SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03502330

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A Phase I/Ib Study of APX005M in Combination With Nivolumab and Cabiralizumab in Patients With Advanced Melanoma, Non-small Cell Lung Cancer or Renal Cell Carcinoma Whose Disease Has Progressed on Anti-PD- 1/PD-L1 Therapy

This trial is a phase 1/1b study to evaluate the safety, efficacy, and tolerability of APX005M in combination with nivolumab and cabiralizumab. The phase 1 dose escalation portion of the study will enroll patients with advanced solid tumors melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) in 6 cohorts to determine the recommended phase II dose (RP2D) of APX005M. The phase 1b dose expansion portion will study the triple drug combination separately in the three disease cohorts: melanoma, NSCLC, and RCC. Submitted on 3/29/2018; investigational new drug (IND) number is pending and will be added to the record once received.

NCT03502330 Advanced Melanoma Non-small Cell Lung Cancer Renal Cell Carcinoma
MeSH: Carcinoma Lung Neoplasms Carcinoma, Non-Small-Cell Lung Melanoma Carcinoma, Renal Cell
HPO: Carcinoma Clear cell renal cell carcinoma Cutaneous melanoma Melanoma Neoplasm of the lung Non-small cell lung carcinoma Papillary renal cell carcinoma Renal cell carcinoma

3 Interventions

Name: APX005M

Description: APX005M is a humanized Immunoglobulin G (IgG) 1 agonistic monoclonal antibody that binds cluster of differentiation (CD) 40. APX005M is administered by intravenous infusion.

Type: Drug

Cohort 1 Advanced Solid Tumors Cohort 2 Advanced Solid Tumors Cohort 3 Advanced Solid Tumors Cohort 4 Advanced Solid Tumors Cohort 5 Advanced Solid Tumors Cohort 6 Advanced Solid Tumors Cohort 7 Advanced Melanoma Cohort 8 NSCLC Cohort 9 RCC

Name: Cabiralizumab

Description: Cabiralizumab is a humanized Immunoglobulin G (IgG) 4 monoclonal antibody directed against Colony stimulating factor 1 receptor (CSF1R). Cabiralizumab is administered by intravenous infusion.

Type: Drug

Cohort 1 Advanced Solid Tumors Cohort 2 Advanced Solid Tumors Cohort 3 Advanced Solid Tumors Cohort 4 Advanced Solid Tumors Cohort 5 Advanced Solid Tumors Cohort 6 Advanced Solid Tumors Cohort 7 Advanced Melanoma Cohort 8 NSCLC Cohort 9 RCC

Name: Nivolumab

Description: Nivolumab is a humanized IgG4 monoclonal antibody directed against programmed cell death 1 (PD-1). Nivolumab is administered by intravenous infusion.

Type: Drug

Cohort 2 Advanced Solid Tumors Cohort 4 Advanced Solid Tumors Cohort 6 Advanced Solid Tumors Cohort 7 Advanced Melanoma Cohort 9 RCC


Primary Outcomes

Description: AEs and SAEs will be examined with (National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 4.03

Measure: Safety and Tolerability measured by assessing serious adverse events (SAEs)and adverse events (AEs)

Time: From study enrollment up to 12 months.

Description: This 5-point scale ranges from full functioning (1) to dead (5)

Measure: Safety and Tolerability measured by Eastern Cooperative Oncology Group(ECOG) performance status

Time: From study enrollment up to 12 months.

Secondary Outcomes

Description: ORR will be determined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria v. 1.1.

Measure: Efficacy measured by objective response rate (ORR)

Time: Six months.

Other Outcomes

Description: This outcome will be assessed by blood collection.

Measure: Pharmacokinetics (PK) of APX005M assessed by area under the curve (AUC).

Time: 12 weeks

Description: This outcome will be assessed by blood collection.

Measure: Pharmacokinetics (PK) of APX005M assessed by minimum blood plasma concentration (Cmin).

Time: 12 weeks

Description: This outcome will be assessed by blood collection.

Measure: Pharmacokinetics (PK) of APX005M assessed by clearance (CL).

Time: 12 weeks

Description: This outcome will be assessed by blood collection.

Measure: Pharmacokinetics (PK) of APX005M assessed by volume of distribution (Vss)

Time: 12 weeks

Description: This outcome will be assessed by blood collection.

Measure: Pharmacokinetics (PK) of APX005M assessed by peak plasma concentration (Cmax).

Time: 12 weeks

Description: This outcome will be assessed with tissue biopsies.

Measure: Tissue-based pharmacodynamics (PD) of APX005M, in combination with nivolumab and cabiralizumab assessed by CD8+ T cells .

Time: Change from baseline to 8 weeks.

Description: This outcome will be assessed with tissue biopsies.

Measure: Tissue-based pharmacodynamics (PD) of APX005M, in combination with nivolumab and cabiralizumab assessed by CD163+ macrophages .

Time: Change from baseline to 8 weeks.

Description: This outcome will be assessed via blood collection.

Measure: Blood-based pharmacodynamics (PD) of APX005M, in combination with nivolumab and cabiralizumab assessed by circulating CD163+ macrophages .

Time: Change from baseline to 8 weeks.

Description: This outcome will be assessed via blood collection.

Measure: Blood-based pharmacodynamics (PD) of APX005M, in combination with nivolumab and cabiralizumab assessed by circulating CD8+ T cells.

Time: Change from baseline to 8 weeks.

Description: This outcome will be assessed via blood collection.

Measure: Cytokine-based pharmacodynamic (PD) biomarkers of APX005M, in combination with nivolumab and cabiralizumab assessed by CD40L levels.

Time: Change from baseline to 8 weeks.

Description: This outcome will be assessed via blood collection.

Measure: Cytokine-based pharmacodynamic (PD) biomarkers of APX005M, in combination with nivolumab and cabiralizumab assessed by IL-10 levels.

Time: Change from baseline to 8 weeks.

Description: This outcome will be assessed via blood collection.

Measure: Cytokine-based pharmacodynamic (PD) biomarkers of APX005M, in combination with nivolumab and cabiralizumab assessed by interferon-gamma levels .

Time: Change from baseline to 8 weeks.

Description: PFS will be determined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria v. 1.1.

Measure: Efficacy measured by progression-free survival (PFS)

Time: From study enrollment up to 6 years.

Description: OS will be ascertained by review of the National Death Index, medical records and follow-up phone calls.

Measure: Efficacy measured by overall survival (OS)

Time: From study enrollment up to 6 years.

Purpose: Treatment

Allocation: Non-Randomized

Single Group Assignment


There is one SNP

SNPs


1 T790M

Patients with TKI-treated EGFR mutant NSCLC harboring the secondary EGFR T790M tumor must have received prior osimertinib. --- T790M ---



HPO Nodes


HPO:
Carcinoma
Genes 11
PTEN CDKN1B APC MLH1 MSH2 FGFR3 KIT DKC1 RSPO1 STK11 NLRP1
Clear cell renal cell carcinoma
Genes 1
NOD2
Cutaneous melanoma
Genes 11
BRAF HRAS XPC CDKN2A POLH ERCC3 BAP1 CXCR4 MC1R NRAS WRN
Melanoma
Genes 64
RAD51 RAD51C TYR RAD51D CDKN2A KRAS CDKN2B RAF1 CDKN2D MRE11 CYSLTR2 ERCC2 KLLN PTPN11 ERCC3 BRIP1 ERCC4 ERCC5 ERCC6 SF3B1 NRAS MGMT BRCA1 MBTPS2 BRAF ACD BRCA2 PIK3CA CXCR4 CTSC POLH POT1 MC1R MITF WRN CHEK2 HRAS BARD1 NBN AKT1 SLC45A2 GNA11 TRPV3 XPA OCA2 XPC GNAQ PTEN MDM2 TERT DDB2 RNF43 PALLD PALB2 TERF2IP SEC23B TP53 SDHB SDHC SDHD SMAD4 BAP1 CDK4 RAD50
Neoplasm of the lung
Genes 43
WT1 KRAS SLC22A18 STK11 IRF1 AKT1 C11ORF95 PRKN PPP2R1B ERBB2 TRPV3 TSC1 POU6F2 TSC2 EWSR1 RELA KEAP1 REST DIS3L2 SFTPA2 GPC3 MBTPS2 LMNA PTEN BRAF BRCA2 EGFR RB1 TRIP13 PDGFRB TERT SFTPC PIK3CA TRIM28 DICER1 MAP3K8 HPGD SLCO2A1 H19 TP53 NOTCH3 BAP1 WRN
Non-small cell lung carcinoma
Genes 2
TP53 BAP1
Papillary renal cell carcinoma
Genes 8
FOXE1 LMNA HABP2 CDC73 MET MINPP1 PRCC FH
Renal cell carcinoma
Genes 52
FOXE1 VHL MET STK11 HNF1A HNF1B KLLN DLC1 NRAS FN1 LMNA SDHAF2 PIK3CA PRCC MAX KIF1B SRC SLC49A4 BUB1B APC FLCN COL14A1 AKT1 TSC1 TSC2 HABP2 FGFR3 CDC73 KEAP1 MINPP1 CTNNB1 RET DCC FH MDH2 PTEN RNF139 HNF4A AAGAB TMEM127 OGG1 DICER1 EP300 SEC23B SDHA SDHB TFE3 SDHC SDHD AXIN2 BAP1 NOD2