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]).

A Study of Amivantamab and Olomorasib Combination Therapy in Participants With Metastatic Non-Small Cell Lung Cancer

Carcinoma, Non-Small-Cell Lung

Carcinoma, Non-small-Cell Lung

Carcinoma, Non-Small Cell Lung

Non-Small Cell Lung Cancer

Non-Small-Cell Lung Carcinoma

Lung Cancer

Lung; Node

Cancer of the Lung

Cancer of Lung

Neoplasms, Lung

Lung Neoplasms

Advanced Solid Tumors

Cancer

Advanced Solid Malignancies

Advanced Solid Tumor

Solid Tumor, Adult

Neoplasms

Adenocarcinoma

Advanced Stage Solid Tumors

Amivantamab

Olomorasib

A Phase 1/2 Study Evaluating the Safety and Efficacy of Amivantamab and Olomorasib Combination Therapy in Metastatic Non-small Cell Lung Cancer

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).

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.

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).

Number of participants with abnormalities in clinical laboratory values (which includes serum chemistry, hematology, coagulation, urinalysis, and serology) will be reported.

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.

DCR is defined as the percentage of participants who achieve a PR, CR, or stable disease using RECIST v1.1.

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.

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.

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.

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.

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]).

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).

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.

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).

Number of participants with abnormalities in clinical laboratory values (which includes
serum chemistry, hematology, coagulation, urinalysis, and serology) will be reported.

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.

DCR is defined as the percentage of participants who achieve a PR, CR, or stable disease
using RECIST v1.1.

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.

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.

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.

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.

A Study of Amivantamab and Olomorasib Combination Therapy in Participants With Metastatic Non-Small Cell Lung Cancer

Trials at a glance

Trials at a glance