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JOURNAL ONKOLOGIE – STUDIE

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)

Rekrutierend

NCT-Nummer:
NCT03598608

Studienbeginn:
Oktober 2018

Letztes Update:
25.04.2024

Wirkstoff:
Pembrolizumab, Favezelimab

Indikation (Clinical Trials):
Lymphoma, Hematologic Neoplasms, Hodgkin Disease, Lymphoma, Non-Hodgkin, Lymphoma, B-Cell

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Merck Sharp & Dohme LLC

Collaborator:
-

Studienleiter

Medical Director
Study Director
Merck Sharp & Dohme LLC

Kontakt

Studienlocations
(3 von 25)

Pacific Cancer Care ( Site 0006)
93940 Monterey
United StatesAktiv, nicht rekrutierend» Google-Maps
Dana Farber Cancer Institute ( Site 0002)
02215 Boston
United StatesAktiv, nicht rekrutierend» Google-Maps
Fox Chase Cancer Center ( Site 0019)
19111 Philadelphia
United StatesAbgeschlossen» Google-Maps
Texas Oncology-Austin Midtown ( Site 8002)
78705 Austin
United StatesAbgeschlossen» Google-Maps
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

1. 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.

2. 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

3. 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:

1. 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.

2. 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.

3. 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.

Studien-Arme

  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).

Geprüfte Regime

  • pembrolizumab (KEYTRUDA® / MK-3475 / ):
    Administered as an IV infusion every 3 weeks (Q3W)
  • Favezelimab (MK-4280):
    Administered as an IV infusion Q3W

Quelle: ClinicalTrials.gov


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