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Report for Clinical Trial NCT02130466

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase I/II Study to Assess the Safety and Efficacy of MK-3475 in Combination With Trametinib and Dabrafenib in Subjects With Advanced Melanoma

This is a 5-part dose-finding and preliminary efficacy study of pembrolizumab (Pembro) + dabrafenib (D) + trametinib (T) for participants with advanced melanoma and solid tumors. Parts 1 and 2 are open-label to find and confirm the maximum tolerated dose (MTD)/maximum administered dose (MAD) for Pembro+D+T. The primary hypothesis (Parts 1 and 2) is that Pembro+D+T is sufficiently well-tolerated to permit clinical investigation. Part 3 is a double-blind study of Pembro+D+T versus placebo+D+T. The primary study hypothesis (Part 3 only) is that the Pembro+D+T improves progression-free survival (PFS) compared with placebo+D+T. Part 4 is nonrandomized and open-label and is designed to evaluate the safety and tolerability and identify the MTD or MAD of Pembro+T in participants who have v-raf murine sarcoma viral oncogene homolog B1 [BRAF] mutation-negative (without V600 E or K) melanoma or solid tumors [irrespective of BRAF status]. The primary hypothesis (Part 4) is that Pembro+T is sufficiently well-tolerated to permit clinical investigation. Part 5 will confirm the dose(s) identified in Part 4 in participants BRAF wild type [without V600E or K] melanoma or solid tumors [irrespective of BRAF status] and will further evaluate the safety and preliminary efficacy (Objective Response Rate [ORR]) of Pembro+T in participants who have BRAF wild type [without V600E or K] melanoma only. The primary hypotheses (Part 5) are that Pembro+T is sufficiently well-tolerated at the MTD/MAD to permit further clinical investigation and is effective in attaining objective responses based upon Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator review in participants who have melanoma without BRAF V600 E or K mutations. With Amendment 5 (21-Mar-2019), the Part 5 expansion cohort will not be pursued following the completion of Part 5 dose confirmation. Parts 1 and 2 of the study will also explore the MTD/MAD for open-label Pembro+T (for BRAF mutation-negative participants) concurrently with the Pembro+D+T arm; Pembro+D (for BRAF mutation-positive participants).

NCT02130466 Melanoma Solid Tumors
MeSH: Melanoma
HPO: Cutaneous melanoma Melanoma

3 Interventions

Name: Pembrolizumab

Description: IV infusion

Type: Biological

Pembro+D (Parts 1 Pembro+D (Parts 1 & Pembro+D (Parts 1 & 2) Pembro+D+T (Parts 1, 2 Pembro+D+T (Parts 1, 2 & Pembro+D+T (Parts 1, 2 & 3) Pembro+T (Parts 1 Pembro+T (Parts 1 & Pembro+T (Parts 1 & 2) Pembro+T Concurrent Dosing (Parts 4 Pembro+T Concurrent Dosing (Parts 4 & Pembro+T Concurrent Dosing (Parts 4 & 5) Pembro+T Intermittent Dosing (Parts 4 Pembro+T Intermittent Dosing (Parts 4 & Pembro+T Intermittent Dosing (Parts 4 & 5) Placebo+D+T (Part 3)

Name: Dabrafenib

Description: oral capsule

Type: Drug

Pembro+D (Parts 1 Pembro+D (Parts 1 & Pembro+D (Parts 1 & 2) Pembro+D+T (Parts 1, 2 Pembro+D+T (Parts 1, 2 & Pembro+D+T (Parts 1, 2 & 3) Placebo+D+T (Part 3)

Name: Trametinib

Description: oral tablet

Type: Drug

Pembro+D+T (Parts 1, 2 Pembro+D+T (Parts 1, 2 & Pembro+D+T (Parts 1, 2 & 3) Pembro+T (Parts 1 Pembro+T (Parts 1 & Pembro+T (Parts 1 & 2) Pembro+T Concurrent Dosing (Parts 4 Pembro+T Concurrent Dosing (Parts 4 & Pembro+T Concurrent Dosing (Parts 4 & 5) Pembro+T Intermittent Dosing (Parts 4 Pembro+T Intermittent Dosing (Parts 4 & Pembro+T Intermittent Dosing (Parts 4 & 5) Placebo+D+T (Part 3)


Primary Outcomes

Measure: Parts 1, 2, 4 and 5: Number of Participants with Dose-limiting Toxicities (DLTs)

Time: Up to 6 weeks (Cycle 1)

Measure: Part 2: Objective Response Rate (ORR) in Participants Without BRAF V600 E or K Mutations

Time: Up to approximately 4 years

Measure: Part 3: Progression-Free Survival (PFS) in Participants With BRAF V600 E or K Mutations

Time: Up to approximately 4 years

Secondary Outcomes

Measure: Part 1: Objective Response Rate (ORR) in Participants With BRAF V600 E or K Mutations

Time: Up to approximately 4 years

Measure: Part 2: Objective Response Rate (ORR) in Participants With BRAF V600 E or K Mutations

Time: Up to approximately 4 years

Measure: Part 3: Objective Response Rate (ORR) in Participants With BRAF V600 E or K Mutations

Time: Up to approximately 4 years

Measure: Part 3: Duration of Response (DOR) in Participants With BRAF V600 E or K Mutations

Time: Up to approximately 4 years

Measure: Part 3: Overall Survival (OS) in Participants With BRAF V600 E or K Mutations

Time: Up to approximately 4 years

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 V600E

Part 5 will confirm the dose(s) identified in Part 4 in participants BRAF wild type [without V600E or K] melanoma or solid tumors [irrespective of BRAF status] and will further evaluate the safety and preliminary efficacy (Objective Response Rate [ORR]) of Pembro+T in participants who have BRAF wild type [without V600E or K] melanoma only. --- V600E ---

Part 5 will confirm the dose(s) identified in Part 4 in participants BRAF wild type [without V600E or K] melanoma or solid tumors [irrespective of BRAF status] and will further evaluate the safety and preliminary efficacy (Objective Response Rate [ORR]) of Pembro+T in participants who have BRAF wild type [without V600E or K] melanoma only. --- V600E --- --- V600E ---



HPO Nodes


HPO:
Cutaneous melanoma
Genes 15
HRAS MITF CDKN2A BRAF NRAS NRAS WRN CDKN2A CXCR4 BAP1 POLH CDK4 ERCC3 XPC MC1R
Melanoma
Genes 98
MGMT NRAS POT1 NRAS XPA CTSC BRCA1 SDHC ERCC4 CXCR4 RAD51C CDKN2B ERCC3 XPC PALLD ERCC2 ERCC2 CHEK2 CDKN2A RAD51D GNAQ SDHD KRAS MBTPS2 BAP1 BAP1 CYSLTR2 RNF43 BAP1 CDKN2A PTPN11 CDK4 BRCA2 ERCC3 MITF TERF2IP ERCC4 CHEK2 BRCA1 TRPV3 POT1 OCA2 TERT CDKN2A AKT1 CDKN2A SF3B1 ERCC6 ERCC5 ERCC5 MDM2 BRCA2 BAP1 GNA11 ACD BRIP1 HRAS MRE11 BRAF TYR TP53 KLLN SEC23B PTEN PIK3CA XPA PERP MITF RAF1 BRAF POLH TP53 BARD1 NRAS SMAD4 RAD50 DDB2 ERCC2 NBN TERT MC1R SLC45A2 WRN PALB2 DDB2 PALB2 CDKN2A SDHB MC1R RAD51 TP53 XPC ERCC3 PTEN CDKN2A POLH CDK4 MC1R