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Relative Bioavailability Study of Subcutaneous Injection Versus Intravenous Infusion of Pembrolizumab (MK-3475) in Participants With Advanced Melanoma (MK-3475-555/KEYNOTE-555)

Primary Purpose

Melanoma

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Pembrolizumab Dose C
Pembrolizumab Dose A
Pembrolizumab Dose B
Pembrolizumab Dose D
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma focused on measuring Programmed Cell Death 1, PD1, PD-1, Programmed Cell Death-Ligand 1, PDL1, PD-L1

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Has histologically or cytologically confirmed diagnosis of advanced melanoma.
  • Has unresectable Stage III or Stage IV melanoma, as per American Joint Committee on Cancer (AJCC) staging system not amenable to local therapy.
  • Has been untreated for advanced or metastatic disease except as follows:
  • a. BRAF V600 mutant melanoma may have received standard of care targeted therapy (e.g. BRAF/ mitogen-activated protein kinase kinase enzyme [MEK] inhibitor, alone or in combination) and be eligible for this study.
  • b. Prior adjuvant (post-surgery) or neoadjuvant (pre-surgery) melanoma therapy is permitted if it was completed ≥4 weeks before randomization and all related AEs have either returned to baseline or stabilized (resolution of toxic effect[s] of the most recent prior therapy to Grade 1 or less [except alopecia]).
  • Female participants must agree to use contraception during the treatment period and for ≥120 days after the last dose of study treatment.
  • Has measurable disease per RECIST 1.1 as assessed by BICR. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  • Has adequate organ function.

Exclusion Criteria:

  • Has received prior systemic treatment for unresectable or metastatic melanoma (exceptions as noted above in the Inclusion Criteria).
  • Has received prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. OX-40 and CD137) or any other antibody or drug specifically targeting checkpoint pathways other than anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) which is permitted in the adjuvant setting.
  • Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
  • 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 4 weeks prior to the first dose of study treatment.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment.
  • Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
  • Has known active central nervous system metastases and/or carcinomatous meningitis.
  • Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
  • Has ocular melanoma.
  • Has an 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 has current pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has a known history of human immunodeficiency virus (HIV) infection.
  • Has a known history of Hepatitis B or known active Hepatitis C virus 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 allogenic tissue/solid organ transplant.

Sites / Locations

  • Orange Health Services ( Site 0004)
  • Calvary Mater Newcastle ( Site 0006)
  • Cairns and Hinterland Hospital and Health Service ( Site 0001)
  • Royal Adelaide Hospital ( Site 0002)
  • Ballarat Health Services ( Site 0003)
  • MNCCI Port Macquarie Base Hospital ( Site 0005)
  • MPOC ( Site 0027)
  • WITS Clinical Research CMJAH Clinical Trial Site ( Site 0030)
  • The Medical Oncology Centre of Rosebank ( Site 0026)
  • Cape Town Oncology Trials Pty Ltd ( Site 0028)
  • Sandton Oncology Medical Group PTY LTD ( Site 0029)
  • Hospital Universitari Vall d Hebron ( Site 0062)
  • Hospital Clinic i Provincial de Barcelona ( Site 0061)
  • Onkologikoa - Instituto Oncologico de San Sebastian ( Site 0063)
  • Karolinska Universitetssjukhuset Solna ( Site 0040)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Pembrolizumab Sequence 1

Pembrolizumab Sequence 2

Pembrolizumab Sequence 3

Pembrolizumab Sequence 4

Pembrolizumab Sequence 5

Pembrolizumab Sequence 6

Pembrolizumab Dose D

Arm Description

Participants receive a single dose of pembrolizumab (pembro) in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembro Dose A subcutaneously (SC); Cycle 2 Day 1: pembro Dose B intravenously (IV); Cycle 3 Day 1: pembro Dose C SC; Cycle 4 Day 1 and every cycle thereafter (up to a total of 35 cycles) Day 1: pembro Dose B IV.

Participants receive a single dose of pembro in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembro Dose A SC; Cycle 2 Day 1: pembro Dose C SC; Cycle 3 Day 1: pembro Dose B IV; Cycle 4 Day 1 and every cycle thereafter (up to a total of 35 cycles) Day 1: pembro Dose B IV.

Participants receive a single dose of pembro in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembro Dose C SC; Cycle 2 Day 1: pembro Dose A SC; Cycle 3 Day 1: pembro Dose B IV; Cycle 4 Day 1 and every cycle thereafter (up to a total of 35 cycles) Day 1: pembro Dose B IV.

Participants receive a single dose of pembro in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembro Dose C SC; Cycle 2 Day 1: pembro Dose B IV; Cycle 3 Day 1: pembro Dose A SC; Cycle 4 Day 1 and every cycle thereafter (up to a total of 35 cycles) Day 1: pembro Dose B IV.

Participants receive a single dose of pembro in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembro Dose B IV; Cycle 2 Day 1: pembro Dose C SC; Cycle 3 Day 1: pembro Dose A SC: Cycle 4 Day 1 and every cycle thereafter (up to a total of 35 cycles) Day 1: pembro Dose B IV.

Participants receive a single dose of pembro in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembro Dose B IV; Cycle 2 Day 1: pembro Dose A SC; Cycle 3 Day 1: pembro Dose C SC; Cycle 4 Day 1 and every cycle thereafter (up to a total of 35 cycles) Day 1: pembro Dose B IV.

Participants receive a single dose of pembro Dose D IV on Day 1 of each 42-day cycle (every 6 weeks; Q6W) for up to 18 cycles (up to approximately 2 years).

Outcomes

Primary Outcome Measures

Pembrolizumab Area Under the Concentration-Time Curve (AUC) - Pembrolizumab Sequence 1-6
Blood samples are to be collected at designated time points for the determination of the pembro AUC. (Time points for SC injection: Cycles 1-4: Day 1 Predose, and Days 2, 3, 4, 5, 6, 7, 10 and 15. Time points for IV Infusion: Cycles 1-4: Day 1 Predose; Cycles 1-3: Day 1 End of Infusion [~0.5 hours after start of infusion], and Days 2, 5, 10 and 15.) Each cycle is 21 days.
Pembrolizumab Maximum Plasma Concentration (Cmax) - Pembrolizumab Sequence 1-6
Blood samples are to be collected at designated time points for the determination of the pembro Cmax. (Time points for SC injection: Cycles 1-4: Day 1 Predose, and Days 2, 3, 4, 5, 6, 7, 10 and 15. Time points for IV Infusion: Cycles 1-4: Day 1 Predose; Cycles 1-3: Day 1 End of Infusion [~0.5 hours after start of infusion], and Days 2, 5, 10 and 15.) Each cycle is 21 days.
Pembrolizumab Bioavailability (F)
Blood samples are to be collected at designated time points for the determination of the pembro F. (Time points for SC injection: Cycles 1-4: Day 1 Predose, and Days 2, 3, 4, 5, 6, 7, 10 and 15. Time points for IV Infusion: Cycles 1-4: Day 1 Predose; Cycles 1-3: Day 1 End of Infusion [~0.5 hours after start of infusion], and Days 2, 5, 10 and 15.) Each cycle is 21 days.
Pembrolizumab Absorption Rate (Ka)
Blood samples are to be collected at designated time points for the determination of the pembro Ka. (Time points for SC injection: Cycles 1-4: Day 1 Predose, and Days 2, 3, 4, 5, 6, 7, 10 and 15. Time points for IV Infusion: Cycles 1-4: Day 1 Predose; Cycles 1-3: Day 1 End of Infusion [~0.5 hours after start of infusion], and Days 2, 5, 10 and 15.) Each cycle is 21 days.
Pembrolizumab Time of Maximum Plasma Concentration (Tmax)
Blood samples are to be collected at designated time points for the determination of the pembro Tmax. (Time points for SC injection: Cycles 1-4: Day 1 Predose, and Days 2, 3, 4, 5, 6, 7, 10 and 15. Time points for IV Infusion: Cycles 1-4: Day 1 Predose; Cycles 1-3: Day 1 End of Infusion [~0.5 hours after start of infusion], and Days 2, 5, 10 and 15.) Each cycle is 21 days.
Pembrolizumab Clearance (CL)
Blood samples are to be collected at designated time points for the determination of the pembro CL. (Time points for SC injection: Cycles 1-4: Day 1 Predose, and Days 2, 3, 4, 5, 6, 7, 10 and 15. Time points for IV Infusion: Cycles 1-4: Day 1 Predose; Cycles 1-3: Day 1 End of Infusion [~0.5 hours after start of infusion], and Days 2, 5, 10 and 15.) Each cycle is 21 days.
Pembrolizumab Central Volume of Distribution (Vc)
Blood samples are to be collected at designated time points for the determination of the pembro Vc. (Time points for SC injection: Cycles 1-4: Day 1 Predose, and Days 2, 3, 4, 5, 6, 7, 10 and 15. Time points for IV Infusion: Cycles 1-4: Day 1 Predose; Cycles 1-3: Day 1 End of Infusion [~0.5 hours after start of infusion], and Days 2, 5, 10 and 15.) Each cycle is 21 days.
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab Dose D Only
ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions). Responses are based upon blinded independent central review (BICR) per RECIST 1.1. ORR will be presented.

Secondary Outcome Measures

Pembrolizumab Anti-drug Antibody Levels: Cycles 1-4 of Pembrolizumab SC Treatment - SC Injections Only
Blood samples are to be collected at designated time points for the determination of the presence or absence of pembrolizumab anti-drug antibodies. The percentage of participants who develop anti-pembrolizumab antibodies will be presented.
Adverse Events (AEs): Cycles 1-3
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants who experience an AE during Cycles 1-3 will be presented.
Study Treatment Discontinuations Due to an AE: Cycles 1-3
The percentage of participants who discontinue study treatment due to an AE during Cycles 1-3 will be presented.
Injection Site Signs and Symptoms: Cycles 1-3 of Pembrolizumab - SC Injection Only
Within 60 minutes after each pembrolizumab SC injection during Cycles 1-3, participants are to complete the Injection Site Signs and Symptoms Questionnaire. Participants are asked to rate any pain, itching, swelling and redness they experience at the pembrolizumab SC injection site from "None" to "Severe". The percentage of participants who experience an injection site sign or symptom will be presented.
Duration of Response (DOR) Per RECIST 1.1 - Pembrolizumab Dose D Only
For participants who demonstrate a CR or PR, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death. DOR will be calculated for RECIST 1.1 based on BICR. DOR for Pembrolizumab Dose D only will be presented.
Progression-free Survival (PFS) Per to RECIST v1.1 Modified to Follow a Maximum of 10 Target Lesions and a Maximum of 5 Target Lesions Per Organ - Pembrolizumab Dose D Only
PFS is defined as the time from the first dose of study treatment to the first documented disease progression per RECIST 1.1 based on BICR or death due to any cause, whichever occurs first. Although RECIST 1.1 references a maximum of 5 target lesions in total and 2 per organ, this protocol allows for a maximum of 10 target lesions in total and 5 per organ. PFS for Pembrolizumab Dose D only will be presented.
Overall Survival (OS) - Pembrolizumab Dose D Only
OS is defined as the time from the first dose of study treatment to death due to any cause. OS for Pembrolizumab Dose D only will be presented.
Pembrolizumab AUC - Pembrolizumab Dose D Only
Blood samples are to be collected at designated time points for the determination of the pembrolizumab AUC in participants receiving Pembrolizumab Dose D only.
Pembrolizumab Cmax - Pembrolizumab Dose D Only
Blood samples are to be collected at designated time points for the determination of the pembrolizumab Cmax in participants receiving Pembrolizumab Dose D only.
Pembrolizumab Minimum Plasma Concentration (Cmin) - Pembrolizumab Dose D Only
Blood samples are to be collected at designated time points for the determination of the pembrolizumab Cmin in participants receiving Pembrolizumab Dose D only.

Full Information

First Posted
August 23, 2018
Last Updated
January 19, 2023
Sponsor
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT03665597
Brief Title
Relative Bioavailability Study of Subcutaneous Injection Versus Intravenous Infusion of Pembrolizumab (MK-3475) in Participants With Advanced Melanoma (MK-3475-555/KEYNOTE-555)
Official Title
A Phase 1 Randomized Clinical Study of Pembrolizumab (MK-3475) to Evaluate the Relative Bioavailability of Subcutaneous Injection Versus Intravenous Infusion in Participants With Advanced Melanoma (KEYNOTE-555)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 19, 2018 (Actual)
Primary Completion Date
December 4, 2023 (Anticipated)
Study Completion Date
December 4, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to characterize the pharmacokinetic (PK) profile of pembrolizumab (MK-3475) following single subcutaneous (SC) injection of pembrolizumab Dose A versus pembrolizumab Dose C in adults with advanced melanoma. Additionally, the safety and tolerability of pembrolizumab SC injections will be assessed. And, finally, the efficacy of pembrolizumab intravenous (IV) infusion administration will be assessed.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
Keywords
Programmed Cell Death 1, PD1, PD-1, Programmed Cell Death-Ligand 1, PDL1, PD-L1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
136 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Pembrolizumab Sequence 1
Arm Type
Experimental
Arm Description
Participants receive a single dose of pembrolizumab (pembro) in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembro Dose A subcutaneously (SC); Cycle 2 Day 1: pembro Dose B intravenously (IV); Cycle 3 Day 1: pembro Dose C SC; Cycle 4 Day 1 and every cycle thereafter (up to a total of 35 cycles) Day 1: pembro Dose B IV.
Arm Title
Pembrolizumab Sequence 2
Arm Type
Experimental
Arm Description
Participants receive a single dose of pembro in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembro Dose A SC; Cycle 2 Day 1: pembro Dose C SC; Cycle 3 Day 1: pembro Dose B IV; Cycle 4 Day 1 and every cycle thereafter (up to a total of 35 cycles) Day 1: pembro Dose B IV.
Arm Title
Pembrolizumab Sequence 3
Arm Type
Experimental
Arm Description
Participants receive a single dose of pembro in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembro Dose C SC; Cycle 2 Day 1: pembro Dose A SC; Cycle 3 Day 1: pembro Dose B IV; Cycle 4 Day 1 and every cycle thereafter (up to a total of 35 cycles) Day 1: pembro Dose B IV.
Arm Title
Pembrolizumab Sequence 4
Arm Type
Experimental
Arm Description
Participants receive a single dose of pembro in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembro Dose C SC; Cycle 2 Day 1: pembro Dose B IV; Cycle 3 Day 1: pembro Dose A SC; Cycle 4 Day 1 and every cycle thereafter (up to a total of 35 cycles) Day 1: pembro Dose B IV.
Arm Title
Pembrolizumab Sequence 5
Arm Type
Experimental
Arm Description
Participants receive a single dose of pembro in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembro Dose B IV; Cycle 2 Day 1: pembro Dose C SC; Cycle 3 Day 1: pembro Dose A SC: Cycle 4 Day 1 and every cycle thereafter (up to a total of 35 cycles) Day 1: pembro Dose B IV.
Arm Title
Pembrolizumab Sequence 6
Arm Type
Experimental
Arm Description
Participants receive a single dose of pembro in each 21-day cycle in the following sequence: Cycle 1 Day 1: pembro Dose B IV; Cycle 2 Day 1: pembro Dose A SC; Cycle 3 Day 1: pembro Dose C SC; Cycle 4 Day 1 and every cycle thereafter (up to a total of 35 cycles) Day 1: pembro Dose B IV.
Arm Title
Pembrolizumab Dose D
Arm Type
Experimental
Arm Description
Participants receive a single dose of pembro Dose D IV on Day 1 of each 42-day cycle (every 6 weeks; Q6W) for up to 18 cycles (up to approximately 2 years).
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab Dose C
Other Intervention Name(s)
MK-3475
Intervention Description
SC injection
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab Dose A
Other Intervention Name(s)
MK-3475
Intervention Description
SC injection
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab Dose B
Other Intervention Name(s)
MK-3475
Intervention Description
IV infusion
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab Dose D
Other Intervention Name(s)
MK-3475
Intervention Description
IV infusion once every 6 weeks
Primary Outcome Measure Information:
Title
Pembrolizumab Area Under the Concentration-Time Curve (AUC) - Pembrolizumab Sequence 1-6
Description
Blood samples are to be collected at designated time points for the determination of the pembro AUC. (Time points for SC injection: Cycles 1-4: Day 1 Predose, and Days 2, 3, 4, 5, 6, 7, 10 and 15. Time points for IV Infusion: Cycles 1-4: Day 1 Predose; Cycles 1-3: Day 1 End of Infusion [~0.5 hours after start of infusion], and Days 2, 5, 10 and 15.) Each cycle is 21 days.
Time Frame
At designated time points (Up to approximately 78 days)
Title
Pembrolizumab Maximum Plasma Concentration (Cmax) - Pembrolizumab Sequence 1-6
Description
Blood samples are to be collected at designated time points for the determination of the pembro Cmax. (Time points for SC injection: Cycles 1-4: Day 1 Predose, and Days 2, 3, 4, 5, 6, 7, 10 and 15. Time points for IV Infusion: Cycles 1-4: Day 1 Predose; Cycles 1-3: Day 1 End of Infusion [~0.5 hours after start of infusion], and Days 2, 5, 10 and 15.) Each cycle is 21 days.
Time Frame
At designated time points (Up to approximately 78 days)
Title
Pembrolizumab Bioavailability (F)
Description
Blood samples are to be collected at designated time points for the determination of the pembro F. (Time points for SC injection: Cycles 1-4: Day 1 Predose, and Days 2, 3, 4, 5, 6, 7, 10 and 15. Time points for IV Infusion: Cycles 1-4: Day 1 Predose; Cycles 1-3: Day 1 End of Infusion [~0.5 hours after start of infusion], and Days 2, 5, 10 and 15.) Each cycle is 21 days.
Time Frame
At designated time points (Up to approximately 78 days)
Title
Pembrolizumab Absorption Rate (Ka)
Description
Blood samples are to be collected at designated time points for the determination of the pembro Ka. (Time points for SC injection: Cycles 1-4: Day 1 Predose, and Days 2, 3, 4, 5, 6, 7, 10 and 15. Time points for IV Infusion: Cycles 1-4: Day 1 Predose; Cycles 1-3: Day 1 End of Infusion [~0.5 hours after start of infusion], and Days 2, 5, 10 and 15.) Each cycle is 21 days.
Time Frame
At designated time points (Up to approximately 78 days)
Title
Pembrolizumab Time of Maximum Plasma Concentration (Tmax)
Description
Blood samples are to be collected at designated time points for the determination of the pembro Tmax. (Time points for SC injection: Cycles 1-4: Day 1 Predose, and Days 2, 3, 4, 5, 6, 7, 10 and 15. Time points for IV Infusion: Cycles 1-4: Day 1 Predose; Cycles 1-3: Day 1 End of Infusion [~0.5 hours after start of infusion], and Days 2, 5, 10 and 15.) Each cycle is 21 days.
Time Frame
At designated time points (Up to approximately 78 days)
Title
Pembrolizumab Clearance (CL)
Description
Blood samples are to be collected at designated time points for the determination of the pembro CL. (Time points for SC injection: Cycles 1-4: Day 1 Predose, and Days 2, 3, 4, 5, 6, 7, 10 and 15. Time points for IV Infusion: Cycles 1-4: Day 1 Predose; Cycles 1-3: Day 1 End of Infusion [~0.5 hours after start of infusion], and Days 2, 5, 10 and 15.) Each cycle is 21 days.
Time Frame
At designated time points (Up to approximately 78 days)
Title
Pembrolizumab Central Volume of Distribution (Vc)
Description
Blood samples are to be collected at designated time points for the determination of the pembro Vc. (Time points for SC injection: Cycles 1-4: Day 1 Predose, and Days 2, 3, 4, 5, 6, 7, 10 and 15. Time points for IV Infusion: Cycles 1-4: Day 1 Predose; Cycles 1-3: Day 1 End of Infusion [~0.5 hours after start of infusion], and Days 2, 5, 10 and 15.) Each cycle is 21 days.
Time Frame
At designated time points (Up to approximately 78 days)
Title
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab Dose D Only
Description
ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions). Responses are based upon blinded independent central review (BICR) per RECIST 1.1. ORR will be presented.
Time Frame
Up to approximately 2 years
Secondary Outcome Measure Information:
Title
Pembrolizumab Anti-drug Antibody Levels: Cycles 1-4 of Pembrolizumab SC Treatment - SC Injections Only
Description
Blood samples are to be collected at designated time points for the determination of the presence or absence of pembrolizumab anti-drug antibodies. The percentage of participants who develop anti-pembrolizumab antibodies will be presented.
Time Frame
Cycles 1-4 Day 1: Predose. Each cycle is 21 days. (Up to approximately 64 days)
Title
Adverse Events (AEs): Cycles 1-3
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants who experience an AE during Cycles 1-3 will be presented.
Time Frame
Through Cycle 3 Day 21; Serious AEs: Through 90 days after end of treatment on Cycle 3 Day 1. Each cycle is 21 days. (Up to approximately 133 days)
Title
Study Treatment Discontinuations Due to an AE: Cycles 1-3
Description
The percentage of participants who discontinue study treatment due to an AE during Cycles 1-3 will be presented.
Time Frame
Through Cycle 3 Day 1. Each cycle is 21 days. (Up to approximately 43 days)
Title
Injection Site Signs and Symptoms: Cycles 1-3 of Pembrolizumab - SC Injection Only
Description
Within 60 minutes after each pembrolizumab SC injection during Cycles 1-3, participants are to complete the Injection Site Signs and Symptoms Questionnaire. Participants are asked to rate any pain, itching, swelling and redness they experience at the pembrolizumab SC injection site from "None" to "Severe". The percentage of participants who experience an injection site sign or symptom will be presented.
Time Frame
Cycles 1-3 Day 1: Up to 60 minutes postdose. Each cycle is 21 days. (Up to approximately 43 days)
Title
Duration of Response (DOR) Per RECIST 1.1 - Pembrolizumab Dose D Only
Description
For participants who demonstrate a CR or PR, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death. DOR will be calculated for RECIST 1.1 based on BICR. DOR for Pembrolizumab Dose D only will be presented.
Time Frame
Up to approximately 2 years
Title
Progression-free Survival (PFS) Per to RECIST v1.1 Modified to Follow a Maximum of 10 Target Lesions and a Maximum of 5 Target Lesions Per Organ - Pembrolizumab Dose D Only
Description
PFS is defined as the time from the first dose of study treatment to the first documented disease progression per RECIST 1.1 based on BICR or death due to any cause, whichever occurs first. Although RECIST 1.1 references a maximum of 5 target lesions in total and 2 per organ, this protocol allows for a maximum of 10 target lesions in total and 5 per organ. PFS for Pembrolizumab Dose D only will be presented.
Time Frame
Up to approximately 2 years
Title
Overall Survival (OS) - Pembrolizumab Dose D Only
Description
OS is defined as the time from the first dose of study treatment to death due to any cause. OS for Pembrolizumab Dose D only will be presented.
Time Frame
Up to approximately 2 years
Title
Pembrolizumab AUC - Pembrolizumab Dose D Only
Description
Blood samples are to be collected at designated time points for the determination of the pembrolizumab AUC in participants receiving Pembrolizumab Dose D only.
Time Frame
At designated time points (Up to approximately 7 months)
Title
Pembrolizumab Cmax - Pembrolizumab Dose D Only
Description
Blood samples are to be collected at designated time points for the determination of the pembrolizumab Cmax in participants receiving Pembrolizumab Dose D only.
Time Frame
At designated time points (Up to approximately 7 months)
Title
Pembrolizumab Minimum Plasma Concentration (Cmin) - Pembrolizumab Dose D Only
Description
Blood samples are to be collected at designated time points for the determination of the pembrolizumab Cmin in participants receiving Pembrolizumab Dose D only.
Time Frame
At designated time points (Up to approximately 7 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Has histologically or cytologically confirmed diagnosis of advanced melanoma. Has unresectable Stage III or Stage IV melanoma, as per American Joint Committee on Cancer (AJCC) staging system not amenable to local therapy. Has been untreated for advanced or metastatic disease except as follows: a. BRAF V600 mutant melanoma may have received standard of care targeted therapy (e.g. BRAF/ mitogen-activated protein kinase kinase enzyme [MEK] inhibitor, alone or in combination) and be eligible for this study. b. Prior adjuvant (post-surgery) or neoadjuvant (pre-surgery) melanoma therapy is permitted if it was completed ≥4 weeks before randomization and all related AEs have either returned to baseline or stabilized (resolution of toxic effect[s] of the most recent prior therapy to Grade 1 or less [except alopecia]). Female participants must agree to use contraception during the treatment period and for ≥120 days after the last dose of study treatment. Has measurable disease per RECIST 1.1 as assessed by BICR. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Has adequate organ function. Exclusion Criteria: Has received prior systemic treatment for unresectable or metastatic melanoma (exceptions as noted above in the Inclusion Criteria). Has received prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. OX-40 and CD137) or any other antibody or drug specifically targeting checkpoint pathways other than anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) which is permitted in the adjuvant setting. Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. 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 4 weeks prior to the first dose of study treatment. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment. Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. Has known active central nervous system metastases and/or carcinomatous meningitis. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients. Has ocular melanoma. Has an 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 has current pneumonitis. Has an active infection requiring systemic therapy. Has a known history of human immunodeficiency virus (HIV) infection. Has a known history of Hepatitis B or known active Hepatitis C virus 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 allogenic tissue/solid organ transplant.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
Orange Health Services ( Site 0004)
City
Orange
State/Province
New South Wales
ZIP/Postal Code
2800
Country
Australia
Facility Name
Calvary Mater Newcastle ( Site 0006)
City
Waratah
State/Province
New South Wales
ZIP/Postal Code
2298
Country
Australia
Facility Name
Cairns and Hinterland Hospital and Health Service ( Site 0001)
City
Cairns
State/Province
Queensland
ZIP/Postal Code
4870
Country
Australia
Facility Name
Royal Adelaide Hospital ( Site 0002)
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Ballarat Health Services ( Site 0003)
City
Ballarat
ZIP/Postal Code
3350
Country
Australia
Facility Name
MNCCI Port Macquarie Base Hospital ( Site 0005)
City
Port Macquarie
ZIP/Postal Code
2444
Country
Australia
Facility Name
MPOC ( Site 0027)
City
Groenkloof Pretoria
State/Province
Gauteng
ZIP/Postal Code
0181
Country
South Africa
Facility Name
WITS Clinical Research CMJAH Clinical Trial Site ( Site 0030)
City
Johannesburg
State/Province
Gauteng
ZIP/Postal Code
2193
Country
South Africa
Facility Name
The Medical Oncology Centre of Rosebank ( Site 0026)
City
Johannesburg
State/Province
Gauteng
ZIP/Postal Code
2196
Country
South Africa
Facility Name
Cape Town Oncology Trials Pty Ltd ( Site 0028)
City
Kraaifontein
State/Province
Western Cape
ZIP/Postal Code
7570
Country
South Africa
Facility Name
Sandton Oncology Medical Group PTY LTD ( Site 0029)
City
Johannesburg
ZIP/Postal Code
2196
Country
South Africa
Facility Name
Hospital Universitari Vall d Hebron ( Site 0062)
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clinic i Provincial de Barcelona ( Site 0061)
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Onkologikoa - Instituto Oncologico de San Sebastian ( Site 0063)
City
San Sebastian
ZIP/Postal Code
20014
Country
Spain
Facility Name
Karolinska Universitetssjukhuset Solna ( Site 0040)
City
Solna
ZIP/Postal Code
171 64
Country
Sweden

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Links:
URL
http://merckoncologyclinicaltrials.com
Description
Merck Oncology Clinical Trials Information

Learn more about this trial

Relative Bioavailability Study of Subcutaneous Injection Versus Intravenous Infusion of Pembrolizumab (MK-3475) in Participants With Advanced Melanoma (MK-3475-555/KEYNOTE-555)

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