A Study of the Anti-PD1 Antibody PDR001, in Combination With Dabrafenib and Trametinib in Advanced Melanoma
The purpose of this study was to evaluate safety and efficacy of the combination of an anti-PD-1 antibody (PDR001), a BRAF inhibitor (dabrafenib) and a MEK inhibitor (trametinib) in patients with BRAF V600 mutant, unresectable and metastatic melanoma.
Inclusion Criteria
- Inclusion criteria Part 1: Safety run-in - Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation - Aspartate transaminase (AST) < 2.5× ULN and Alanine transaminase (ALT) < 2.5× ULN - Measurable disease according to RECIST 1.1 - ECOG performance status ≤ 1 Part 2: Biomarker cohort - Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation - At least two cutaneous or subcutaneous or nodal lesions for tumor sample collection - Measurable disease according to RECIST 1.1 - ECOG performance status ≤ 2 Part 3: Double-blind, randomized, placebo-controlled part - Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation - ECOG performance status ≤ 2 - Measurable disease according to RECIST 1.1 Exclusion Criteria: Part 1: Safety run-in - Subjects with uveal or mucosal melanoma - Any history of CNS metastases - Prior systemic anti-cancer treatment for unresectable or metastatic melanoma - Neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months prior to enrollmen - Radiation therapy within 4 weeks prior to start of study treatment - Active autoimmune disease, and/or history of autoimmune disease(s) that required treatment Parts 2 & 3: Biomarker cohort & double-blind, randomized, placebo-controlled part - Subjects with uveal or mucosal melanoma - Prior systemic anti-cancer treatment for unresectable or metastatic melanoma - Neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months prior to enrollment - Radiation therapy within 4 weeks prior to start of study treatment - Clinically active cerebral melanoma metastasis. - Active autoimmune disease, and/or history of autoimmune disease(s) that required treatment Other protocol-defined Inclusion/Exclusion may apply.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02967692.
Locations matching your search criteria
United States
Maryland
Baltimore
Pennsylvania
Pittsburgh
This study was designed as a phase III, multi-center study consisting of 3 parts:
- Part 1: Safety run-in part The safety run-in part aimed to determine the recommended
regimen of PDR001 in combination with dabrafenib and trametinib for previously
untreated patients with BRAF V600 mutant unresectable or metastatic melanoma (stage
IIIC/IV). Spartalizumab was administered at a starting dose level (DL1) of 400 mg
every 4 weeks (Q4W), along with fixed doses of dabrafenib (150 mg twice daily) and
trametinib (2 mg once daily). The RP3R for Part 3 was determined using the Bayesian
Logistic Regression Model (BLRM) with escalation with overdose control (EWOC)
criteria.
- Part 2: Biomarker cohort Part 2 was run to explore changes in the immune
microenvironment and biomarker modulations upon treatment with the combination of
dabrafenib, trametinib and PDR001. Part 2 started when the fourth subject in dose
level 1 (DL1) of Part 1 completed approximately 4 weeks of study treatment, and
fewer than 3 dose-limiting toxicities (DLTs) were observed. Participants in Part 2
received PDR001 (spartalizumab) at a dosage of 400 mg Q4W, in combination with
dabrafenib (150 mg BID) and trametinib (2 mg QD).
- Part 3: Double-blind, randomized, placebo-controlled part Part 3 was comparing the
efficacy and safety of spartalizumab in combination with dabrafenib and trametinib
to placebo in combination with dabrafenib and trametinib. Part 3 was initiated after
determining the RP3R for the combination of spartalizumab with dabrafenib and
trametinib in Part 1. Subjects were randomized in a 1:1 ratio to receive either the
RP3R dose of spartalizumab identified in Part 1 or placebo, along with dabrafenib
(150 mg BID) and trametinib (2 mg QD).
For all parts of the study, the treatment continued until the subject experiences any of
the following events: disease progression according to RECIST 1.1 as determined by the
Investigator, unacceptable toxicity, initiation of a new anti-neoplastic therapy,
pregnancy, withdrawal of consent, physician's decision, loss to follow-up, death, or
termination of the study by the Sponsor. Safety evaluations are conducted for all
subjects for up to 150 days after the last dose of spartalizumab/placebo (safety
follow-up period).
Subjects who discontinued study treatment without disease progression as per RECIST 1.1
continued with tumor assessments according to the protocol until documented disease
progression, withdrawal of consent, loss to follow-up, or death, regardless of the
initiation of new anti-neoplastic therapy (efficacy follow-up period).
Subjects entered the survival follow-up period after completing the safety follow-up
period or experiencing disease progression as per RECIST 1.1 or response criteria for
immunotherapy, whichever period is longer (survival follow-up period).
Trial PhasePhase III
Trial Typetreatment
Lead OrganizationNovartis Pharmaceuticals Corporation
- Primary IDCPDR001F2301
- Secondary IDsNCI-2017-00814, 2016-002794-35
- ClinicalTrials.gov IDNCT02967692