First-in-Human Study of JNJ-74699157 in Participants With Tumors Harboring the KRAS G12C Mutation

NCT04006301 | Completed Phase 1 FDA Drug

• 3 other identifiers: CR1086522019-000565-2174699157STM1001
• Study Type: interventional
• Target: 10
• Locations: 2 countries
• Sites: 7

Brief Summary

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).

Conditions

Neoplasms; Advanced Solid Tumors; Non-small Cell Lung Cancer; Colorectal Cancer

Keywords

KRAS G12C

Outcome Measures

Primary Outcomes (4)

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

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

  Up to 2 years

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

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

  Up to 4 years

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

  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.

  Up to 4 years

• Part 2: Overall Response Rate (ORR)

  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.

  Up to 4 years

Secondary Outcomes (7)

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

  Up to 4 years

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

  Up to 4 years

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

  Up to 4 years

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

  Up to 4 Years

• Part 1: Overall Response Rate

  Up to 4 years

Study Arms (2)

Part 1: Dose Escalation

EXPERIMENTAL

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.

Drug: JNJ-74699157

Part 2: Dose Expansion

EXPERIMENTAL

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.

Drug: JNJ-74699157

Interventions

JNJ-74699157 DRUG

Participants will receive JNJ-74699157 orally.

Also known as: ARS-3248

Part 1: Dose Escalation; Part 2: Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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. For NSCLC: previously received a platinum-containing chemotherapy regimen and an anti- programmed death-ligand 1 (PD1/PDL1) antibody, unless participant refused or was ineligible to receive such therapy; and for colorectal cancer (CRC): previously received at least 2 prior lines of therapy, including a fluoropyrimidine, oxaliplatin, and irinotecan, unless participant refused or was ineligible to receive such therapy. For Participants in France only: NSCLC: Previously received a platinum-containing chemotherapy regimen and an anti-PD1/PDL1 antibody or was ineligible to receive such therapy. CRC: Previously received at least 2 prior lines of therapy, including a fluoropyrimidine, oxaliplatin, and irinotecan or was ineligible to receive such therapy
• Measurable or evaluable disease: Part 1: either measurable or evaluable disease, Part 2: At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1

You may not qualify if:

• Symptomatic brain metastases or known leptomeningeal disease; asymptomatic brain metastases are allowed if they have been treated, have been stable for greater than or equal to (\>=) 4 weeks as documented by radiographic imaging, and do not require prolonged (greater than \[\>\]14 days) systemic corticosteroid therapy. 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. Exceptions include squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 2 years
• Inability to take an orally administered drug, or medical disorder or prior surgical resection that may affect the absorption of the study drug. Such conditions include, but are not limited to, malabsorption syndrome, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or resection of the stomach or small bowel. If any of these conditions exist, the investigator should discuss with the sponsor to determine participant eligibility

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (7)

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

H. Lee Moffitt Cancer & Research Institute

Tampa, Florida, 33612, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

Centre Leon Bérard

Lyon, 69373, France

Location

Hopital de la Timone

Marseille, 13885, France

Location

Institut Gustave Roussy

Villejuif, 94800, France

Location

Related Publications (1)

• Wang J, Martin-Romano P, Cassier P, Johnson M, Haura E, Lenox L, Guo Y, Bandyopadhyay N, Russell M, Shearin E, Lauring J, Dahan L. Phase I Study of JNJ-74699157 in Patients with Advanced Solid Tumors Harboring the KRAS G12C Mutation. Oncologist. 2022 Jul 5;27(7):536-e553. doi: 10.1093/oncolo/oyab080.

  PMID: 35325211 DERIVED

MeSH Terms

Conditions

Neoplasms; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2019
• First Posted: July 5, 2019
• Study Start: July 26, 2019
• Primary Completion: July 13, 2020
• Study Completion: July 13, 2020
• Last Updated: November 6, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will share

Locations

US (4); FR (3)