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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
Group Labels: 16

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
Group Labels: 7

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
Group Labels: 13

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: