Study to Evaluate the Safety and Efficacy of a Combination of Favezelimab (MK-4280) and Pembrolizumab (MK-3475) in Participants With Hematologic Malignancies (MK-4280-003)
|
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: NCT03598608 |
|
Recruitment Status :
Recruiting
First Posted : July 26, 2018
Last Update Posted : October 14, 2022
|
Sponsor:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Brief Summary:
This study will evaluate the safety and efficacy of favezelimab (MK-4280) in combination with pembrolizumab (MK-3475) using a non-randomized study design in participants with the following hematological malignancies:
- classical Hodgkin lymphoma (cHL)
- diffuse large B-cell lymphoma (DLBCL)
- indolent non-Hodgkin lymphoma (iNHL)
This study will also evaluate the safety and efficacy of pembrolizumab or favezelimab administered as monotherapy in participants with cHL using a 1:1 randomized study design.
The study will have 2 phases: a safety lead-in and an efficacy expansion phase. The recommended Phase 2 dose (RP2D) will be determined in the safety lead-in phase by evaluating dose-limiting toxicities.
There is no primary hypothesis for this study.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hodgkin Disease Lymphoma, Non-Hodgkin Lymphoma, B-Cell | Biological: pembrolizumab Biological: Favezelimab | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 174 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Masking Description: | Participants in Part B: Randomized cHL-Monotherapy arm in the study will be randomized (1:1 ratio) to receive pembrolizumab or favezelimab. |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1/Phase 2 Clinical Study to Evaluate the Safety and Efficacy of a Combination of MK-4280 and Pembrolizumab (MK-3475) in Participants With Hematologic Malignancies |
| Actual Study Start Date : | October 17, 2018 |
| Estimated Primary Completion Date : | October 19, 2027 |
| Estimated Study Completion Date : | October 19, 2027 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Pembrolizumab
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Part A: Favezelimab Dose A+pembrolizumab
Participants receive 200 mg pembrolizumab by intravenous (IV) infusion followed by favezelimab Dose A by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).
|
Biological: pembrolizumab
Administered as an IV infusion every 3 weeks (Q3W)
Other Names:
Biological: Favezelimab Administered as an IV infusion Q3W
Other Name: MK-4280 |
|
Experimental: Part A: Favezelimab Dose B+pembrolizumab
Participants receive 200 mg pembrolizumab by IV infusion followed by favezelimab Dose B by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).
|
Biological: pembrolizumab
Administered as an IV infusion every 3 weeks (Q3W)
Other Names:
Biological: Favezelimab Administered as an IV infusion Q3W
Other Name: MK-4280 |
|
Experimental: Part A: Favezelimab Dose C+Pembrolizumab
Participants receive 200 mg pembrolizumab by IV infusion followed by favezelimab Dose C by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).
|
Biological: pembrolizumab
Administered as an IV infusion every 3 weeks (Q3W)
Other Names:
Biological: Favezelimab Administered as an IV infusion Q3W
Other Name: MK-4280 |
|
Experimental: Part B: cHL-Combination Therapy
Participants with cHL receive 200 mg pembrolizumab by IV infusion followed by the recommended Phase 2 dose (RP2D) of favezelimab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).
|
Biological: pembrolizumab
Administered as an IV infusion every 3 weeks (Q3W)
Other Names:
Biological: Favezelimab Administered as an IV infusion Q3W
Other Name: MK-4280 |
|
Experimental: Part B: DLBCL-Combination Therapy
Participants with DLBCL receive 200 mg pembrolizumab by IV infusion followed by the RP2D of favezelimab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).
|
Biological: pembrolizumab
Administered as an IV infusion every 3 weeks (Q3W)
Other Names:
Biological: Favezelimab Administered as an IV infusion Q3W
Other Name: MK-4280 |
|
Experimental: Part B: iNHL-Combination Therapy
Participants with iNHL receive 200 mg pembrolizumab by IV infusion followed by the RP2D of favezelimab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).
|
Biological: pembrolizumab
Administered as an IV infusion every 3 weeks (Q3W)
Other Names:
Biological: Favezelimab Administered as an IV infusion Q3W
Other Name: MK-4280 |
|
Experimental: Part B: Randomized cHL-Monotherapy
Participants with cHL receive either pembrolizumab by IV infusion or the RP2D of favezelimab by IV infusion on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to approximately 2 years).
|
Biological: pembrolizumab
Administered as an IV infusion every 3 weeks (Q3W)
Other Names:
Biological: Favezelimab Administered as an IV infusion Q3W
Other Name: MK-4280 |
Primary Outcome Measures :
- Percentage of Participants Experiencing a Dose-limiting Toxicity (DLT) [ Time Frame: Cycle 1 (up to 21 days) ]DLT will be defined as any drug-related adverse event (AE) observed during the DLT evaluation period (Cycle 1) that results in a change to a given dose or a delay in initiating the next cycle and reported as the percentage of participants experiencing a DLT defined by the National Cancer Institute Common Terminology for Adverse Events version 4.0.
- Percentage of Participants Experiencing an Adverse Event (AE) [ Time Frame: From time of signing informed consent form (ICF) until the end of follow-up (up to approximately 27 months) ]Percentage of participants experiencing an AE defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study treatment
- Percentage of Participants with Treatment Discontinuations Due to an AE [ Time Frame: From time of signing informed consent form (ICF) until the end of study treatment (up to approximately 24 months) ]Percentage of participants discontinuing study treatment due to an AE
Secondary Outcome Measures :
- Objective Response Rate (ORR) [ Time Frame: Up to approximately 24 months ]ORR is defined as the percentage of participants in the analysis population who had a Complete Response or a Partial Response per lymphoma disease response criteria (Cheson et. al., 2007) as assessed by the investigator.
- Serum Concentration of Favezelimab [ Time Frame: At designated time points (Up to approximately 25 months) ]Blood samples will be collected at designated time points for the determination of the serum concentration of favezelimab. For Cycles 1 and 8: Day 1 at predose, end of infusion, and 4 hours postdose; Days 8 and 15 at any time. Cycles 2 through 7, Cycles 9 through 16 and every 4 cycles thereafter: Day 1 at predose. Blood samples will also be collected at the 30-day follow-up visit.
- Serum Concentration of Pembrolizumab [ Time Frame: At designated time points (Up to approximately 25 months) ]Blood samples will be collected at designated time points for the determination of the serum concentration of pembrolizumab. For Cycles 1 and 8: Day 1 at predose, end of infusion, and 4 hours postdose; Days 8 and 15 at any time. Cycles 2 through 7, Cycles 9 through 16 and every 4 cycles thereafter: Day 1 at predose. Blood samples will also be collected at the 30-day follow-up visit.
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.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Has measurable disease, defined as ≥1 lesion that can be accurately measured in 2 dimensions with diagnostic quality cross sectional anatomic imaging (computed tomography or magnetic resonance imaging). Minimum measurement must be >15 mm in the longest diameter or >10 mm in the short axis
- Is able to provide a core or excisional tumor biopsy for biomarker analysis from an archival (within 3 months) or newly obtained biopsy at screening
- Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
Exclusion Criteria:
- Has known clinically active central nervous system (CNS) involvement
- Has received prior therapy with an anti-lymphocyte activation gene-3 (LAG-3) antibody
- Has received chimeric antigen receptors (CAR)-T-cell therapy for cHL and DLBCL Cohorts
- Has received prior anticancer therapy or thoracic radiation therapy within 14 days before the first dose of study treatment
- Has ≥Grade 2 non-hematological residual toxicities from prior therapy
- Has had a prior anticancer monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤Grade 1 or at baseline) from AEs due to agents administered ≥4 weeks earlier
- Has received a live vaccine within 30 days prior to first dose of study treatment. Administration of killed vaccines are allowed
- Has received an investigational agent or used an investigational device within 4 weeks prior to intervention administration
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug
- Has a known additional malignancy that is progressing or requires active treatment with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
- Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
- Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
- Has an active infection requiring intravenous systemic therapy
- Has a known history of human immunodeficiency virus (HIV) infection
- Has known, active hepatitis B or hepatitis C infection
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
- Has had an allogeneic hematopoetic stem cell/solid organ transplantation within the last 5 years
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): NCT03598608
Contacts
| Contact: Toll Free Number | 1-888-577-8839 | Trialsites@merck.com |
Locations
Show 25 study locations
Sponsors and Collaborators
Merck Sharp & Dohme LLC
Investigators
| Study Director: | Medical Director | Merck Sharp & Dohme LLC |
Additional Information:
| Responsible Party: | Merck Sharp & Dohme LLC |
| ClinicalTrials.gov Identifier: | NCT03598608 |
| Other Study ID Numbers: |
4280-003 MK-4280-003 ( Other Identifier: Merck ) 2018-001461-16 ( EudraCT Number ) |
| First Posted: | July 26, 2018 Key Record Dates |
| Last Update Posted: | October 14, 2022 |
| Last Verified: | October 2022 |
| 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 |
Keywords provided by Merck Sharp & Dohme LLC:
|
programmed cell death 1 (PD-1, PD1) programmed cell death ligand 1 (PD-L1, PDL1) programmed cell death ligand 2 (PD-L2, PDL2) |
Additional relevant MeSH terms:
|
Lymphoma Hematologic Neoplasms Hodgkin Disease Lymphoma, Non-Hodgkin Lymphoma, B-Cell Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders |
Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Neoplasms by Site Hematologic Diseases Pembrolizumab Antineoplastic Agents, Immunological Antineoplastic Agents |