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)

Lymphoma, Non-Hodgkin Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03598608
• Other study ID #: 4280-003
• Secondary ID: MK-4280-0032023-
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 17, 2018
• Est. completion date: April 19, 2028

Study information

• Verified date: June 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 174
• Est. completion date: April 19, 2028
• Est. primary completion date: April 19, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Hodgkin Disease
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin

Intervention

Biological:
• pembrolizumab
Administered as an IV infusion every 3 weeks (Q3W)
• Favezelimab
Administered as an IV infusion Q3W

Locations

Country	Name	City	State
Australia	Monash Health ( Site 0201)	Clayton	Victoria
Australia	Concord Repatriation & General Hospital ( Site 0203)	Concord	New South Wales
Australia	St Vincent s Hospital (Melbourne) Limited ( Site 0202)	Fitzroy	Victoria
Australia	Princess Alexandra Hospital ( Site 0204)	Woollongabba	Queensland
Canada	Jewish General Hospital ( Site 0105)	Montreal	Quebec
Canada	Princess Margaret Cancer Centre ( Site 0100)	Toronto	Ontario
Canada	BC Cancer ( Site 0107)	Vancouver	British Columbia
Canada	CancerCare Manitoba ( Site 0101)	Winnipeg	Manitoba
Germany	U. klinikum Koeln AOER ( Site 0326)	Koeln	Nordrhein-Westfalen
Germany	Universitaetsklinikum Leipzig AOeR ( Site 0327)	Leipzig	Sachsen
Israel	Rambam Medical Center ( Site 0382)	Haifa
Israel	Hadassah Ein Karem Jerusalem ( Site 0383)	Jerusalem
Israel	Chaim Sheba Medical Center. ( Site 0380)	Ramat Gan
Israel	Sourasky Medical Center ( Site 0381)	Tel Aviv
Italy	A.O. Universitaria Policlinico S. Orsola-Malpighi ( Site 0351)	Bologna	Emilia-Romagna
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori ( Site 0354)	Meldola	Forli-Cesena
Italy	Humanitas-U.O di Oncologia medica ed Ematologia ( Site 0352)	Rozzano	Milano
United States	Texas Oncology-Austin Midtown ( Site 8002)	Austin	Texas
United States	Dana Farber Cancer Institute ( Site 0002)	Boston	Massachusetts
United States	City of Hope ( Site 0001)	Duarte	California
United States	Banner MD Anderson Cancer Center ( Site 0020)	Gilbert	Arizona
United States	Ronald Reagan UCLA Medical Center (Radiological Sciences) ( Site 0007)	Los Angeles	California
United States	Pacific Cancer Care ( Site 0006)	Monterey	California
United States	Fox Chase Cancer Center ( Site 0019)	Philadelphia	Pennsylvania
United States	University of California San Francisco ( Site 0023)	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Germany,  Israel,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Experiencing a Dose-limiting Toxicity (DLT)	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.	Cycle 1 (up to 21 days)
Primary	Percentage of Participants Experiencing an Adverse Event (AE)	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	From time of signing informed consent form (ICF) until the end of follow-up (up to approximately 27 months)
Primary	Percentage of Participants with Treatment Discontinuations Due to an AE	Percentage of participants discontinuing study treatment due to an AE	From time of signing informed consent form (ICF) until the end of study treatment (up to approximately 24 months)
Secondary	Objective Response Rate (ORR)	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.	Up to approximately 24 months
Secondary	Serum Concentration of Favezelimab	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.	At designated time points (Up to approximately 25 months)
Secondary	Serum Concentration of Pembrolizumab	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.	At designated time points (Up to approximately 25 months)

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary