy [ Time Frame: At designated time points (Up to approximately 2 years) ]
- Serum Concentration of MK-4280 When Administered in Combination With Pembrolizumab [ Time Frame: At designated time points (Up to approximately 2 years) ]
- Serum Concentration of MK-4280 When Administered in Combination With Pembrolizumab and mFOLFOX7 [ Time Frame: At designated time points (Up to approximately 2 years) ]
- Serum Concentration of MK-4280 When Administered in Combination With Pembrolizumab and FOLFIRI [ Time Frame: At designated time points (Up to approximately 2 years) ]
- Serum Concentration of Pembrolizumab When Administered in Combination With MK-4280 and mFOLFOX7 [ Time Frame: At designated time points (Up to approximately 2 years) ]
- Serum Concentration of Pembrolizumab When Administered in Combination With MK-4280 and FOLFIRI [ Time Frame: At designated time points (Up to approximately 2 years) ]
- 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) ]
- Serum Concentration of MK-4280 When Administered Sequentially With Pembrolizumab [ Time Frame: At designated time points (Up to approximately 2 years) ]
- 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) ]
- Serum Concentration of Pembrolizumab When Administered Sequentially With MK-4280 [ Time Frame: At designated time points (Up to approximately 2 years) ]
- Serum Concentration of MK-4280 When Administered in Combination With Pembrolizumab and Lenvatinib [ Time Frame: At designated time points (Up to approximately 2 years) ]
- Serum Concentration of Pembrolizumab When Administered in Combination With MK-4280 and Lenvatinib [ Time Frame: At designated time points (Up to approximately 2 years) ]
- Serum Concentration of Lenvatinib When Administered in Combination With Pembrolizumab and MK-4280 [ Time Frame: At designated time points (Up to approximately 2 years) ]

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.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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 through 120 days after the last dose of study drug.
- 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. 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.
- 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.

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
Contact: Toll Free Number | 1-888-577-8839 |
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, 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 | |
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 48 22ý478 43 24 | |
Spain | |
Merck Sharp and Dohme de Espana S.A. | Recruiting |
Madrid, Spain | |
Contact: Lourdes Lopez-Bravo (0034) 913210654 |
Study Director: | Medical Director | Merck Sharp & Dohme Corp. |
Responsible Party: | Merck Sharp & Dohme Corp. |
ClinicalTrials.gov Identifier: | NCT02720068 |
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: | February 15, 2021 |
Last Verified: | February 2021 |
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 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
PD1 PD-1 PDL1 PD-L1 |
Leucovorin Fluorouracil Oxaliplatin Pembrolizumab Irinotecan Lenvatinib Calcium Levoleucovorin Calcium-Regulating Hormones and Agents Physiological Effects of Drugs Antimetabolites Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Antineoplastic Agents |
Immunosuppressive Agents Immunologic Factors Antineoplastic Agents, Immunological Topoisomerase I Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Antidotes Protective Agents Vitamin B Complex Vitamins Micronutrients Nutrients Growth Substances Protein Kinase Inhibitors |