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).
Name: JNJ-74699157
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 yearsDescription: 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 yearsDescription: 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 yearsDescription: 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 yearsDescription: 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 yearsDescription: 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 yearsDescription: 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 yearsDescription: 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 YearsDescription: 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 yearsDescription: 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 yearsDescription: 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 yearsAllocation: Non-Randomized
Sequential Assignment
There is one SNP
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 ---