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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03918278




Registration number
NCT03918278
Ethics application status
Date submitted
15/04/2019
Date registered
17/04/2019
Date last updated
22/05/2020

Titles & IDs
Public title
A Study of MK-0482 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-0482-001)
Scientific title
A Phase 1b, Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-0482 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced/Metastatic Solid Tumors.
Secondary ID [1] 0 0
MK-0482-001
Secondary ID [2] 0 0
0482-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - MK-0482
Other interventions - pembrolizumab

Experimental: MK-0482 Monotherapy - Participants receive escalating doses of MK-0482 via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 administrations (up to approximately 2 years).

Experimental: MK-0482 + Pembrolizumab Combination Therapy - Participants receive escalating doses of MK-0482 via IV infusion + pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 administrations (up to approximately 2 years).


Other interventions: MK-0482
IV infusion

Other interventions: pembrolizumab
IV infusion

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

Outcomes
Primary outcome [1] 0 0
Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 - DLTs defined as any of the following assessed as treatment (Tx)-related by investigator: Grade (Gr)4 nonhematologic toxicity; Gr4 hematologic toxicity lasting =7 days, except thrombocytopenia; Gr4 thrombocytopenia of any duration; Gr3 thrombocytopenia associated with clinically-significant bleeding; nonhematologic adverse event (AE) =Gr3 in severity, with exceptions; Gr3/4 alanine transaminase (ALT), aspartate transaminase (AST), and/or bilirubin (bili) with exceptions; a protocol-defined elevation of ALT, AST, and bili; Gr3/4 nonhematologic laboratory abnormality if: clinically significant medical intervention is required, leads to hospitalization, persists for >1 week, or results in liver injury with exceptions; Gr3/4 febrile neutropenia; >2 week-delay in starting Cycle 2 due to Tx-related toxicity; Tx-related toxicity resulting in Tx discontinuation during Cycle 1; missing >25% of the MK-0482 and/or pembrolizumab doses during Cycle 1 resulting from Tx-related AE; or Gr5 toxicity.
Timepoint [1] 0 0
Cycle 1 (Up to 21 days)
Primary outcome [2] 0 0
Number of Participants Who Experience at Least One Adverse Event (AE) - An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience at least one AE will be presented.
Timepoint [2] 0 0
Up to approximately 27 months
Primary outcome [3] 0 0
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) - The number of participants who discontinue study treatment due to an AE will be presented.
Timepoint [3] 0 0
Up to approximately 24 months
Secondary outcome [1] 0 0
Minimum Serum Concentration (Cmin) of MK-0482 When Administered as Monotherapy - Blood samples will be obtained at designated time points for the assessment of MK-0482 Cmin (Cycle 1 Day 1: Predose and at end of administration [within 30 minutes after the end of infusion]; Cycle 1 Days 2, 4, 8 and 15: Once daily; Cycles 2, 4, 6, 8 and every 4 cycles thereafter: Predose and at end of administration [within 30 minutes after the end of infusion]; and at end of treatment/discontinuation [Up to approximately 25 months]). Each cycle is 21 days.
Timepoint [1] 0 0
At designated time points (Up to approximately 25 months)
Secondary outcome [2] 0 0
Minimum Serum Concentration (Cmin) of MK-0482 When Administered in Combination with Pembrolizumab - Blood samples will be obtained at designated time points for the assessment of MK-0482 Cmin (Cycle 1 Day 1: Predose and at end of administration [within 30 minutes after the end of infusion]; Cycle 1 Days 2, 4, 8 and 15: Once daily; Cycles 2, 4, 6, 8 and every 4 cycles thereafter: Predose and at end of administration [within 30 minutes after the end of infusion]; and at end of treatment/discontinuation [Up to approximately 25 months]). Each cycle is 21 days.
Timepoint [2] 0 0
At designated time points (Up to approximately 25 months)
Secondary outcome [3] 0 0
Maximum Serum Concentration (Cmax) of MK-0482 When Administered as Monotherapy - Blood samples will be obtained at designated time points for the assessment of MK-0482 Cmax (Cycle 1 Day 1: Predose and at end of administration [within 30 minutes after the end of infusion]; Cycle 1 Days 2, 4, 8 and 15: Once daily; Cycles 2, 4, 6, 8 and every 4 cycles thereafter: Predose and at end of administration [within 30 minutes after the end of infusion]; and at end of treatment/discontinuation [Up to approximately 25 months]). Each cycle is 21 days.
Timepoint [3] 0 0
At designated time points (Up to approximately 25 months)
Secondary outcome [4] 0 0
Maximum Serum Concentration (Cmax) of MK-0482 When Administered in Combination with Pembrolizumab - Blood samples will be obtained at designated time points for the assessment of MK-0482 Cmax (Cycle 1 Day 1: Predose and at end of administration [within 30 minutes after the end of infusion]; Cycle 1 Days 2, 4, 8 and 15: Once daily; Cycles 2, 4, 6, 8 and every 4 cycles thereafter: Predose and at end of administration [within 30 minutes after the end of infusion]; and at end of treatment/discontinuation [Up to approximately 25 months]). Each cycle is 21 days.
Timepoint [4] 0 0
At designated time points (Up to approximately 25 months)
Secondary outcome [5] 0 0
Area Under the Concentration-Time Curve (AUC) of MK-0482 When Administered as Monotherapy - Blood samples will be obtained at designated time points for the assessment of MK-0482 AUC (Cycle 1 Day 1: Predose and at end of administration [within 30 minutes after the end of infusion]; Cycle 1 Days 2, 4, 8 and 15: Once daily; Cycles 2, 4, 6, 8 and every 4 cycles thereafter: Predose and at end of administration [within 30 minutes after the end of infusion]; and at end of treatment/discontinuation [Up to approximately 25 months]). Each cycle is 21 days.
Timepoint [5] 0 0
At designated time points (Up to approximately 25 months)
Secondary outcome [6] 0 0
Area Under the Concentration-Time Curve (AUC) of MK-0482 When Administered in Combination with Pembrolizumab - Blood samples will be obtained at designated time points for the assessment of MK-0482 AUC (Cycle 1 Day 1: Predose and at end of administration [within 30 minutes after the end of infusion]; Cycle 1 Days 2, 4, 8 and 15: Once daily; Cycles 2, 4, 6, 8 and every 4 cycles thereafter: Predose and at end of administration [within 30 minutes after the end of infusion]; and at end of treatment/discontinuation [Up to approximately 25 months]). Each cycle is 21 days.
Timepoint [6] 0 0
At designated time points (Up to approximately 25 months)

Eligibility
Key inclusion criteria
- Has histologically-or cytologically-confirmed advanced/metastatic solid tumors by
pathology report and have received, been intolerant to, or been ineligible for, all
treatments known to confer clinical benefit

- Has measurable disease by Response Evaluation Criteria in Solid Tumors Version 1.1
(RECIST 1.1) as assessed by the local site investigator/radiology

- Has provided an evaluable baseline tumor tissue sample

- Has =1 discrete malignant lesions that are amenable to biopsy

- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

- A female participant is eligible to participate if she is not pregnant or
breastfeeding, and =1 of the following conditions applies: is not a woman of
childbearing potential (WOCBP) OR is using a contraceptive method that is highly
effective or is abstinent from heterosexual intercourse as their preferred and usual
lifestyle during the intervention period and for =120 days after the last dose of
study treatment

- Has a negative highly sensitive pregnancy test within 72 hours before the first dose
of study treatment

- Human immunodeficiency virus (HIV) infected participants must have well controlled HIV
on anti-retroviral therapy (ART)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Has a history of a second malignancy, unless potentially curative treatment has been
completed with no evidence of recurrence for =2 years

- Has a known additional malignancy that is progressing or has required active treatment
within the past 2 years; with the exception of basal cell carcinoma of the skin,
squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma,
cervical cancer in situ) that have undergone potentially curative therapy

- Has known active central nervous system metastases and/or carcinomatous meningitis

- Has had a severe hypersensitivity reaction to treatment with a monoclonal antibody
(mAb) and/or any component of pembrolizumab (MK-3475) or MK-0482

- Has received any prior immunotherapy and was discontinued from that treatment due to a
Grade 3 or higher immune-related adverse event (irAE)

- Has an active infection requiring systemic therapy

- Has a history of interstitial lung disease

- Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis

- Has an active autoimmune disease that has required systemic treatment in the past 2
years

- HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric
Castleman's Disease

- Has known Hepatitis B or C infection

- Has received prior systemic anticancer therapy, definitive radiotherapy, including
investigational agents within 4 weeks (2 weeks for palliative radiation) prior to the
first dose of study treatment

- Has not recovered from all radiation-related toxicities to Grade 1 or less

- Surgeries that required general anesthesia must be completed =2 weeks before first
study treatment administration. Surgery requiring regional/epidural anesthesia must be
completed =72 hours before first study treatment

- Has received a live vaccine within 30 days prior to the first dose of study treatment

- Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 28 days prior to the first dose of
study treatment.

- 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 treatment

- 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 tissue/solid organ transplant in the last 5 years or has
evidence of graft-versus-host disease

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
Other
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
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)
VIC
Recruitment hospital [1] 0 0
Alfred Health ( Site 0031) - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Michigan
Country [2] 0 0
United States of America
State/province [2] 0 0
New Jersey
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
Canada
State/province [4] 0 0
British Columbia
Country [5] 0 0
Canada
State/province [5] 0 0
Ontario
Country [6] 0 0
Israel
State/province [6] 0 0
Ramat Gan

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

Ethics approval
Ethics application status

Summary
Brief summary
This is a dose escalation study to determine the safety and pharmacokinetics of MK-0482 as
monotherapy and in combination with pembrolizumab (MK-3475) in participants with advanced
solid tumors for which there is no available therapy which may convey clinical benefit.
Trial website
https://clinicaltrials.gov/show/NCT03918278
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/NCT03918278