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)

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03598608
Collaborator
(none)
174
25
7
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Study Details

Study Description

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
  • Biological: pembrolizumab
  • Biological: Favezelimab
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated 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 :
Oct 17, 2018
Anticipated Primary Completion Date :
Oct 19, 2027
Anticipated Study Completion Date :
Oct 19, 2027

Arms and Interventions

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:
  • KEYTRUDA®
  • MK-3475
  • Biological: Favezelimab
    Administered as an IV infusion Q3W
    Other Names:
  • 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:
  • KEYTRUDA®
  • MK-3475
  • Biological: Favezelimab
    Administered as an IV infusion Q3W
    Other Names:
  • 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:
  • KEYTRUDA®
  • MK-3475
  • Biological: Favezelimab
    Administered as an IV infusion Q3W
    Other Names:
  • 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:
  • KEYTRUDA®
  • MK-3475
  • Biological: Favezelimab
    Administered as an IV infusion Q3W
    Other Names:
  • 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:
  • KEYTRUDA®
  • MK-3475
  • Biological: Favezelimab
    Administered as an IV infusion Q3W
    Other Names:
  • 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:
  • KEYTRUDA®
  • MK-3475
  • Biological: Favezelimab
    Administered as an IV infusion Q3W
    Other Names:
  • 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:
  • KEYTRUDA®
  • MK-3475
  • Biological: Favezelimab
    Administered as an IV infusion Q3W
    Other Names:
  • MK-4280
  • Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants Experiencing a Dose-limiting Toxicity (DLT) [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.

    2. Percentage of Participants Experiencing an Adverse Event (AE) [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

    3. Percentage of Participants with Treatment Discontinuations Due to an AE [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

    1. Objective Response Rate (ORR) [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.

    2. Serum Concentration of Favezelimab [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.

    3. Serum Concentration of Pembrolizumab [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Banner MD Anderson Cancer Center ( Site 0020) Gilbert Arizona United States 85234
    2 City of Hope ( Site 0001) Duarte California United States 91010
    3 Ronald Reagan UCLA Medical Center (Radiological Sciences) ( Site 0007) Los Angeles California United States 90095
    4 Pacific Cancer Care ( Site 0006) Monterey California United States 93940
    5 University of California San Francisco ( Site 0023) San Francisco California United States 94143
    6 Dana Farber Cancer Institute ( Site 0002) Boston Massachusetts United States 02215
    7 Fox Chase Cancer Center ( Site 0019) Philadelphia Pennsylvania United States 19111
    8 Texas Oncology-Austin Midtown ( Site 8002) Austin Texas United States 78705
    9 Concord Repatriation & General Hospital ( Site 0203) Concord New South Wales Australia 2139
    10 Princess Alexandra Hospital ( Site 0204) Woollongabba Queensland Australia 4102
    11 Monash Health ( Site 0201) Clayton Victoria Australia 3168
    12 St Vincent s Hospital (Melbourne) Limited ( Site 0202) Fitzroy Victoria Australia 3065
    13 BC Cancer ( Site 0107) Vancouver British Columbia Canada V5Z 1L3
    14 CancerCare Manitoba ( Site 0101) Winnipeg Manitoba Canada R3E 0V9
    15 Princess Margaret Cancer Centre ( Site 0100) Toronto Ontario Canada M5G 2M9
    16 Jewish General Hospital ( Site 0105) Montreal Quebec Canada H3T 1E2
    17 U. klinikum Koeln AOER ( Site 0326) Koeln Nordrhein-Westfalen Germany 50937
    18 Universitaetsklinikum Leipzig AOeR ( Site 0327) Leipzig Sachsen Germany 04103
    19 Rambam Medical Center ( Site 0382) Haifa Israel 3109601
    20 Hadassah Ein Karem Jerusalem ( Site 0383) Jerusalem Israel 9112001
    21 Chaim Sheba Medical Center. ( Site 0380) Ramat Gan Israel 5262001
    22 Sourasky Medical Center ( Site 0381) Tel Aviv Israel 6423906
    23 A.O. Universitaria Policlinico S. Orsola-Malpighi ( Site 0351) Bologna Emilia-Romagna Italy 40138
    24 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori ( Site 0354) Meldola Forli-Cesena Italy 47014
    25 Humanitas-U.O di Oncologia medica ed Ematologia ( Site 0352) Rozzano Milano Italy 20089

    Sponsors and Collaborators

    • Merck Sharp & Dohme LLC

    Investigators

    • Study Director: Medical Director, Merck Sharp & Dohme LLC

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT03598608
    Other Study ID Numbers:
    • 4280-003
    • MK-4280-003
    • 2018-001461-16
    First Posted:
    Jul 26, 2018
    Last Update Posted:
    Aug 22, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 22, 2022