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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03598608
Ethics application status
Date submitted
16/07/2018
Date registered
26/07/2018
Date last updated
29/05/2020

Titles & IDs
Public title
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)
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
Other interventions - pembrolizumab
Other interventions - MK-4280

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.


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

Other interventions: MK-4280
Administered as an IV infusion Q3W

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Experiencing a Dose-limiting Toxicity (DLT) - 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
Timepoint [1] 0 0
Cycle 1 (up to 21 days)
Primary outcome [2] 0 0
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
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 - Percentage of participants discontinuing study treatment 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) - 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.
Timepoint [1] 0 0
Up to approximately 24 months
Secondary outcome [2] 0 0
Serum Concentration of MK-4280 - 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.
Timepoint [2] 0 0
At designated time points (Up to approximately 25 months)
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
At designated time points (Up to approximately 25 months)

Eligibility
Key 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)
Minimum age
18 Years
Maximum age
No limit
Gender
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

- 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

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/Phase 2
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
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
Heifa
Country [13] 0 0
Israel
State/province [13] 0 0
Tell Abib
Country [14] 0 0
Israel
State/province [14] 0 0
Yerushalayim
Country [15] 0 0
Italy
State/province [15] 0 0
Forli-Cesena
Country [16] 0 0
Italy
State/province [16] 0 0
Milano
Country [17] 0 0
Italy
State/province [17] 0 0
Bologna

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme Corp.
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme Corp.
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
Trialsites@merck.com
Contact person for scientific queries

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