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JOURNAL ONKOLOGIE – STUDIE

Study to Evaluate the Safety and Efficacy of a Combination of MK-4280 and Pembrolizumab (MK-3475) in Participants With Hematologic Malignancies (MK-4280-003)

Rekrutierend

NCT-Nummer:
NCT03598608

Studienbeginn:
Oktober 2018

Letztes Update:
02.03.2021

Wirkstoff:
Pembrolizumab, MK-4280

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

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Merck Sharp & Dohme Corp.

Collaborator:
-

Studienleiter

Medical Director
Study Director
Merck Sharp & Dohme Corp.

Kontakt

Studienlocations
(3 von 25)

Alle anzeigen

Studien-Informationen

Brief Summary:

This study will evaluate the safety and efficacy of MK-4280 in combination with pembrolizumab

(MK-3475) in participants with hematological malignancies:

- classical Hodgkin lymphoma (cHL)

- diffuse large B-cell lymphoma (DLBCL)

- indolent non-Hodgkin lymphoma (iNHL) The study will have 2 phases: a safety lead-in and

an efficacy expansion phase. The recommended Phase 2 dose (RPTD) will be determined in

the safety lead-in phase by evaluating dose-limiting toxicities.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Has measureable 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

- Has received prior anticancer therapy or thoracic radiation therapy within 14 days

before the first dose of study treatment

- Has ≥Grade 2 non-hematological 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

- 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 28 days before study Day 1

- 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)):
Percentage of participants experiencing a DLT defined by the National Cancer Institute Common Terminology for Adverse Events version 4.0 as: grade (gr) 4 non-hematologic toxicity (not laboratory) gr 4 hematologic toxicity lasting >7 days OR gr 4 platelet count decreased of any duration OR gr 3 platelet count decreased if associated with bleeding any gr 3 non-hematologic toxicity (not laboratory) with the exception of gr 3 nausea, vomiting, or diarrhea (not be considered a DLT unless lasting >3 days despite optimal supportive care) any gr 3 or 4 non-hematologic laboratory abnormality if medical intervention is required, or the abnormality leads to hospitalization, or the abnormality persists for >1 week gr 3 or 4 febrile neutropenia any treatment-related AE which caused participant to discontinue study intervention during the first cycle gr 5 toxicity any treatment-related toxicity which causes a >2-week delay in initiation of Cycle 2

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 (CR: Disappearance of all evidence of disease) or a Partial Response (PR: ≥50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses; no increase should be observed in the size of other nodes, liver, or spleen; and splenic and hepatic nodules must regress by ≥50% in their SPD or, for single nodules, in the greatest transverse diameter) per lymphoma disease response criteria (Cheson et. al., 2007) as assessed by the investigator.

2. Serum Concentration of MK-4280 (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 MK-4280. 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: MK-4280 Dose A+pembrolizumab
    Participants receive 200 mg pembrolizumab by intravenous (IV) infusion followed by MK-4280 Dose A by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles.
  • Experimental: Part A: MK-4280 Dose B+pembrolizumab
    Participants receive 200 mg pembrolizumab by IV infusion followed by MK-4280 Dose B by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles.
  • Experimental: Part A: MK-4280 Dose C+Pembrolizumab
    Participants receive 200 mg pembrolizumab by IV infusion followed by MK-4280 Dose C by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles.
  • Experimental: Part B: cHL
    Participants with cHL receive 200 mg pembrolizumab by IV infusion followed by the RPTD of MK-4280 by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles.
  • Experimental: Part B: DLBCL
    Participants with DLBCL receive 200 mg pembrolizumab by IV infusion followed by the RPTD of MK-4280 by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles.
  • Experimental: Part B: iNHL
    Participants with iNHL receive 200 mg pembrolizumab by IV infusion followed by the RPTD of MK-4280 by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles.

Geprüfte Regime

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

Quelle: ClinicalTrials.gov


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