The main purpose of this study is to find out the most suitable dose (recommended phase 2 combination dose \[RP2CD\]) of amivantamab and olomorasib combination therapy and to assess how well the combination slows down or prevents the growth of tumors in participants with KRAS G12C mutant metastatic non-small cell lung cancer (NSCLC: the most common type of lung cancer; metastatic: has spread to other parts of the body; KRAS G12C mutant: mutation \[change\] in the kirsten rat sarcoma viral oncogene homolog \[KRAS\] gene in tumor cells in which glycine \[G\] at position 12 is replaced with cystine \[C\]).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Amivantamab will be administered.
Olomorasib will be administered.
New York University Langone Medical Center
New York, New York, United States
RECRUITINGVirginia Cancer Specialists
Fairfax, Virginia, United States
RECRUITINGPrincess Margaret Hospital
Toronto, Ontario, Canada
RECRUITINGShanghai East Hospital
Shanghai, China
RECRUITINGSamsung Medical Center
Seoul, South Korea
RECRUITINGPhase 1: Number of Participants with Adverse Events (AEs) by Severity
An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An assessment of severity grade will be made by the investigator according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 defined as follows: Grade 1 (mild; asymptomatic or mild symptoms; intervention not indicated); Grade 2 (moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living \[ADL\]); Grade 3 (severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL); Grade 4 (life-threatening consequences; urgent intervention indicated); Grade 5 (Death related to adverse event).
Time frame: Up to approximately 3 years 2 months
Phase 1: Number of Participants with Dose-Limiting Toxicities (DLTs)
DLT is defined as drug related adverse events and includes unacceptable non-hematologic toxicity, hematologic toxicity, pulmonary toxicity, or elevations in hepatic enzymes suggestive of drug-induced liver injury of Grade 3 or higher. Toxicities will be graded for severity according to the NCI-CTCAE, version 5.0.
Time frame: Up to approximately 3 years 2 months
Phase 2: Confirmed Objective Response Rate (ORR)
ORR is defined as the percentage of participants who achieve either a confirmed partial response (PR) or complete response (CR), using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 by investigator review. Confirmatory analysis may be performed using Blinded Independent Central Review (BICR).
Time frame: Up to approximately 3 years 2 months
Number of Participants with Adverse Events (AEs) by Severity
An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An assessment of severity grade will be made by the investigator according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 defined as follows: Grade 1 (mild; asymptomatic or mild symptoms; intervention not indicated); Grade 2 (moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living \[ADL\]); Grade 3 (severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL); Grade 4 (life-threatening consequences; urgent intervention indicated); Grade 5 (Death related to adverse event).
Time frame: Up to approximately 3 years 2 months
Number of Participants with Abnormalities in Clinical Laboratory Parameters
Number of participants with abnormalities in clinical laboratory values (which includes serum chemistry, hematology, coagulation, urinalysis, and serology) will be reported.
Time frame: Up to approximately 3 years 2 months
Phase 2: Duration of Response (DoR)
DoR is defined as the time from the date of first documented response (PR or CR) until the date of documented progression or death from any case, whichever comes first, for participant who have PR or CR according to RECIST v1.1 by investigator review.
Time frame: Up to approximately 3 years 2 months
Phase 2: Disease Control Rate (DCR)
DCR is defined as the percentage of participants who achieve a PR, CR, or stable disease using RECIST v1.1.
Time frame: Up to approximately 3 years 2 months
Phase 2: Progression-Free Survival (PFS)
PFS is defined as the time from first dose date until the date of disease progression or death, whichever comes first, based on investigator assessment using RECIST v1.1 by investigator review.
Time frame: Up to approximately 3 years 2 months
Phase 2: Overall Survival (OS)
OS is defined as the time from the date of administration of the first dose of study treatment until the date of death due to any cause.
Time frame: Up to approximately 3 years 2 months
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