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Report for Clinical Trial NCT03207867

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase 2, Multi-center, Open Label Study of NIR178 in Combination With PDR001 in Patients With Selected Advanced Solid Tumors and Non-Hodgkin Lymphoma

The purpose of this phase 2 study is to evaluate the efficacy and safety of NIR178 in combination with PDR001 in multiple solid tumors and diffuse large B-cell lymphoma (DLBCL) and further explore schedule variations of NIR178 to optimize immune activation through inhibition of A2aR.

NCT03207867 NSCLC, Non Small Cell Lung Cancer RCC, Renal Cell Cancer Pancreatic Cancer Urothelial Cancer Head and Neck Cancer DLBCL, Diffused Large B Cell Lymphoma MSS, Microsatellite Stable Colon Cancer TNBC, Triple Negative Breast Cancer Melanoma
MeSH: Lymphoma Lymphoma, Non-Hodgkin Triple Negative Breast Neoplasms Carcinoma, Renal Cell
HPO: Clear cell renal cell carcinoma Lymphoma Non-Hodgkin lymphoma Papillary renal cell carcinoma Renal cell carcinoma

2 Interventions

Name: NIR178

Description: NIR178, a new, non-xanthine based compound, is a potent oral adenosine A2a receptor against antagonist being developed by Novartis.

Type: Drug

Japanese safety run-in part NIR178 + PDR001 NIR178 BID Intermittent + PDR001 Part 3

Name: PDR001

Description: PDR001 is a human monoclonal antibody (MAb) administered day 1 of each cycle

Type: Drug

Japanese safety run-in part NIR178 + PDR001 NIR178 BID Intermittent + PDR001 Part 3


Primary Outcomes

Description: Response assessed by RECIST v1.1 (for solid tumors) or Cheson (for DLBCL)

Measure: Determine the overall response rate

Time: Every 8 weeks for first 40 weeks

Description: Response assessed by RECIST v1.1 (for solid tumors) or Cheson (for DLBCL)

Measure: Determine the overall response rate

Time: Every 12 weeks after the first 40 weeks until disease progression or study discontinuation (an average of 6 months)

Description: Response assessed by RECIST v1.1 (for solid tumors) or Cheson (for DLBCL)

Measure: Determine the overall response rate

Time: Baseline

Secondary Outcomes

Description: Proportion of patients with a best overall response of CR or PR or SD

Measure: Determine the disease control rate (DCR)

Time: Baseline

Description: Time from first documented response to disease progression

Measure: Determine the duration of response (DoR)

Time: Baseline

Description: Time from start of treatment to date of death due to any reason

Measure: Determine the overall survival rate (OR)

Time: Every 12 weeks until end of study for at least 24 months from the start date of the study treatment

Description: Time from start of treatment to date of the first documented progression or death in months

Measure: Progression free survival (PFS)

Time: Baseline

Description: Type, frequency, and severity of AEs and SAEs; Frequency of dose interruptions, reductions and discontinuation, Dose intensity

Measure: Safety and tolerability of the NIR178 and PDR001 combination

Time: Date of consent to end of study (An average of 24 months)

Description: Change from baseline in TILs by immunohistochemistry (IHC) (such as CD8)

Measure: Characterize changes in the immune infiltrate in tumors

Time: Screening

Description: Presence and/or concentration of anti-PDR001 antibodies

Measure: Presence and/or concentration of anti-PDR001 antibodies

Time: Starting from the first dose of study treatment to Cycle 6 Day 1

Description: Plasma concentration time profiles of NIR178 and its metabolites

Measure: Pharmacokinetics: Area under plasma concentration versus time curve (AUC) (NIR178)

Time: Starting from the first dose of study treatment to Cycle 6 Day 1

Description: Plasma concentration time profiles of PDR001

Measure: Pharmacokinetics: Area under the plasma concentration versus time curve (AUC) (PDR001)

Time: End of treatment and as needed (an average of 6 months)

Description: Plasma concentration time profiles of NIR178

Measure: Plasma concentration Vs Time profiles (NIR178)

Time: End of treatment and as needed (an average of 6 months)

Description: Plasma concentration time profiles of PDR001

Measure: Plasma concentration Vs Time profiles (PDR001)

Time: End of treatment and as needed (an average of 6 months)

Description: Plasma concentration time profiles of NIR178

Measure: Peak plasma concentration- Cmax (NIR178)

Time: End of treatment and as needed (an average of 6 months)

Description: Plasma concentration time profiles of PDR001

Measure: Peak plasma concentration- Cmax (PDR001)

Time: End of treatment and as needed (an average of 6 months)

Description: Plasma concentration time profiles of NIR178

Measure: Time of maximum concentration observed- Tmax (NIR178)

Time: End of treatment and as needed (an average of 6 months)

Description: Plasma concentration time profiles of PDR001

Measure: Time of maximum concentration observed- Tmax (PDR001)

Time: End of treatment and as needed (an average of 6 months)

Description: Proportion of patients with a best overall response of CR or PR or SD

Measure: Determine the disease control rate (DCR)

Time: Every 8 weeks for first 40 weeks

Description: Proportion of patients with a best overall response of CR or PR or SD

Measure: Determine the disease control rate (DCR)

Time: Every 12 weeks after the first 40 weeks until disease progression

Description: Time from first documented response to disease progression

Measure: Determine the duration of response (DoR)

Time: Until study discontinuation (an average of 6 months)

Description: Time from first documented response to disease progression

Measure: Determine the duration of response (DoR)

Time: Every 8 weeks for first 40 weeks

Description: Time from start of treatment to date of the first documented progression or death in months

Measure: Progression free survival (PFS)

Time: Until study discontinuation (an average of 6 months)

Description: Time from start of treatment to date of the first documented progression or death in months

Measure: Progression free survival (PFS)

Time: Every 8 weeks for first 40 weeks

Description: Change from baseline in TILs by immunohistochemistry (IHC) (such as CD8)

Measure: Characterize changes in the immune infiltrate in tumors

Time: Cycle 6 Day 1

Description: Change from baseline in TILs by immunohistochemistry (IHC) (such as CD8)

Measure: Characterize changes in the immune infiltrate in tumors

Time: Cycle 1 Day 8

Description: Change from baseline in TILs by immunohistochemistry (IHC) (such as CD8)

Measure: Characterize changes in the immune infiltrate in tumors

Time: Cycle 3 Day 1

Description: Presence and/or concentration of anti-PDR001 antibodies

Measure: Presence and/or concentration of anti-PDR001 antibodies

Time: End of treatment and as needed (an average of 6 months)

Description: Plasma concentration time profiles of NIR178 and its metabolites

Measure: Pharmacokinetics: Area under plasma concentration versus time curve (AUC) (NIR178)

Time: End of treatment and as needed (an average of 6 months)

Description: Plasma concentration time profiles of NIR178

Measure: Plasma concentration Vs Time profiles (NIR178)

Time: Starting from the first dose of study treatment to Cycle 6 Day 1

Description: Plasma concentration time profiles of PDR001

Measure: Plasma concentration Vs Time profiles (PDR001)

Time: Starting from the first dose of study treatment to Cycle 6 Day 1

Description: Plasma concentration time profiles of NIR178

Measure: Peak plasma concentration- Cmax (NIR178)

Time: Starting from the first dose of study treatment to Cycle 6 Day 1

Description: Plasma concentration time profiles of PDR001

Measure: Peak plasma concentration- Cmax (PDR001)

Time: Starting from the first dose of study treatment to Cycle 6 Day 1

Description: Plasma concentration time profiles of NIR178

Measure: Time of maximum concentration observed- Tmax (NIR178)

Time: Starting from the first dose of study treatment to Cycle 6 Day 1

Description: Plasma concentration time profiles of PDR001

Measure: Time of maximum concentration observed- Tmax (PDR001)

Time: Starting from the first dose of study treatment to Cycle 6 Day 1

Description: Proportion of patients with a best overall response of CR or PR or SD

Measure: Determine the disease control rate (DCR)

Time: Until study discontinuation (an average of 6 months)

Description: Proportion of patients with a best overall response of CR or PR or SD

Measure: Determine the duration of response (DoR)

Time: Every 12 weeks after the first 40 weeks until disease progression

Description: Time from start of treatment to date of the first documented progression or death in months

Measure: Progression free survival (PFS)

Time: Every 12 weeks after the first 40 weeks until disease progression

Purpose: Treatment

Allocation: Non-Randomized

Parallel Assignment


There is one SNP

SNPs


1 T790M

- Patients with EGFR positive NSCLC with a T790M mutation must have progressed on osimertinib or discontinued due to toxicity. --- T790M ---



HPO Nodes


HPO:
Clear cell renal cell carcinoma
Genes 1
NOD2
Lymphoma
Genes 133
ATM KRAS CD19 IGH DDX41 BCL10 BIRC3 FOXP1 MS4A1 TP63 RAG1 LIG4 NFKB2 MSH6 TERC RECQL4 NTHL1 WIPF1 CTC1 LYST NOP10 RASGRP1 TNFRSF1B XRCC4 PRKCD NHP2 MAGT1 TNFRSF13B IGH RMRP RUNX1 CTLA4 DCLRE1C FAS ICOS RNF43 NSUN2 XIAP IL7R CASP10 BCL6 CDKN2A ATM IL2RG RTEL1 PARN NBN KIT TNFRSF13C TCF4 ICOS TNFSF12 CHEK2 USB1 CD19 CR2 NRAS MSH2 WAS BCL10 CASP10 MYD88 COL14A1 PRKCD TNFRSF13B MYC MDM2 SH2D1A CCND1 BCL10 CFTR CD27 PGM3 TCF4 CHD7 IGH LIG4 BLM BCL2 TET2 HLA-DRB1 PRSS1 NPM1 KIF11 ITK WRAP53 RAD54B TINF2 FAS DKC1 APC CD81 LIG4 BLM CD28 DKC1 AAGAB RAG2 TNFRSF1B MLH1 TNFRSF13C DNASE1L3 NFKB1 PMS2 ASXL1 IL2RG PRF1 PTEN MALT1 RAD54L CTLA4 CD28 PNP SRSF2 TNFSF12 STAT3 POLE ADA CR2 ADA FASLG PIK3R1 TP53 CTRC ZAP70 MYD88 RB1 RMRP SPINK1 TERT KLHDC8B NBN RHOH
Non-Hodgkin lymphoma
Genes 32
ATM FAS CASP10 CTLA4 FAS BCL10 CD28 BIRC3 FOXP1 TNFRSF1B MYC CCND1 ASXL1 ATM MALT1 CTLA4 CD28 SRSF2 KIT POLE IGH ADA TET2 FASLG PIK3R1 NTHL1 RASGRP1 TNFRSF1B PRKCD NBN RHOH IGH
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