First-in-Human Study of JNJ-74699157 in Participants With Tumors Harboring the KRAS G12C Mutation
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|ClinicalTrials.gov Identifier: NCT04006301|
Recruitment Status : Recruiting
First Posted : July 3, 2019
Last Update Posted : November 8, 2019
|Condition or disease||Intervention/treatment||Phase|
|Neoplasms Advanced Solid Tumors Non-small Cell Lung Cancer Colorectal Cancer||Drug: JNJ-74699157||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||140 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||July 26, 2019|
|Estimated Primary Completion Date :||July 6, 2023|
|Estimated Study Completion Date :||July 6, 2023|
Experimental: Part 1: Dose Escalation
Participants with advanced solid tumors harboring the kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) mutation will receive oral administration of JNJ-74699157. The dose levels will be escalated sequentially based on the decisions of the Study Evaluation Team (SET) until the recommended Phase 2 Dose (RP2D) has been identified.
Participants will receive JNJ-74699157 orally.
Other Name: ARS-3248
Experimental: Part 2: Dose Expansion
Two groups of participants with either non-small cell lung cancer or other solid tumors harboring KRAS G12C mutation will receive JNJ-74699157 at RP2D determined in Part 1.
Participants will receive JNJ-74699157 orally.
Other Name: ARS-3248
- Part 1: Number of Participants with Dose-Limiting Toxicity (DLT) [ Time Frame: Up to 2 years ]DLTs are defined as certain non-hematologic and hematologic toxicities of Grade 3 or higher.
- Part 1 and Part 2: Number of Participants with Adverse Events (AEs) [ Time Frame: Up to 4 years ]An AE is any untoward medical occurrence in a participant who received study drug without regard to causal relationship.
- Part 1 and Part 2: Number of Participants with AE's by Severity [ Time Frame: Up to 4 years ]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.
- Part 2: Overall Response Rate (ORR) [ Time Frame: Up to 4 years ]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.
- Part 1 and Part 2: Maximum Observed Plasma Concentration (Cmax) of JNJ-74699157 [ Time Frame: Up to 4 years ]Cmax is the maximum observed plasma concentration.
- Part 1 and Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-74699157 [ Time Frame: Up to 4 years ]Tmax is defined as actual sampling time to reach maximum observed plasma concentration.
- Part 1 and 2: Area Under Plasma-concentration Time Curve from Time 0 to Time of Last Quantifiable Concentration (AUC [0-last]) [ Time Frame: Up to 4 years ]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 [ Time Frame: Up to 4 Years ]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 [ Time Frame: Up to 4 years ]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.
- Part 1 and Part 2: Duration of Response (DOR) [ Time Frame: Up to 4 years ]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).
- Change From Baseline in QTc Interval Based on the Fridericia Correction (QTcF) Method [ Time Frame: Baseline up to 4 years ]Change from baseline in QTcF intervals will be assessed.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04006301
|Contact: Study Contact||844-434-4210||JNJ.CT@sylogent.com|
|United States, Florida|
|Florida Cancer Specialists||Recruiting|
|Sarasota, Florida, United States, 34232|
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|Tampa, Florida, United States, 33612|
|United States, New York|
|Memorial Sloan Kettering Cancer Center||Not yet recruiting|
|New York, New York, United States, 10065|
|United States, Tennessee|
|Sarah Cannon Research Institute||Recruiting|
|Nashville, Tennessee, United States, 37203|
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|NEXT Oncology||Not yet recruiting|
|San Antonio, Texas, United States, 78229|
|Centre Leon Bérard||Recruiting|
|Lyon Cedex 8, France, 69373|
|Hopital de la Timone||Recruiting|
|Marseille, France, 13885|
|Institut Gustave Roussy||Recruiting|
|Villejuif, France, 94800|
|Hosp. Univ. Vall D Hebron||Not yet recruiting|
|Barcelona, Spain, 8035|
|Hosp. Univ. Fund. Jimenez Diaz||Not yet recruiting|
|Madrid, Spain, 28040|
|Hosp. Univ. Hm Sanchinarro||Not yet recruiting|
|Madrid, Spain, 28050|
|Hosp. Virgen de La Victoria||Not yet recruiting|
|Málaga, Spain, 29010|
|Study Director:||Janssen Research & Development, LLC Clinical Trial||Janssen Research & Development, LLC|