NeoplasmsPhase 1NCT02720068
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)
A Phase 1 study testing Favezelimab, Pembrolizumab and Oxaliplatin in people with Neoplasms, run by Merck Sharp & Dohme LLC.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- Favezelimab, Pembrolizumab and Oxaliplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 481 participants
- Where
- No sites listed yet
- Study dates
- 2 May 2016to 15 Mar 2024
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
About this study
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
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.
Read the detailed description
All participants who completed the first course were eligible for second course treatment after Sponsor consultation if there was investigator-determined progressive disease after initial treatment had been been completed.
- Conditions
- Neoplasms
- Being tested
- Favezelimab, Pembrolizumab, Oxaliplatin, Irinotecan, Leucovorin (Calcium Folinate)
- Keywords
- Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2), Lymphocyte-activation gene 3 (LAG3, LAG-3, CD223)
- Medical subject headings
- Neoplasms, Parkinson Disease 4, Autosomal Dominant Lewy Body
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FavezelimabBiological
Also called MK-4280
IV infusion
PembrolizumabBiological
Also called MK-3475, KEYTRUDA®
IV infusion
OxaliplatinDrug
Also called ELOXATIN®
IV infusion
IrinotecanDrug
Also called CAMPTOSAR®
IV infusion
Leucovorin (Calcium Folinate)Drug
Also called WELLCOVORIN®
IV infusion
Fluorouracil [5-FU]Drug
Also called ADRUCIL®
IV infusion
Favezelimab/PembrolizumabBiological
Also called MK-4280A
IV infusion
LenvatinibDrug
Also called E7080, MK-7902, LENVIMA®
Oral
| Study group | Role | What they receive |
|---|---|---|
| Part A: Favezelimab 7 mg Monotherapy | Experimental | Participants received favezelimab 7 mg intravenous (IV) infusion on Day 1 of each 21-day cycle. Receives: Biological: Favezelimab |
| Part A: Favezelimab 21 mg Monotherapy | Experimental | Participants received favezelimab 21 mg IV infusion on Day 1 of each 21-day cycle. Receives: Biological: Favezelimab |
| Part A: Favezelimab 70 mg Monotherapy | Experimental | Participants received favezelimab 70 mg IV infusion on Day 1 of each 21-day cycle. Receives: Biological: Favezelimab |
| Part A: Favezelimab 210 mg Monotherapy | Experimental | Participants received favezelimab 210 mg IV infusion on Day 1 of each 21-day cycle. Receives: Biological: Favezelimab |
| Part A: Favezelimab 700 mg Monotherapy | Experimental | Participants received favezelimab 700 mg IV infusion on Day 1 of each 21-day cycle. Receives: Biological: Favezelimab |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Experimental | Participants received favezelimab 7 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle. Receives: Biological: Favezelimab; Biological: Pembrolizumab |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Experimental | Participants received favezelimab 21 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle. Receives: Biological: Favezelimab; Biological: Pembrolizumab |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | Experimental | Participants received favezelimab 70 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle. Receives: Biological: Favezelimab; Biological: Pembrolizumab |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | Experimental | Participants received favezelimab 210 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle. Receives: Biological: Favezelimab; Biological: Pembrolizumab |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | Experimental | Participants received favezelimab 700 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle. Receives: Biological: Favezelimab; Biological: Pembrolizumab |
| Part B: Favezelimab 800 mg Monotherapy (Arm 1) | Experimental | Participants received favezelimab 800 mg monotherapy IV infusion on Day 1 of each 21-day cycle. Receives: Biological: Favezelimab |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | Experimental | Participants received favezelimab 200 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle. Receives: Biological: Favezelimab; Biological: Pembrolizumab |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Experimental | Participants received favezelimab 700 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle. Receives: Biological: Favezelimab; Biological: Pembrolizumab |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Experimental | Participants received favezelimab 800 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle. Receives: Biological: Favezelimab; Biological: Pembrolizumab |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Experimental | Participants received favezelimab 800 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg 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]). Receives: Biological: Favezelimab; Biological: Pembrolizumab; Drug: Oxaliplatin; Drug: Leucovorin (Calcium Folinate); Drug: Fluorouracil [5-FU] |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Experimental | Participants received favezelimab 800 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion 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). Receives: Biological: Favezelimab; Biological: Pembrolizumab; Drug: Irinotecan; Drug: Leucovorin (Calcium Folinate); Drug: Fluorouracil [5-FU] |
| Part B: MK-4280A (Arm 5) | Experimental | Participants received MK-4280A, a coformulation of favezelimab 800 mg + pembrolizumab 200 mg IV infusion on Day 1 of each 21-day cycle. Receives: Biological: Favezelimab/Pembrolizumab |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) | Experimental | Participants received favezelimab 800 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle PLUS oral lenvatinib 20 mg once daily. Receives: Biological: Favezelimab; Biological: Pembrolizumab; Drug: Lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)
DLTs were assessed during the first cycle (21 days) \& were defined as: Grade (Gr) 4 nonhematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days, except Gr 4 thrombocytopenia of any duration or Gr 3 thrombocytopenia associated with bleeding; Gr 3 nonhematologic toxicity lasting ≥3 days despite optimal supportive care (with exceptions); Gr 3 or 4 nonhematologic lab abnormality (if medical intervention was required, lead to hospitalization, or persisted for >1 week); Gr 3 or 4 febrile neutropenia; any drug-related AE that caused the participant to discontinue treatment during Cycle 1; Grade 5 toxicity; Any treatment-related toxicity that causes ≥2-week delay in initiation of Cycle 2.
Measured: Up to 21 days (Cycle 1)
Number of Participants Who Experienced an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE is presented.
Measured: Up to approximately 31.3 months
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study treatment due to an AE is presented.
Measured: Up to approximately 28.3 months
Secondary outcomes (11)
Objective Response Rate (ORR) for Part B Participants
ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experienced a CR or PR is presented.
Measured: Up to approximately 92 months
Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab
Blood for serum samples was collected at pre-specified time points to determine the AUC0-inf of favezelimab. In addition to time points listed in Time Frame, participants enrolled in mainland China also had samples drawn predose on Day 1 of Cycle 5 and postdose on Day 2 of Cycles 4 and 8. Per protocol, different arms had different sampling schedules and therefore were not analyzed for all cycles.
Measured: Predose, 2 hours post start of infusion, and post infusion on Day 1 of cycles 1-4 and 8; Day 2 postdose in cycle 1; Days 8 and 15 in cycles 2, 4, and 8; and at the discontinuation and safety follow-up visit if performed prior to the end of Cycle 8
Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab
Blood for serum samples was collected at pre-specified time points to determine the AUC0-21 Days of favezelimab. In addition to time points listed in Time Frame, participants enrolled in mainland China also had samples drawn predose on Day 1 of Cycle 5 and postdose on Day 2 of Cycles 4 and 8. Per protocol, different arms had different sampling schedules and therefore were not analyzed for all cycles.
Measured: Predose, 2 hours post start of infusion, and post infusion on Day 1 of cycles 1-4 and 8; Day 2 postdose in cycle 1; Days 8 and 15 in cycles 2, 4, and 8; and at the discontinuation and safety follow-up visit if performed prior to the end of Cycle 8
Maximum Serum Concentration (Cmax) of Favezelimab
Blood for serum samples was collected at pre-specified time points to determine the Cmax of favezelimab. In addition to time points listed in Time Frame, participants enrolled in mainland China also had samples drawn predose on Day 1 of Cycle 5 and postdose on Day 2 of Cycles 4 and 8. Per protocol, different arms had different sampling schedules and therefore were not analyzed for all cycles.
Measured: Predose, 2 hours post start of infusion, and post infusion on Day 1 of cycles 1-4 and 8; Day 2 postdose in cycle 1; Days 8 and 15 in cycles 2, 4, and 8; and at the discontinuation and safety follow-up visit if performed prior to the end of Cycle 8
AUC0-inf of Pembrolizumab
Blood for serum samples was collected at pre-specified time points to determine the AUC0-inf of pembrolizumab. In addition to time points listed in Time Frame, participants enrolled in mainland China also had samples drawn predose on Day 1 of Cycle 5 and postdose on Day 2 of Cycles 4 and 8. Per protocol, different arms had different sampling schedules and therefore were not analyzed for all cycles.
Measured: Predose, 2 hours post start of infusion, and post infusion on Day 1 of cycles 1-4 and 8; Day 2 postdose in cycle 1; Days 8 and 15 in cycles 2, 4, and 8; and at the discontinuation and safety follow-up visit if performed prior to the end of Cycle 8
AUC0-21 Days of Pembrolizumab
Blood for serum samples was collected at pre-specified time points to determine the AUC0-21 Days of pembrolizumab. In addition to time points listed in Time Frame, participants enrolled in mainland China also had samples drawn predose on Day 1 of Cycle 5 and postdose on Day 2 of Cycles 4 and 8. Per protocol, different arms had different sampling schedules and therefore were not analyzed for all cycles.
Measured: Predose, 2 hours post start of infusion, and post infusion on Day 1 of cycles 1-4 and 8; Day 2 postdose in cycle 1; Days 8 and 15 in cycles 2, 4, and 8; and at the discontinuation and safety follow-up visit if performed prior to the end of Cycle 8
Cmax of Pembrolizumab
Blood for serum samples was collected at pre-specified time points to determine the Cmax of pembrolizumab. In addition to time points listed in Time Frame, participants enrolled in mainland China also had samples drawn predose on Day 1 of Cycle 5 and postdose on Day 2 of Cycles 4 and 8. Per protocol, different arms had different sampling schedules and therefore were not analyzed for all cycles.
Measured: Predose, 2 hours post start of infusion, and post infusion on Day 1 of cycles 1-4 and 8; Day 2 postdose in cycle 1; Days 8 and 15 in cycles 2, 4, and 8; and at the discontinuation and safety follow-up visit if performed prior to the end of Cycle 8
Predose Serum Concentration of Favezelimab
Blood for serum samples was collected at pre-specified time points to determine the predose serum concentration of favezelimab, which is presented.
Measured: Predose on Day 1 of cycles 1-4, 6, and 8. Per protocol, different arms had different sampling schedules and therefore were not analyzed for all cycles.
AUC0-inf of Lenvatinib
Blood for serum samples was collected at pre-specified time points to determine the AUC0-inf of lenvatinib.
Measured: Up to 4 hours postdose, and between 6-10 hours postdose on Cycle 1 Day 1; Predose and between 2-12 hours postdose on Cycle 1 Day 15; Predose, between 0.5-4 hours postdose, and between 6-10 hours postdose on Cycle 2 Day 1
AUC0-21 Days of Lenvatinib
Blood for serum samples was collected at pre-specified time points to determine the AUC0-21 Days of lenvatinib.
Measured: Up to 4 hours postdose, and between 6-10 hours postdose on Cycle 1 Day 1; Predose and between 2-12 hours postdose on Cycle 1 Day 15; Predose, between 0.5-4 hours postdose, and between 6-10 hours postdose on Cycle 2 Day 1
Cmax of Lenvatinib
Blood for serum samples was collected at pre-specified time points to determine the Cmax of lenvatinib.
Measured: Up to 4 hours postdose, and between 6-10 hours postdose on Cycle 1 Day 1; Predose and between 2-12 hours postdose on Cycle 1 Day 15; Predose, between 0.5-4 hours postdose, and between 6-10 hours postdose on Cycle 2 Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2016 (estimated)
- Study start2 May 2016
- Primary completion15 Mar 2024
- Study completion15 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Participants were allocated to arms in a non-random fashion, except in the case of those with gastric cancer enrolled in Part B, who were randomized 1:1 between Arm 2A and Arm 2B (favezelimab 200 mg and 800 mg, respectively). Part B initiated after determination of a favezelimab recommended phase 2 dose (RP2D) from Part A.
- Masking
- None (open label)
- Enrolment
- 481 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02720068
- Sponsor's protocol ID
- 4280-001
- Other IDs
- MK-4280-001, 183971, 2017-001464-38, 2017
- Status last verified
- May 2025
- First submitted
- 22 Mar 2016
- Last updated
- 30 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
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
Garralda E, Sukari A, Lakhani NJ, Patnaik A, Lou Y, Im SA, Golan T, Geva R, Wermke M, de Miguel M, Palcza J, Jha S, Chaney M, Abraham AK, Healy J, Falchook GS. A first-in-human study of the anti-LAG-3 antibody favezelimab plus pembrolizumab in previously treated, advanced microsatellite stable colorectal cancer. ESMO Open. 2022 Dec;7(6):100639. doi: 10.1016/j.esmoop.2022.100639. Epub 2022 Dec 6.
PubMed 36493599
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02720068
- Acronym / sponsor ID
- 4280-001
- Conditions
- Neoplasms
- Keywords
- Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2), Lymphocyte-activation gene 3 (LAG3, LAG-3, CD223)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 481 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 2 May 2016 (actual)
- Primary completion
- 15 Mar 2024 (actual)
- Study completion
- 15 Mar 2024 (actual)
- First posted
- 25 Mar 2016 (estimated)
- Results
- Posted 30 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
All participants who completed the first course were eligible for second course treatment after Sponsor consultation if there was investigator-determined progressive disease after initial treatment had been been completed.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 18
- Model description
- Participants were allocated to arms in a non-random fashion, except in the case of those with gastric cancer enrolled in Part B, who were randomized 1:1 between Arm 2A and Arm 2B (favezelimab 200 mg and 800 mg, respectively). Part B initiated after determination of a favezelimab recommended phase 2 dose (RP2D) from Part A.
| Arm | Type | Receives |
|---|---|---|
| Part A: Favezelimab 7 mg Monotherapy | Experimental | Biological: FavezelimabParticipants received favezelimab 7 mg intravenous (IV) infusion on Day 1 of each 21-day cycle. |
| Part A: Favezelimab 21 mg Monotherapy | Experimental | Biological: FavezelimabParticipants received favezelimab 21 mg IV infusion on Day 1 of each 21-day cycle. |
| Part A: Favezelimab 70 mg Monotherapy | Experimental | Biological: FavezelimabParticipants received favezelimab 70 mg IV infusion on Day 1 of each 21-day cycle. |
| Part A: Favezelimab 210 mg Monotherapy | Experimental | Biological: FavezelimabParticipants received favezelimab 210 mg IV infusion on Day 1 of each 21-day cycle. |
| Part A: Favezelimab 700 mg Monotherapy | Experimental | Biological: FavezelimabParticipants received favezelimab 700 mg IV infusion on Day 1 of each 21-day cycle. |
| Part A: Favezelimab 7 mg + Pembrolizumab 200 mg | Experimental | Biological: Favezelimab, Biological: PembrolizumabParticipants received favezelimab 7 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle. |
| Part A: Favezelimab 21 mg + Pembrolizumab 200 mg | Experimental | Biological: Favezelimab, Biological: PembrolizumabParticipants received favezelimab 21 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle. |
| Part A: Favezelimab 70 mg + Pembrolizumab 200 mg | Experimental | Biological: Favezelimab, Biological: PembrolizumabParticipants received favezelimab 70 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle. |
| Part A: Favezelimab 210 mg + Pembrolizumab 200 mg | Experimental | Biological: Favezelimab, Biological: PembrolizumabParticipants received favezelimab 210 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle. |
| Part A: Favezelimab 700 mg + Pembrolizumab 200 mg | Experimental | Biological: Favezelimab, Biological: PembrolizumabParticipants received favezelimab 700 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle. |
| Part B: Favezelimab 800 mg Monotherapy (Arm 1) | Experimental | Biological: FavezelimabParticipants received favezelimab 800 mg monotherapy IV infusion on Day 1 of each 21-day cycle. |
| Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A) | Experimental | Biological: Favezelimab, Biological: PembrolizumabParticipants received favezelimab 200 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle. |
| Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B) | Experimental | Biological: Favezelimab, Biological: PembrolizumabParticipants received favezelimab 700 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle. |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C) | Experimental | Biological: Favezelimab, Biological: PembrolizumabParticipants received favezelimab 800 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle. |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) | Experimental | Biological: Favezelimab, Biological: Pembrolizumab, Drug: Oxaliplatin, Drug: Leucovorin (Calcium Folinate), Drug: Fluorouracil [5-FU]Participants received favezelimab 800 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg 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]). |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) | Experimental | Biological: Favezelimab, Biological: Pembrolizumab, Drug: Irinotecan, Drug: Leucovorin (Calcium Folinate), Drug: Fluorouracil [5-FU]Participants received favezelimab 800 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion 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). |
| Part B: MK-4280A (Arm 5) | Experimental | Biological: Favezelimab/PembrolizumabParticipants received MK-4280A, a coformulation of favezelimab 800 mg + pembrolizumab 200 mg IV infusion on Day 1 of each 21-day cycle. |
| Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) | Experimental | Biological: Favezelimab, Biological: Pembrolizumab, Drug: LenvatinibParticipants received favezelimab 800 mg IV infusion on Day 1 of each 21-day cycle PLUS pembrolizumab 200 mg IV infusion administered sequentially on Day 1 of each 21-day cycle PLUS oral lenvatinib 20 mg once daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FavezelimabAlso: MK-4280IV infusion | Biological | Part A: Favezelimab 21 mg + Pembrolizumab 200 mg, Part A: Favezelimab 21 mg Monotherapy, Part A: Favezelimab 210 mg + Pembrolizumab 200 mg, Part A: Favezelimab 210 mg Monotherapy, Part A: Favezelimab 7 mg + Pembrolizumab 200 mg, Part A: Favezelimab 7 mg Monotherapy, Part A: Favezelimab 70 mg + Pembrolizumab 200 mg, Part A: Favezelimab 70 mg Monotherapy, Part A: Favezelimab 700 mg + Pembrolizumab 200 mg, Part A: Favezelimab 700 mg Monotherapy, Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A), Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B), Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C), Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4), Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6), Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3), Part B: Favezelimab 800 mg Monotherapy (Arm 1) |
| PembrolizumabAlso: MK-3475, KEYTRUDA®IV infusion | Biological | Part A: Favezelimab 21 mg + Pembrolizumab 200 mg, Part A: Favezelimab 210 mg + Pembrolizumab 200 mg, Part A: Favezelimab 7 mg + Pembrolizumab 200 mg, Part A: Favezelimab 70 mg + Pembrolizumab 200 mg, Part A: Favezelimab 700 mg + Pembrolizumab 200 mg, Part B: Favezelimab 200 mg + Pembrolizumab 200 mg (Arm 2A), Part B: Favezelimab 700 mg + Pembrolizumab 200 mg (Arm 2B), Part B: Favezelimab 800 mg + Pembrolizumab 200 mg (Arm 2C), Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4), Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6), Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) |
| OxaliplatinAlso: ELOXATIN®IV infusion | Drug | Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) |
| IrinotecanAlso: CAMPTOSAR®IV infusion | Drug | Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4) |
| Leucovorin (Calcium Folinate)Also: WELLCOVORIN®IV infusion | Drug | Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4), Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) |
| Fluorouracil [5-FU]Also: ADRUCIL®IV infusion | Drug | Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + FOLFIRI (Arm 4), Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + mFOLFOX7 (Arm 3) |
| Favezelimab/PembrolizumabAlso: MK-4280AIV infusion | Biological | Part B: MK-4280A (Arm 5) |
| LenvatinibAlso: E7080, MK-7902, LENVIMA®Oral | Drug | Part B: Favezelimab 800 mg + Pembrolizumab 200 mg + Lenvatinib 20 mg (Arm 6) |
Primary outcome
Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)
Time frame: Up to 21 days (Cycle 1)
DLTs were assessed during the first cycle (21 days) \& were defined as: Grade (Gr) 4 nonhematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days, except Gr 4 thrombocytopenia of any duration or Gr 3 thrombocytopenia associated with bleeding; Gr 3 nonhematologic toxicity lasting ≥3 days despite optimal supportive care (with exceptions); Gr 3 or 4 nonhematologic lab abnormality (if medical intervention was required, lead to hospitalization, or persisted for >1 week); Gr 3 or 4 febrile neutropenia; any drug-related AE that caused the participant to discontinue treatment during Cycle 1; Grade 5 toxicity; Any treatment-related toxicity that causes ≥2-week delay in initiation of Cycle 2.
Number of Participants Who Experienced an Adverse Event (AE)
Time frame: Up to approximately 31.3 months
An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE is presented.
Number of Participants Who Discontinued Study Treatment Due to an AE
Time frame: Up to approximately 28.3 months
An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study treatment due to an AE is presented.
11 secondary outcomes
Objective Response Rate (ORR) for Part B Participants
Time frame: Up to approximately 92 months
Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Favezelimab
Time frame: Predose, 2 hours post start of infusion, and post infusion on Day 1 of cycles 1-4 and 8; Day 2 postdose in cycle 1; Days 8 and 15 in cycles 2, 4, and 8; and at the discontinuation and safety follow-up visit if performed prior to the end of Cycle 8
Area Under the Curve From Time 0 to 21 Days (AUC0-21 Days) of Favezelimab
Time frame: Predose, 2 hours post start of infusion, and post infusion on Day 1 of cycles 1-4 and 8; Day 2 postdose in cycle 1; Days 8 and 15 in cycles 2, 4, and 8; and at the discontinuation and safety follow-up visit if performed prior to the end of Cycle 8
Maximum Serum Concentration (Cmax) of Favezelimab
Time frame: Predose, 2 hours post start of infusion, and post infusion on Day 1 of cycles 1-4 and 8; Day 2 postdose in cycle 1; Days 8 and 15 in cycles 2, 4, and 8; and at the discontinuation and safety follow-up visit if performed prior to the end of Cycle 8
AUC0-inf of Pembrolizumab
Time frame: Predose, 2 hours post start of infusion, and post infusion on Day 1 of cycles 1-4 and 8; Day 2 postdose in cycle 1; Days 8 and 15 in cycles 2, 4, and 8; and at the discontinuation and safety follow-up visit if performed prior to the end of Cycle 8
AUC0-21 Days of Pembrolizumab
Time frame: Predose, 2 hours post start of infusion, and post infusion on Day 1 of cycles 1-4 and 8; Day 2 postdose in cycle 1; Days 8 and 15 in cycles 2, 4, and 8; and at the discontinuation and safety follow-up visit if performed prior to the end of Cycle 8
Cmax of Pembrolizumab
Time frame: Predose, 2 hours post start of infusion, and post infusion on Day 1 of cycles 1-4 and 8; Day 2 postdose in cycle 1; Days 8 and 15 in cycles 2, 4, and 8; and at the discontinuation and safety follow-up visit if performed prior to the end of Cycle 8
Predose Serum Concentration of Favezelimab
Time frame: Predose on Day 1 of cycles 1-4, 6, and 8. Per protocol, different arms had different sampling schedules and therefore were not analyzed for all cycles.
AUC0-inf of Lenvatinib
Time frame: Up to 4 hours postdose, and between 6-10 hours postdose on Cycle 1 Day 1; Predose and between 2-12 hours postdose on Cycle 1 Day 15; Predose, between 0.5-4 hours postdose, and between 6-10 hours postdose on Cycle 2 Day 1
AUC0-21 Days of Lenvatinib
Time frame: Up to 4 hours postdose, and between 6-10 hours postdose on Cycle 1 Day 1; Predose and between 2-12 hours postdose on Cycle 1 Day 15; Predose, between 0.5-4 hours postdose, and between 6-10 hours postdose on Cycle 2 Day 1
Cmax of Lenvatinib
Time frame: Up to 4 hours postdose, and between 6-10 hours postdose on Cycle 1 Day 1; Predose and between 2-12 hours postdose on Cycle 1 Day 15; Predose, between 0.5-4 hours postdose, and between 6-10 hours postdose on Cycle 2 Day 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundStudy 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
- Results publication: PubMed 36493599Garralda E, Sukari A, Lakhani NJ, Patnaik A, Lou Y, Im SA, Golan T, Geva R, Wermke M, de Miguel M, Palcza J, Jha S, Chaney M, Abraham AK, Healy J, Falchook GS. A first-in-human study of the anti-LAG-3 antibody favezelimab plus pembrolizumab in previously treated, advanced microsatellite stable colorectal cancer. ESMO Open. 2022 Dec;7(6):100639. doi: 10.1016/j.esmoop.2022.100639. Epub 2022 Dec 6.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Favezelimab, Pembrolizumab and Oxaliplatin in people with Neoplasms, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 May 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) (time frame: Up to 21 days (Cycle 1)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02720068, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2025.