Relative Bioavailability Study of Subcutaneous Injection Versus Intravenous Infusion of Pembrolizumab (MK-3475) in Participants With Advanced Melanoma (MK-3475-555/KEYNOTE-555)
Melanoma
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
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
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Pembrolizumab Sequence 1
Pembrolizumab Sequence 2
Pembrolizumab Sequence 3
Pembrolizumab Sequence 4
Pembrolizumab Sequence 5
Pembrolizumab Sequence 6
Pembrolizumab Dose D
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).