Clinical trial NCT02180061: Study of Pembrolizumab (MK-3475) in Participants With Advanced Melanoma (MK-3475-041/KEYNOTE-041)
Official title: Phase Ib Study of MK-3475 in Subjects With Advanced Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Melanoma
Keywords: PD1
PD-1
PDL1
PD-L1
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2014-07-02
Enrollment: 42
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will assess the safety, tolerability, and efficacy of every-3-week dosing (Q3W) of pembrolizumab (MK-3475) in participants with advanced melanoma; participants may receive pembrolizumab for up to 2 years if deriving clinical benefit. The primary study hypothesis is that treatment with single agent pembrolizumab will result in a clinically meaningful overall response rate.

Detailed description: Participants who discontinue pembrolizumab after achieving a complete response (CR) and subsequently develop progressive disease (PD) may be eligible to enter a Second Course Phase and receive pembrolizumab again.

The end of the study for each participant will occur with: 1) the marketing approval of pembrolizumab for melanoma, 2) the completion of safety follow up or 3) the time when a possibility of entry to second course of treatment is lost, whichever occurs last.

Eligibility criteria: Inclusion criteria:

* Histologically confirmed diagnosis of locally advanced (unresectable Stage III) or metastatic (Stage IV) melanoma not amenable to local therapy
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* At least one measurable lesion
* Adequate organ function

Exclusion criteria:

* Prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-PD ligand-1 (PD-L1), anti-PD-L2, anti-CD137 antibody, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) agent
* Is currently participating or has participated in a study with an investigational compound or device within 30 days, or 5X half-life of the investigational compound, whichever is longer, of initial dosing on this study
* Chemotherapy, targeted small molecule therapy, radiotherapy, or biological cancer therapy (including monoclonal antibodies) within 4 weeks prior to the first dose of trial treatment, or not recovered (\<= Grade 1 or baseline) from adverse events due to a previously administered agent
* Expected to require any other form of systemic or localized antineoplastic therapy while in study
* Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents
* Receiving systemic steroid therapy or any other form of immunosuppressive therapy within 1 week prior to the first dose of study treatment
* Received a live vaccine within 4 weeks prior to the first dose of trial treatment
* Has a known hypersensitivity to the components of the study drug or another monoclonal antibody
* History or evidence of active pneumonitis
* Human immunodeficiency virus (HIV)-positive
* Has known history of active Hepatitis B or C
* Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial treatment through 120 days after the last dose of study medication

Primary outcomes:
measure: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: All AEs: Up to 30 days after last dose of study drug; Serious AEs: Up to 90 days after last dose of study drug (Up to 27 months)
measure: Number of Participants Discontinuing Treatment Due to AEs
timeFrame: Up to last dose of study drug (Up to 24 months)
measure: Overall Response Rate (ORR) Per Central Radiology Review Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
timeFrame: Up to 24 months
Secondary outcomes:
measure: ORR Per Investigator Assessment Using RECIST 1.1
timeFrame: Up to 24 months
measure: ORR Per Central Radiology Review Using Immune-related Response Criteria (irRC)
timeFrame: Up to 24 months
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Yamazaki N, Takenouchi T, Fujimoto M, Ihn H, Uchi H, Inozume T, Kiyohara Y, Uhara H, Nakagawa K, Furukawa H, Wada H, Noguchi K, Shimamoto T, Yokota K. Phase 1b study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced melanoma (KEYNOTE-041). Cancer Chemother Pharmacol. 2017 Apr;79(4):651-660. doi: 10.1007/s00280-016-3237-x. Epub 2017 Mar 11.