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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03598608




Registration number
NCT03598608
Ethics application status
Date submitted
16/07/2018
Date registered
26/07/2018
Date last updated
20/11/2024

Titles & IDs
Public title
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)
Scientific 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
Secondary ID [1] 0 0
MK-4280-003
Secondary ID [2] 0 0
4280-003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hodgkin Disease 0 0
Lymphoma, Non-Hodgkin 0 0
Lymphoma, B-Cell 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Hodgkin's

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - pembrolizumab
Treatment: Other - Favezelimab

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).


Treatment: Other: pembrolizumab
Administered as an IV infusion every 3 weeks (Q3W)

Treatment: Other: Favezelimab
Administered as an IV infusion Q3W
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Experiencing a Dose-limiting Toxicity (DLT)
Timepoint [1] 0 0
Cycle 1 (up to 21 days)
Primary outcome [2] 0 0
Percentage of Participants Experiencing an Adverse Event (AE)
Timepoint [2] 0 0
From time of signing informed consent form (ICF) until the end of follow-up (up to approximately 27 months)
Primary outcome [3] 0 0
Percentage of Participants with Treatment Discontinuations Due to an AE
Timepoint [3] 0 0
From time of signing informed consent form (ICF) until the end of study treatment (up to approximately 24 months)
Secondary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
Up to approximately 24 months
Secondary outcome [2] 0 0
Serum Concentration of Favezelimab
Timepoint [2] 0 0
At designated time points (Up to approximately 25 months)
Secondary outcome [3] 0 0
Serum Concentration of Pembrolizumab
Timepoint [3] 0 0
At designated time points (Up to approximately 25 months)

Eligibility
Key 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)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/10/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
19/10/2028
Actual
Sample size
Target
174
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Concord Repatriation & General Hospital ( Site 0203) - Concord
Recruitment hospital [2] 0 0
Princess Alexandra Hospital ( Site 0204) - Woollongabba
Recruitment hospital [3] 0 0
Monash Health ( Site 0201) - Clayton
Recruitment hospital [4] 0 0
St Vincent s Hospital (Melbourne) Limited ( Site 0202) - Fitzroy
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
4102 - Woollongabba
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
Canada
State/province [6] 0 0
British Columbia
Country [7] 0 0
Canada
State/province [7] 0 0
Manitoba
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
Canada
State/province [9] 0 0
Quebec
Country [10] 0 0
Germany
State/province [10] 0 0
Nordrhein-Westfalen
Country [11] 0 0
Germany
State/province [11] 0 0
Sachsen
Country [12] 0 0
Israel
State/province [12] 0 0
Haifa
Country [13] 0 0
Israel
State/province [13] 0 0
Jerusalem
Country [14] 0 0
Israel
State/province [14] 0 0
Ramat Gan
Country [15] 0 0
Israel
State/province [15] 0 0
Tel Aviv
Country [16] 0 0
Italy
State/province [16] 0 0
Emilia-Romagna
Country [17] 0 0
Italy
State/province [17] 0 0
Forli-Cesena
Country [18] 0 0
Italy
State/province [18] 0 0
Milano

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT03598608
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03598608