SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT04006301

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A First-in-Human Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of JNJ-74699157 in Participants With Advanced Solid Tumors Harboring the KRAS G12C Mutation

The purpose of this study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of JNJ-74699157 in participants with advanced solid tumors harboring a kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) mutation (Part 1: Dose escalation) and to determine the safety and preliminary antitumor activity of JNJ-74699157 at the RP2D regimen in participants with advanced solid tumors harboring a KRAS G12C mutation (Part 2: Dose expansion).

NCT04006301 Neoplasms Advanced Solid Tumors Non-small Cell Lung Cancer Colorectal Cancer
MeSH: Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms
HPO: Neoplasm of the large intestine Non-small cell lung carcinoma

1 Interventions

Name: JNJ-74699157

Description: Participants will receive JNJ-74699157 orally.

Type: Drug

Part 1: Dose Escalation Part 2: Dose Expansion


Primary Outcomes

Description: DLTs are defined as certain non-hematologic and hematologic toxicities of Grade 3 or higher.

Measure: Part 1: Number of Participants with Dose-Limiting Toxicity (DLT)

Time: Up to 2 years

Description: An AE is any untoward medical occurrence in a participant who received study drug without regard to causal relationship.

Measure: Part 1 and Part 2: Number of Participants with Adverse Events (AEs)

Time: Up to 4 years

Description: Severity of AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life threatening consequences; Grade 5: Death.

Measure: Part 1 and Part 2: Number of Participants with AE's by Severity

Time: Up to 4 years

Description: ORR is defined as the percentage of participants who have a partial response (PR) or better response as per RECIST v.1.1. PR criteria in solid tumors (RECIST) is greater than or equal to (>=) 30 percent (%) decrease in the sum of the diameters of all index lesions compared with baseline in 2 observations at least 4 weeks apart, in absence of new lesions or unequivocal progression of non-index lesions.

Measure: Part 2: Overall Response Rate (ORR)

Time: Up to 4 years

Secondary Outcomes

Description: Cmax is the maximum observed plasma concentration.

Measure: Part 1 and Part 2: Maximum Observed Plasma Concentration (Cmax) of JNJ-74699157

Time: Up to 4 years

Description: Tmax is defined as actual sampling time to reach maximum observed plasma concentration.

Measure: Part 1 and Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-74699157

Time: Up to 4 years

Description: AUC (0-last) is the area under the plasma concentration-time curve from time zero to last observed quantifiable concentration.

Measure: Part 1 and 2: Area Under Plasma-concentration Time Curve from Time 0 to Time of Last Quantifiable Concentration (AUC [0-last])

Time: Up to 4 years

Description: Percentage of kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) protein in tumor tissue covalently bound with JNJ-74699157 or its metabolites will be evaluated using mass spectroscopy.

Measure: Part 1 and 2: Percentage of KRAS G12C Protein in Tumor Tissue Covalently Bound with JNJ-74699157 or its Metabolites

Time: Up to 4 Years

Description: ORR is defined as the percentage of participants who have a PR or better response as per RECIST v.1.1. PR criteria in solid tumors (RECIST) is >=30 percent % decrease in the sum of the diameters of all index lesions compared with baseline in 2 observations at least 4 weeks apart, in absence of new lesions or unequivocal progression of non-index lesions.

Measure: Part 1: Overall Response Rate

Time: Up to 4 years

Description: DOR is defined as the duration from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease (PD), as defined in the RECIST v1.1, or death due to any cause, whichever occurs first. PD is assessed if the sum of the diameters has increased by >=20% and >=5 millimeter (mm) from nadir (including baseline if it is the smallest sum).

Measure: Part 1 and Part 2: Duration of Response (DOR)

Time: Up to 4 years

Description: Change from baseline in QTcF intervals will be assessed.

Measure: Change From Baseline in QTc Interval Based on the Fridericia Correction (QTcF) Method

Time: Baseline up to 4 years

Purpose: Treatment

Allocation: Non-Randomized

Sequential Assignment


There is one SNP

SNPs


1 G12C

A First-in-Human Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of JNJ-74699157 in Participants With Advanced Solid Tumors Harboring the KRAS G12C Mutation. --- G12C ---

First-in-Human Study of JNJ-74699157 in Participants With Tumors Harboring the KRAS G12C Mutation The purpose of this study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of JNJ-74699157 in participants with advanced solid tumors harboring a kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) mutation (Part 1: Dose escalation) and to determine the safety and preliminary antitumor activity of JNJ-74699157 at the RP2D regimen in participants with advanced solid tumors harboring a KRAS G12C mutation (Part 2: Dose expansion). --- G12C ---

First-in-Human Study of JNJ-74699157 in Participants With Tumors Harboring the KRAS G12C Mutation The purpose of this study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of JNJ-74699157 in participants with advanced solid tumors harboring a kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) mutation (Part 1: Dose escalation) and to determine the safety and preliminary antitumor activity of JNJ-74699157 at the RP2D regimen in participants with advanced solid tumors harboring a KRAS G12C mutation (Part 2: Dose expansion). --- G12C --- --- G12C ---

First-in-Human Study of JNJ-74699157 in Participants With Tumors Harboring the KRAS G12C Mutation The purpose of this study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of JNJ-74699157 in participants with advanced solid tumors harboring a kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) mutation (Part 1: Dose escalation) and to determine the safety and preliminary antitumor activity of JNJ-74699157 at the RP2D regimen in participants with advanced solid tumors harboring a KRAS G12C mutation (Part 2: Dose expansion). --- G12C --- --- G12C --- --- G12C ---

AUC (0-last) is the area under the plasma concentration-time curve from time zero to last observed quantifiable concentration.. Part 1 and 2: Percentage of KRAS G12C Protein in Tumor Tissue Covalently Bound with JNJ-74699157 or its Metabolites. --- G12C ---

Percentage of kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) protein in tumor tissue covalently bound with JNJ-74699157 or its metabolites will be evaluated using mass spectroscopy.. Part 1: Overall Response Rate. --- G12C ---

Change from baseline in QTcF intervals will be assessed.. Inclusion Criteria: - Kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) mutation in tumor tissue or blood - Histological documentation of disease: Part 1: Histologically or cytologically confirmed solid tumor malignancy that is metastatic or unresectable, Part 2: (a) unresectable, locally advanced (Stage IIIB) or metastatic (Stage IV) non-small cell lung cancer (NSCLC), (b) Solid tumor malignancy other than NSCLC that is metastatic or unresectable - Received or was ineligible for standard treatment options. --- G12C ---

Participants who have had complete surgical resection of or received stereotactic radiosurgery to less than or equal to (<=) 3 metastatic lesions will be permitted to enroll in the study within 14 days of such treatment if they have recovered from treatment, are clinically stable, and do not require prolonged systemic corticosteroid therapy as noted above - Prior treatment with an inhibitor specific to KRAS G12C - Prior solid organ transplantation - History of malignancy (other than the disease under study) within 2 years before the first administration of study drug. --- G12C ---

If any of these conditions exist, the investigator should discuss with the sponsor to determine participant eligibility Inclusion Criteria: - Kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) mutation in tumor tissue or blood - Histological documentation of disease: Part 1: Histologically or cytologically confirmed solid tumor malignancy that is metastatic or unresectable, Part 2: (a) unresectable, locally advanced (Stage IIIB) or metastatic (Stage IV) non-small cell lung cancer (NSCLC), (b) Solid tumor malignancy other than NSCLC that is metastatic or unresectable - Received or was ineligible for standard treatment options. --- G12C ---

This study will evaluate JNJ-74699157, a potent and specific, orally bioavailable inhibitor of the glycine-to-cysteine (G12C) mutant KRAS protein, which is found in non-small cell lung cancers and other solid tumor types. --- G12C ---

This study will enroll participants with advanced solid tumors harboring the KRAS G12C mutation and will be conducted in 2 parts. --- G12C ---



HPO Nodes


HPO:
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
Non-small cell lung carcinoma
Genes 2
TP53 BAP1