SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03228667

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

QUILT-3.055: A Phase IIb, Single-Arm, Multicohort, Open-Label Study of ALT-803 in Combination With PD-1/PD-L1 Checkpoint Inhibitor in Patients Who Have Disease Progression Following an Initial Response to Treatment With PD-1/PD-L1 Checkpoint Inhibitor Therapy

This is a Phase IIb, single-arm, multicohort, open-label multicenter study of ALT-803 in combination with an FDA-approved PD-1/PD-L1 checkpoint inhibitor in patients with advanced cancers who have progressed following an initial response to treatment with PD-1/PD-L1 checkpoint inhibitor therapy. All patients will receive the combination treatment of PD-1/PD-L1 checkpoint inhibitor plus ALT-803 for up to 16 cycles. Each cycle is six weeks in duration. All patients will receive ALT-803 once every 3 weeks. Patients will also receive the same checkpoint inhibitor that they received during their previous therapy. Radiologic evaluation will occur at the end of each treatment cycle. Treatment will continue for up to 2 years, or until the patient experiences confirmed progressive disease or unacceptable toxicity, withdraws consent, or if the Investigator feels it is no longer in the patient's best interest to continue treatment. Patients will be followed for disease progression, post-therapies, and survival through 24 months past administration of the first dose of study drug.

NCT03228667 Non-Small Cell Lung Cancer Small Cell Lung Cancer Urothelial Carcinoma Head and Neck Squamous Cell Carcinoma Merkel Cell Carcinoma Melanoma Renal Cell Carcinoma Gastric Cancer Cervical Cancer Hepatocellular Carcinoma Microsatellite Instability Mismatch Repair Deficiency Colorectal Cancer
MeSH: Carcinoma Lung Neoplasms Carcinoma, Non-Small-Cell Lung Melanoma Colorectal Neoplasms Carcinoma, Squamous Cell Carcinoma, Hepatocellular Stomach Neoplasms Uterine Cervical Neoplasms Carcinoma, Renal Cell Small Cell Lung Carcinoma Carcinoma, Transitional Cell Squamous Cell Carcinoma of Head and Neck Carcinoma, Merkel Cell Microsatellite Instability Brain Neoplasms Neoplastic Syndromes, Hereditary
HPO: Brain neoplasm Carcinoma Cervical polyp Cervix cancer Clear cell renal cell carcinoma Cutaneous melanoma Hepatocellular carcinoma Melanoma Merkel cell skin cancer Neoplasm of the large intestine Neoplasm of the lung Neoplasm of the stomach Non-small cell lung carcinoma Papillary renal cell carcinoma Renal cell carcinoma Small cell lung carcinoma Squamous cell carcinoma

4 Interventions

Name: ALT-803 + Pembrolizumab

Description: Patients will receive 200 mg pembrolizumab as an intravenous infusion over 30 minutes every three weeks. Patients will receive 15 µg/kg ALT-803 administered by subcutaneous injection every three weeks.

Type: Drug

Cohort 1 Cohort 2 Cohort 3 Cohort 4

Name: ALT-803 + Nivolumab

Description: Patients will receive 240 mg nivolumab as an intravenous infusion over 30 minutes every two weeks. Patients will receive 15 µg/kg ALT-803 administered by subcutaneous injection every three weeks.

Type: Drug

Cohort 1 Cohort 4

Name: ALT-803 + Atezolizumab

Description: Patients will receive 1200 mg atezolizumab as an intravenous infusion over 60 minutes every 3 weeks; if the first infusion is tolerated, subsequent infusions may be given over 30 minutes. Patients will receive 15 µg/kg ALT-803 administered by subcutaneous injection every three weeks.

Type: Drug

Cohort 1 Cohort 4

Name: ALT-803 + Avelumab

Description: Patients will receive 10 mg/kg avelumab as an intravenous infusion over 60 minutes every 2 weeks. Patients will receive 15 µg/kg ALT-803 administered by subcutaneous injection every three weeks.

Type: Drug

Cohort 1 Cohort 4


Primary Outcomes

Description: Assess the anti-tumor activity of ALT-803 in combination with a PD-1/PD-L1 checkpoint inhibitor in patients with advanced cancers who have progressed following an initial response to treatment with PD-1/PD-L1 checkpoint inhibitors.

Measure: Objective Response Rate

Time: 24 months

Secondary Outcomes

Description: Assess time from first treatment to death resulting from cancer.

Measure: Disease-specific Survival

Time: 24 months

Description: Assess time from first treatment to death resulting from any cause.

Measure: Overall Survival

Time: 24 months

Description: Assess time to response

Measure: Time to Response

Time: 24 months

Description: Assess duration of response

Measure: Duration of Response

Time: 24 months

Description: Assess incidence of adverse events.

Measure: Incidence of Adverse Events

Time: 24 months

Description: Compare changes in QOL scores from baseline.

Measure: Quality of Life (QOL)

Time: 24 months

Description: Assess amount of time disease does not get worse after first treatment.

Measure: Progression-free Survival

Time: 24 months

Purpose: Treatment

Allocation: Non-Randomized

Parallel Assignment


There is one SNP

SNPs


1 V600E

Patients with BRAF V600E mutation-positive melanoma were not required to have received prior BRAF inhibitor therapy; OR unresectable or metastatic melanoma with progression, refractory to ≥ 2 doses of ipilimumab (3 mg/kg or higher) and, if BRAF V600 mutation-positive, a BRAF or MEK inhibitor, and disease progression within 24 weeks following the last dose of ipilimumab. --- V600E ---



HPO Nodes


HPO:
Brain neoplasm
Genes 7
POLD1 POLE RELA APC RB1 FLI1 C11ORF95
Carcinoma
Genes 11
PTEN CDKN1B APC MLH1 MSH2 FGFR3 KIT DKC1 RSPO1 STK11 NLRP1
Cervical polyp
Cervix cancer
Genes 4
SRY CDKN1B STK11 CXCR4
Clear cell renal cell carcinoma
Genes 1
NOD2
Cutaneous melanoma
Genes 11
BRAF HRAS XPC CDKN2A POLH ERCC3 BAP1 CXCR4 MC1R NRAS WRN
Hepatocellular carcinoma
Genes 54
PMS1 HFE KRAS MST1 FAH IL12A TGFBR2 MET IL12RB1 MSH6 RASGRP1 TCF4 BMPR1A SERPINA1 PMS2 MLH3 IGF2 IGF2R MMEL1 ATP7B SPIB PDGFRL PIK3CA GPR35 SLC25A13 JAG1 AHCY APC MLH1 TJP2 ABCB11 CASP8 HMBS POU2AF1 CASP10 PRKCD IRF5 RPS20 MSH2 SEMA4A CTNNB1 SPRTN UROD FAS FASLG EPCAM G6PC TNFSF15 SLC37A4 TNPO3 H19 TP53 AXIN1 FAN1
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
Merkel cell skin cancer
Neoplasm of the large intestine
Genes 71
FOXE1 PMS1 CDKN2A KRAS MST1 TGFBR2 STK11 MSH6 TCF4 BMPR1A PMS2 KLLN MLH3 DLC1 NRAS BRCA1 BRCA2 PDGFRA DOCK8 PIK3CA GPR35 POLD1 NTHL1 POLE SRC BUB1 SH3KBP1 BUB1B CHEK2 APC MLH1 PRKAR1A FLCN COL14A1 AKT1 RPS19 RPS20 HABP2 MSH2 FGFR3 MSH3 KEAP1 GREM1 MINPP1 SEMA4A CTNNB1 DCC BUB3 PTEN MDM2 CEP57 ENG AAGAB TRIP13 KIT EPCAM DICER1 RNF43 PALLD EP300 PALB2 SEC23B MUTYH SDHA TP53 SDHB SDHC SDHD AXIN2 SMAD4 FAN1
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
Neoplasm of the stomach
Genes 59
CDKN2A KRAS CDKN2B CDKN2D STK11 MSH6 TREX1 ERBB2 BMPR1A DLC1 NRAS MGMT ACD KLF6 PDGFRA PIK3CA POT1 SRC BUB1 BUB1B MC1R MITF CHEK2 PTCH2 APC MLH1 PRKAR1A FLCN CASP10 IRF1 AKT1 RPS20 BCL10 MSH2 FGFR3 MSH3 FGFR2 SEMA4A CTNNB1 DCC PTCH1 BUB3 SUFU CEP57 ENG CDH1 TRIP13 KIT TERT EP300 TERF2IP MUTYH SDHA SDHB SDHC AXIN2 SMAD4 BAP1 CDK4
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
Small cell lung carcinoma
Squamous cell carcinoma
Genes 62
BLM TYR CDKN2A NUTM1 TGFBR2 KRT5 COL7A1 GTF2E2 GJB2 ERCC2 KRT14 ERCC3 CIB1 ERCC4 ERCC5 WWOX LMNA SASH1 RNF6 TINF2 ING1 SLC17A9 DOCK8 LZTS1 PSENEN FDPS NTHL1 CTSC GJB6 BRD4 POLH RECQL4 RNF113A TMC6 FERMT1 MC1R WRN TMC8 LAMA3 MPLKIP GTF2H5 WNT10A DKC1 LAMB3 NLRP1 LAMC2 SLC45A2 OCA2 XPC MMP1 TNFRSF10B DCC WRAP53 TERC TERT RSPO1 DDB2 SLX4 STAT1 MVD IL7 MVK