Clinical trial NCT03598608: 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)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Hodgkin Disease
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Keywords: programmed cell death 1 (PD-1, PD1)
programmed cell death ligand 1 (PD-L1, PDL1)
programmed cell death ligand 2 (PD-L2, PDL2)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2018-07-26
Enrollment: 174
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Per protocol amendment 7, the secondary serum concentration endpoints were removed and will not be reported.

Eligibility 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

Primary outcomes:
measure: Percentage of Participants Experiencing a Dose-limiting Toxicity (DLT)
timeFrame: Cycle 1 (up to 21 days)
measure: Percentage of Participants Experiencing an Adverse Event (AE)
timeFrame: From time of signing informed consent form (ICF) until the end of follow-up (up to approximately 27 months)
measure: Percentage of Participants with Treatment Discontinuations Due to an AE
timeFrame: From time of signing informed consent form (ICF) until the end of study treatment (up to approximately 24 months)
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center ( Site 0020)
state: Arizona
city: Duarte
country: United States
facility: City of Hope ( Site 0001)
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center (Radiological Sciences) ( Site 0007)
state: California
city: Monterey
country: United States
facility: Pacific Cancer Care ( Site 0006)
state: California
city: San Francisco
country: United States
facility: University of California San Francisco ( Site 0023)
state: California
city: Boston
country: United States
facility: Dana Farber Cancer Institute ( Site 0002)
state: Massachusetts
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center ( Site 0019)
state: Pennsylvania
city: Austin
country: United States
facility: Texas Oncology-Austin Midtown ( Site 8002)
state: Texas
city: Concord
country: Australia
facility: Concord Repatriation & General Hospital ( Site 0203)
state: New South Wales
city: Woollongabba
country: Australia
facility: Princess Alexandra Hospital ( Site 0204)
state: Queensland
city: Clayton
country: Australia
facility: Monash Health ( Site 0201)
state: Victoria
city: Fitzroy
country: Australia
facility: St Vincent s Hospital (Melbourne) Limited ( Site 0202)
state: Victoria
city: Vancouver
country: Canada
facility: BC Cancer ( Site 0107)
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba ( Site 0101)
state: Manitoba
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre ( Site 0100)
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital ( Site 0105)
state: Quebec
city: Koeln
country: Germany
facility: U. klinikum Koeln AOER ( Site 0326)
state: Nordrhein-Westfalen
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig AOeR ( Site 0327)
state: Sachsen
city: Haifa
country: Israel
facility: Rambam Medical Center ( Site 0382)
city: Jerusalem
country: Israel
facility: Hadassah Ein Karem Jerusalem ( Site 0383)
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center. ( Site 0380)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 0381)
city: Bologna
country: Italy
facility: A.O. Universitaria Policlinico S. Orsola-Malpighi ( Site 0351)
state: Emilia-Romagna
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori ( Site 0354)
state: Forli-Cesena
city: Rozzano
country: Italy
facility: Humanitas-U.O di Oncologia medica ed Ematologia ( Site 0352)
state: Milano
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: