A Study of Amivantamab and Olomorasib Combination Therapy... | NCT07227025

ID	Type	Description	Link
61186372PANSC2004	Other Identifier	Janssen Research & Development, LLC

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Phase 1: Combination Dose Selection	Experimental	Participants will receive amivantamab along with olomorasib to determine the RP2CD of the combination therapy until disease progression, significant toxicity, or until another criterion for discontinuation of study treatment is met. Eligible participants may have the option to transfer to a long-term extension (LTE) phase for continued access to study treatments.	Drug: Amivantamab Drug: Olomorasib
Phase 2: Expansion	Experimental	Participants will receive amivantamab and olomorasib combination therapy at the RP2CD determined in Phase 1 until disease progression, significant toxicity, or until another criterion for discontinuation of study treatment is met. Eligible participants may have the option to transfer to LTE phase for continued access to study treatments.	Drug: Amivantamab Drug: Olomorasib

Name	Type	Description	Arm Group Labels	Other Names
Amivantamab	Drug	Amivantamab will be administered.	Phase 1: Combination Dose Selection Phase 2: Expansion

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Phase 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).	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.	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).	Up to approximately 3 years 2 months

Secondary Outcomes

Measure	Description	Time Frame
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).

Eligibility Module

Eligibility Criteria

Inclusion criteria:

Participant must have histologically or cytologically confirmed metastatic NSCLC characterized by a KRAS G12C mutation at the time of enrollment. For Phase 1: Participant must have progressed on or after, or have intolerance to, platinum-based chemotherapy and Programmed Death-Ligand 1 (PD-L1)-targeted immunotherapy given in combination or sequentially. Receipt of additional lines of prior therapy is permitted. Progression must have occurred on or after the most recent line of systemic anticancer therapy. For Phase 2: Participant must have progressed on or after platinum-based chemotherapy and PD-L1-targeted immunotherapy given in combination or sequentially. Progression must have occurred on or after the most recent line of systemic anticancer therapy. Receipt of additional lines of prior therapy is not permitted
Participant must have at least 1 measurable lesion, according to RECIST version.1.1, that has not been previously irradiated
May have brain metastases only if previously definitively, locally treated, and participant is clinically stable and asymptomatic for greater than (>) 2 weeks and is off or receiving low-dose corticosteroid treatment for at least 2 weeks prior to start of study treatment
Can have a prior or concurrent second malignancy (other than the disease under study) with natural history or treatment course that is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion criteria:

Participant has history of uncontrolled illness
Suspected or known allergies, hypersensitivity, or intolerance to amivantamab excipients or olomorasib excipients
Medical history of (non-infectious) interstitial lung disease (ILD)/pneumonitis, or has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
Presence of primary driver mutations (epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK], mesenchymal-epithelial transition [MET], human epidermal growth factor receptor 2 [HER2], ROS1, neurotrophic tyrosine receptor kinase [NTRK], B-Raf proto-oncogene [BRAF], rearranged during Transfection [RET], neuroblastoma RAS viral oncogene homolog [NRAS], and other KRAS mutations besides G12C) as determined by local genomic testing
Prior treatment with any KRAS inhibitor

Name	Role	Phone	Extension	Email
Study Contact	Contact	844-434-4210		Participate-In-This-Study1@its.jnj.com

Name	Affiliation	Role
Janssen Research & Development, LLC Clinical Trial	Janssen Research & Development, LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of California Irvine	Suspended	Irvine	California	92697	United States

IPD Sharing Statement Module

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases