Ignite Creation Date:
2024-05-06 @ 9:21 AM
Last Modification Date:
2024-10-26 @ 12:13 PM
Study NCT ID:
NCT02967692
Status:
COMPLETED
Last Update Posted:
2024-06-18
First Post:
2016-11-16
Brief Title:
A Study of the Anti-PD1 Antibody PDR001 in Combination With Dabrafenib and Trametinib in Advanced Melanoma
Sponsor:
Novartis Pharmaceuticals
Organization:
Novartis
Study Overview
Official Title:
A Randomized Double-blind Placebo-controlled Phase III Study Comparing the Combination of PDR001 Dabrafenib and Trametinib Versus Placebo Dabrafenib and Trametinib in Previously Untreated Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma
Status:
COMPLETED
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
COMBI-i
Brief Summary:
To evaluate the safety and efficacy of the combination of an anti-PD-1 antibody Spartalizumab PDR001 a BRAF inhibitor dabrafenib and a MEK inhibitor trametinib in unresectable or metastatic BRAF V600 mutant melanoma
Detailed Description:
This study is designed as a Phase III multi-center study consisting of three parts
Part 1 known as the Safety Run-in is an open-label part aimed at determining the recommended Phase III regimen RP3R of spartalizumab in combination with dabrafenib and trametinib for previously untreated subjects with BRAF V600 mutant unresectable or metastatic melanoma Stage IIICIV per AJCC edition 7 In Part 1 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 referred to as the Biomarker Cohort is an open-label section focused on characterizing the kinetics of immune biomarkers and potential immune resistance mechanisms 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 receive PDR001 spartalizumab at a dosage of 400 mg Q4W in combination with dabrafenib 150 mg BID and trametinib 2 mg QD
Part 3 is a double-blind randomized placebo-controlled phase that compares 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 11 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 is continued until the subject experiences any of the following events disease progression according to RECIST 11 as determined by the Investigator unacceptable toxicity initiation of a new anti-neoplastic therapy pregnancy withdrawal of consent physicians 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 spartalizumabplacebo safety follow-up period
Subjects who discontinue study treatment without disease progression as per RECIST 11 continue 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 enter the survival follow-up period after completing the safety follow-up period or experiencing disease progression as per RECIST 11 or response criteria for immunotherapy whichever period is longer survival follow-up period
Part 1 known as the Safety Run-in is an open-label part aimed at determining the recommended Phase III regimen RP3R of spartalizumab in combination with dabrafenib and trametinib for previously untreated subjects with BRAF V600 mutant unresectable or metastatic melanoma Stage IIICIV per AJCC edition 7 In Part 1 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 referred to as the Biomarker Cohort is an open-label section focused on characterizing the kinetics of immune biomarkers and potential immune resistance mechanisms 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 receive PDR001 spartalizumab at a dosage of 400 mg Q4W in combination with dabrafenib 150 mg BID and trametinib 2 mg QD
Part 3 is a double-blind randomized placebo-controlled phase that compares 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 11 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 is continued until the subject experiences any of the following events disease progression according to RECIST 11 as determined by the Investigator unacceptable toxicity initiation of a new anti-neoplastic therapy pregnancy withdrawal of consent physicians 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 spartalizumabplacebo safety follow-up period
Subjects who discontinue study treatment without disease progression as per RECIST 11 continue 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 enter the survival follow-up period after completing the safety follow-up period or experiencing disease progression as per RECIST 11 or response criteria for immunotherapy whichever period is longer survival follow-up period
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2016-002794-35 | EUDRACT_NUMBER | None | None |