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Report for Clinical Trial NCT02178722

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of MK-3475 in Combination With INCB024360 in Subjects With Selected Cancers (ECHO-202/KEYNOTE-037)

The purpose of this study was to assess the safety, tolerability, and efficacy when combining MK-3475 and INCB024360 in participants with certain cancers. This study was conducted in 2 phases, Phase 1 and Phase 2.

NCT02178722 Microsatellite-instability (MSI) High Colorectal Cancer (CRC) Endometrial Cancer Head and Neck Cancer Hepatocellular Carcinoma (HCC) Gastric Cancer Lung Cancer Lymphoma Renal Cell Carcinoma (RCC) Ovarian Cancer Solid Tumors UC (Urothelial Cancer) Melanoma Bladder Cancer Triple Negative Breast Cancer (TNBC)
MeSH: Carcinoma Carcinoma, Hepatocellular Carcinoma, Renal Cell Endometrial Neoplasms Triple Negative Breast Neoplasms Microsatellite Instability
HPO: Carcinoma Clear cell renal cell carcinoma Endometrial carcinoma Hepatocellular carcinoma Papillary renal cell carcinoma Renal cell carcinoma

2 Interventions

Name: MK-3475

Description: IV infusion

Type: Drug

Phase 1: MK-3475 + INCB024360 Phase 2: MK-3475 + INCB024360

Name: INCB024360

Description: Oral daily dosing

Type: Drug

Phase 1: MK-3475 + INCB024360 Phase 2: MK-3475 + INCB024360


Primary Outcomes

Description: An adverse event is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after a participant provides informed consent. A TEAE is any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug. Serious adverse event (SAE) is defined as an event that meets 1 of the following criteria: is fatal or life threatening, results in persistent or significant disability or incapacity, constitutes a congenital anomaly or birth defect, is clinically meaningful (i.e. defined as an event that jeopardizes the participant or requires potential medical or surgical intervention to prevent 1 of the outcomes listed above) or requires inpatient hospitalization or prolongation of existing hospitalization.

Measure: Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events

Time: From study start up to clinical data cut-off date of 26 Nov 2018 (approximately 54 months)

Description: ORR was proportion of participants with best overall response [complete response (CR) or partial response (PR)], per modified Response Evaluation Criteria In Solid Tumors (irRECIST) v1.1 criteria for select solid tumors or modified Lugano Classification for diffuse large B-cell lymphoma (DLBCL).

Measure: Phase 2: Objective Response Rate (ORR)

Time: Assessed every 9 weeks after the first dose of study treatment for the first 2 assessments (Weeks 9 and 18) then every 12 weeks thereafter until data cut-off date of 26 Nov 2018 (approximately 54 months)

Secondary Outcomes

Description: Duration of response is the time from the first overall response contributing to an objective response (complete response or partial response) to the date of death or the date of first overall response of progressive disease (whichever is earliest).

Measure: Phase 2: Duration of Response (DOR)

Time: Assessed every 9 weeks for duration of study participation which is estimated to be a minimum of 18 weeks

Description: Progression-free survival is defined as number of days from the first day of taking study drug to the earlier of death or disease progression by irRECIST v1.1 for select solid tumors and modified Lugano Classification (Cheson et al 2014) for DLBCL.

Measure: Phase 2: Progression Free Survival (PFS)

Time: Response is measured every 9 weeks for duration of study participation which is estimated to be a minimum of 18 weeks

Description: The duration of disease control is the time from the treatment start date to the first objective response of PD (by irRECIST v1.1 or Lugano Classification Cheson et al 2014), death, or last tumor assessment date (if PD/death not present), for subjects with best overall response of SD or bette

Measure: Phase 2: Duration of Disease Control

Time: Assessed every 9 weeks for duration of study participation which is estimated to be a minimum of 18 weeks

Description: Ordinal categorical response score, determined by radiographic disease assessments per irRECIST v1.1. The 5-category ordinal response endpoint is determined at a given timepoint by classifying response into one of the following groups: = Complete response per irRECIST v1.1 = Very good response, defined as > 60% tumor reduction = Minor response, defined as > 30% to ≤ 60% tumor reduction = Stable disease per irRECIST v1.1 = Progressive disease per irRECIST v1.1

Measure: Phase 2: Ordinal Categorical Response Score

Time: Assessed every 9 weeks for duration of study participation which is estimated to be a minimum of 18 weeks

Description: Overall survival is determined from the date of first dose until death due to any cause.

Measure: Phase 2: Overall Survival (OS)

Time: Patients are checked for survival every 12 weeks for duration of study participation which is estimated to be a minimum of 18 weeks

Measure: Phase 2: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events

Time: Adverse events are assessed every 3 weeks for duration of study participation which is estimated to be 27 months

Purpose: Treatment

Allocation: Non-Randomized

Parallel Assignment


There is one SNP

SNPs


1 V600E

- Phase 2 expansion: Melanoma - Documentation of V600E-activating BRAF mutation status. --- V600E ---



HPO Nodes


HPO:
Carcinoma
Genes 16
POLE MSH2 DKC1 SMARCA4 NLRP1 POLD1 CDKN1B MLH1 RSPO1 FGFR3 BCL10 APC STK11 PTEN APC KIT
Clear cell renal cell carcinoma
Genes 1
NOD2
Endometrial carcinoma
Genes 23
PMS2 SDHB CDH1 GREM1 POLD1 NTHL1 MSH6 BMPR1A POLE SDHC KLLN MSH2 MSH6 SDHD SEC23B MSH6 PTEN MLH1 POLD1 PIK3CA MLH3 AKT1 MSH3
Hepatocellular carcinoma
Genes 65
AHCY CTNNB1 CASP10 IGF2R JAG1 CASP8 HFE BMP2 HFE MLH1 PMS2 POU2AF1 HMBS FAH MSH6 SLC25A13 RASGRP1 EPCAM UROD AXIN1 TCF4 TP53 IL12A PRKCD SLC37A4 TGFBR2 SEMA4A JAK2 FAN1 FAS BMPR1A FAS KRAS FAH SPIB MSH2 HMBS MST1 MLH3 G6PC SPRTN SLC37A4 PIK3CA PDGFRL SERPINA1 TNFSF15 ATP7B IGF2 ABCB11 FASLG IL12RB1 SLC25A13 IRF5 RPS20 MET PIK3CA MMEL1 HFE H19 PMS1 F5 GPR35 APC TJP2 TNPO3
Papillary renal cell carcinoma
Genes 8
MET LMNA MINPP1 FOXE1 CDC73 FH HABP2 PRCC
Renal cell carcinoma
Genes 75
CCND1 TSC2 COL14A1 VHL HNF1B MET FLCN AKT1 SDHC HABP2 SDHAF2 NRAS FLCN SRC CDC73 FH APC PRCC SLC49A4 STK11 SDHB DCC TSC1 KLLN HNF1B SLC25A11 TP53 SDHD SEC23B BAP1 PTEN HNF1A KIF1B MAX PIK3CA VHL RNF139 MINPP1 CTNNB1 BUB1 RET KEAP1 DICER1 AAGAB DLC1 FN1 PIK3CA NOD2 SDHC FGFR3 FH TMEM127 VHL FLCN VHL OGG1 EP300 FOXE1 SDHB BUB1B AXIN2 SDHA MITF SDHD TFE3 FH IFNG PTPRJ LMNA HNF4A DLST MDH2 SDHB AKT1 FLCN