Combination Study of RMC-4630 and Sotorasib for NSCLC Sub... | NCT05054725

Name	Class
Sanofi	INDUSTRY
Amgen	INDUSTRY

Label	Type	Description	Intervention Names
RMC-4630 and sotorasib, Safety Run-in	Experimental	Safety Run-In: RMC-4630 and sotorasib	Drug: RMC-4630 Drug: Sotorasib
RMC-4630 and sotorasib, Expansion	Experimental	Dose Expansion: RMC-4630 and sotorasib	Drug: RMC-4630 Drug: Sotorasib

Name	Type	Description	Arm Group Labels	Other Names
RMC-4630	Drug	RMC-4630 administered orally as a capsule	RMC-4630 and sotorasib, Expansion RMC-4630 and sotorasib, Safety Run-in

Measure	Description	Time Frame
Objective Response Rate (ORR) as Assessed Per RECIST v1.1	Evaluation of the antitumor effects of RMC-4630 and sotorasib in locally advanced or metastatic NSCLC patients with KRASG12C mutation with and without co-existing genetic aberrations in specific genes such as STK11/LKB1, KEAP1, and PIK3CA after failure of prior standard therapy. Objective Response Rate (%) is defined as the proportion of patients with Best Overall Response of confirmed CR, or PR. Response was confirmed by a repeat assessment no less than 28 days.	31 months

Measure	Description	Time Frame
Clinically Significant Changes in Vital Signs	Characterization of the safety, tolerability of RMC-4630 in combination with sotorasib for subjects with KRASG12C mutant NSCLC after failure of prior standard therapy	31 months
Clinically Significant Changes in Laboratory Tests

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subject must be ≥18 years of age.
Subject must have pathologically documented, locally advanced or metastatic KRASG12C NSCLC (not amenable to curative surgery) that has progressed on prior standard therapies (no more than 3 prior lines of therapies are allowed)

Exclusion Criteria

Primary central nervous system (CNS) tumors
Known or suspected leptomeningeal or brain metastases or spinal cord compression
Clinically significant cardiac disease
Known impairment of GI function that would alter the absorption
Active autoimmune disease requiring systemic treatment within past 2 years
History of severe allergic reactions to any of the study intervention components
Major surgical procedures within 28 days or non-study-related minor procedures within 7 days of treatment.
Prior therapy with KRASG12C inhibitor and/or SHP2 inhibitor

Name	Affiliation	Role
Revolution Medicines, Inc.	Revolution Medicines, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Florida Cancer Specialists		Fort Myers	Florida	33901	United States
BRCR Medical Center Inc.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD	The two arms have been broken down per dose level rather than by phase or cohort per the CSR, which is provided to FDA and not uploaded to ct.gov. Participants were administered 140 or 200 mg of RMC-4630 twice weekly (BIW) on D1D2 of each week in a 21-day cycle and Sotorasib 960 mg once daily (QD) in a 21-day cycle. The 140mg and 200mg dose levels were explored at the safety run-in stage, and after completion of the safety run-in (DLT clearance) of both dose levels, additional patients were enrolled at both dose levels for the purpose of dose optimization before selecting the final expansion dose. Therefore, both the 140mg and 200mg dose levels included patients in the safety-run in and dose optimization. After that, 200mg was identified as the RP2D dose, which moved to the expansion phase. Statistical analysis for all sections in the results was performed for all treated patients by dose level, i.e., 140mg vs 200mg. For patients enrolled at the RP2D dose level of 200mg, analysis was further performed based on mutation status, i.e., cohorts 1 vs 2.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Sep 6, 2023	Jun 27, 2025

Arm/Group Information

ID	Title	Description
BG000	RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD	The two arms have been broken down per dose level rather than by phase or cohort per the CSR, which is provided to FDA and not uploaded to ct.gov. Participants were administered 140 or 200 mg of RMC-4630 twice weekly (BIW) on D1D2 of each week in a 21-day cycle and Sotorasib 960 mg once daily (QD) in a 21-day cycle. The 140mg and 200mg dose levels were explored at the safety run-in stage, and after completion of the safety run-in (DLT clearance) of both dose levels, additional patients were enrolled at both dose levels for the purpose of dose optimization before selecting the final expansion dose. Therefore, both the 140mg and 200mg dose levels included patients in the safety-run in and dose optimization. After that, 200mg was identified as the RP2D dose, which moved to the expansion phase. Statistical analysis for all sections in the results was performed for all treated patients by dose level, i.e., 140mg vs 200mg. For patients enrolled at the RP2D dose level of 200mg, analysis was further performed based on mutation status, i.e., cohorts 1 vs 2.
BG001	RMC-4630 200 mg D1D2 + Sotorasib 960 mg QD	The two arms have been broken down per dose level rather than by phase or cohort per the CSR, which is provided to FDA and not uploaded to ct.gov. Participants were administered 140 or 200 mg of RMC-4630 twice weekly (BIW) on D1D2 of each week in a 21-day cycle and Sotorasib 960 mg once daily (QD) in a 21-day cycle. The 140mg and 200mg dose levels were explored at the safety run-in stage, and after completion of the safety run-in (DLT clearance) of both dose levels, additional patients were enrolled at both dose levels for the purpose of dose optimization before selecting the final expansion dose. Therefore, both the 140mg and 200mg dose levels included patients in the safety-run in and dose optimization. After that, 200mg was identified as the RP2D dose, which moved to the expansion phase. Statistical analysis for all sections in the results was performed for all treated patients by dose level, i.e., 140mg vs 200mg. For patients enrolled at the RP2D dose level of 200mg, analysis was further performed based on mutation status, i.e., cohorts 1 vs 2.
BG002	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Objective Response Rate (ORR) as Assessed Per RECIST v1.1

Evaluation of the antitumor effects of RMC-4630 and sotorasib in locally advanced or metastatic NSCLC patients with KRASG12C mutation with and without co-existing genetic aberrations in specific genes such as STK11/LKB1, KEAP1, and PIK3CA after failure of prior standard therapy. Objective Response Rate (%) is defined as the proportion of patients with Best Overall Response of confirmed CR, or PR. Response was confirmed by a repeat assessment no less than 28 days.

Objective Response Rate (%) is defined as the proportion of patients with Best Overall Response of confirmed CR, or PR.

Posted

Count of Participants

Participants

31 months

ID	Title	Description
OG000	RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD	The two arms have been broken down per dose level rather than by phase or cohort per the CSR, which is provided to FDA and not uploaded to ct.gov. Participants were administered 140 or 200 mg of RMC-4630 twice weekly (BIW) on D1D2 of each week in a 21-day cycle and Sotorasib 960 mg once daily (QD) in a 21-day cycle. The 140mg and 200mg dose levels were explored at the safety run-in stage, and after completion of the safety run-in (DLT clearance) of both dose levels, additional patients were enrolled at both dose levels for the purpose of dose optimization before selecting the final expansion dose. Therefore, both the 140mg and 200mg dose levels included patients in the safety-run in and dose optimization. After that, 200mg was identified as the RP2D dose, which moved to the expansion phase. Statistical analysis for all sections in the results was performed for all treated patients by dose level, i.e., 140mg vs 200mg. For patients enrolled at the RP2D dose level of 200mg, analysis was further performed based on mutation status, i.e., cohorts 1 vs 2.
OG001	RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD	The two arms have been broken down per dose level rather than by phase or cohort per the CSR, which is provided to FDA and not uploaded to ct.gov. Participants were administered 140 or 200 mg of RMC-4630 twice weekly (BIW) on D1D2 of each week in a 21-day cycle and Sotorasib 960 mg once daily (QD) in a 21-day cycle. The 140mg and 200mg dose levels were explored at the safety run-in stage, and after completion of the safety run-in (DLT clearance) of both dose levels, additional patients were enrolled at both dose levels for the purpose of dose optimization before selecting the final expansion dose. Therefore, both the 140mg and 200mg dose levels included patients in the safety-run in and dose optimization. After that, 200mg was identified as the RP2D dose, which moved to the expansion phase. Statistical analysis for all sections in the results was performed for all treated patients by dose level, i.e., 140mg vs 200mg. For patients enrolled at the RP2D dose level of 200mg, analysis was further performed based on mutation status, i.e., cohorts 1 vs 2.

Units	Counts
Participants	OG0004 OG00143

Title

Denominators

Categories

Title	Measurements
	OG0000 OG00111

Secondary

Clinically Significant Changes in Vital Signs

Characterization of the safety, tolerability of RMC-4630 in combination with sotorasib for subjects with KRASG12C mutant NSCLC after failure of prior standard therapy

Posted

Count of Participants

Participants

31 months

ID	Title	Description
OG000	RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD	The two arms have been broken down per dose level rather than by phase or cohort per the CSR, which is provided to FDA and not uploaded to ct.gov. Participants were administered 140 or 200 mg of RMC-4630 twice weekly (BIW) on D1D2 of each week in a 21-day cycle and Sotorasib 960 mg once daily (QD) in a 21-day cycle. The 140mg and 200mg dose levels were explored at the safety run-in stage, and after completion of the safety run-in (DLT clearance) of both dose levels, additional patients were enrolled at both dose levels for the purpose of dose optimization before selecting the final expansion dose. Therefore, both the 140mg and 200mg dose levels included patients in the safety-run in and dose optimization. After that, 200mg was identified as the RP2D dose, which moved to the expansion phase. Statistical analysis for all sections in the results was performed for all treated patients by dose level, i.e., 140mg vs 200mg. For patients enrolled at the RP2D dose level of 200mg, analysis was further performed based on mutation status, i.e., cohorts 1 vs 2.
OG001	RMC-4630 200 mg BIW D1D2 and Sotorasib 960 mg QD Safety-Run in, Optimization, Expansion	The two arms have been broken down per dose level rather than by phase or cohort per the CSR, which is provided to FDA and not uploaded to ct.gov. Participants were administered 140 or 200 mg of RMC-4630 twice weekly (BIW) on D1D2 of each week in a 21-day cycle and Sotorasib 960 mg once daily (QD) in a 21-day cycle. The 140mg and 200mg dose levels were explored at the safety run-in stage, and after completion of the safety run-in (DLT clearance) of both dose levels, additional patients were enrolled at both dose levels for the purpose of dose optimization before selecting the final expansion dose. Therefore, both the 140mg and 200mg dose levels included patients in the safety-run in and dose optimization. After that, 200mg was identified as the RP2D dose, which moved to the expansion phase. Statistical analysis for all sections in the results was performed for all treated patients by dose level, i.e., 140mg vs 200mg. For patients enrolled at the RP2D dose level of 200mg, analysis was further performed based on mutation status, i.e., cohorts 1 vs 2.

Secondary

Clinically Significant Changes in Laboratory Tests

Characterization of the safety, tolerability of RMC-4630 in combination with sotorasib for subjects with KRASG12C mutant NSCLC after failure of prior standard therapy

Posted

Count of Participants

Participants

31 months

ID	Title	Description
OG000	RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD	The two arms have been broken down per dose level rather than by phase or cohort per the CSR, which is provided to FDA and not uploaded to ct.gov. Participants were administered 140 or 200 mg of RMC-4630 twice weekly (BIW) on D1D2 of each week in a 21-day cycle and Sotorasib 960 mg once daily (QD) in a 21-day cycle. The 140mg and 200mg dose levels were explored at the safety run-in stage, and after completion of the safety run-in (DLT clearance) of both dose levels, additional patients were enrolled at both dose levels for the purpose of dose optimization before selecting the final expansion dose. Therefore, both the 140mg and 200mg dose levels included patients in the safety-run in and dose optimization. After that, 200mg was identified as the RP2D dose, which moved to the expansion phase. Statistical analysis for all sections in the results was performed for all treated patients by dose level, i.e., 140mg vs 200mg. For patients enrolled at the RP2D dose level of 200mg, analysis was further performed based on mutation status, i.e., cohorts 1 vs 2.
OG001	RMC-4630 200 mg D1D2 + Sotorasib 960 mg QD	The two arms have been broken down per dose level rather than by phase or cohort per the CSR, which is provided to FDA and not uploaded to ct.gov. Participants were administered 140 or 200 mg of RMC-4630 twice weekly (BIW) on D1D2 of each week in a 21-day cycle and Sotorasib 960 mg once daily (QD) in a 21-day cycle. The 140mg and 200mg dose levels were explored at the safety run-in stage, and after completion of the safety run-in (DLT clearance) of both dose levels, additional patients were enrolled at both dose levels for the purpose of dose optimization before selecting the final expansion dose. Therefore, both the 140mg and 200mg dose levels included patients in the safety-run in and dose optimization. After that, 200mg was identified as the RP2D dose, which moved to the expansion phase. Statistical analysis for all sections in the results was performed for all treated patients by dose level, i.e., 140mg vs 200mg. For patients enrolled at the RP2D dose level of 200mg, analysis was further performed based on mutation status, i.e., cohorts 1 vs 2.

Secondary

Clinically Significant Changes in ECGs

Characterization of the safety, tolerability of RMC-4630 in combination with sotorasib for subjects with KRASG12C mutant NSCLC after failure of prior standard therapy

Posted

Count of Participants

Participants

31 months

ID	Title	Description
OG000	RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD	The two arms have been broken down per dose level rather than by phase or cohort per the CSR, which is provided to FDA and not uploaded to ct.gov. Participants were administered 140 or 200 mg of RMC-4630 twice weekly (BIW) on D1D2 of each week in a 21-day cycle and Sotorasib 960 mg once daily (QD) in a 21-day cycle. The 140mg and 200mg dose levels were explored at the safety run-in stage, and after completion of the safety run-in (DLT clearance) of both dose levels, additional patients were enrolled at both dose levels for the purpose of dose optimization before selecting the final expansion dose. Therefore, both the 140mg and 200mg dose levels included patients in the safety-run in and dose optimization. After that, 200mg was identified as the RP2D dose, which moved to the expansion phase. Statistical analysis for all sections in the results was performed for all treated patients by dose level, i.e., 140mg vs 200mg. For patients enrolled at the RP2D dose level of 200mg, analysis was further performed based on mutation status, i.e., cohorts 1 vs 2.
OG001	RMC-4630 200 mg D1D2 + Sotorasib 960 mg QD	The two arms have been broken down per dose level rather than by phase or cohort per the CSR, which is provided to FDA and not uploaded to ct.gov. Participants were administered 140 or 200 mg of RMC-4630 twice weekly (BIW) on D1D2 of each week in a 21-day cycle and Sotorasib 960 mg once daily (QD) in a 21-day cycle. The 140mg and 200mg dose levels were explored at the safety run-in stage, and after completion of the safety run-in (DLT clearance) of both dose levels, additional patients were enrolled at both dose levels for the purpose of dose optimization before selecting the final expansion dose. Therefore, both the 140mg and 200mg dose levels included patients in the safety-run in and dose optimization. After that, 200mg was identified as the RP2D dose, which moved to the expansion phase. Statistical analysis for all sections in the results was performed for all treated patients by dose level, i.e., 140mg vs 200mg. For patients enrolled at the RP2D dose level of 200mg, analysis was further performed based on mutation status, i.e., cohorts 1 vs 2.

Secondary

Trough and Approximate Peak Concentrations of RMC-4630

Characterization of PK of RMC-4630 in combination with sotorasib for subjects with KRASG12C mutant NSCLC.

Summary of PK of RMC-4630 concentration for subjects with KRASG12C mutant NSCLC (All Treated Subjects). Timepoints beyond Cycle 4 do not any value for the PK profile per sponsor. The decreasing number in participants analyzed is due to various factors such as missed samples or patient drop out as timepoints progressed.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/ml

31 months

ID	Title	Description
OG000	RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD	The two arms have been broken down per dose level rather than by phase or cohort per the CSR, which is provided to FDA and not uploaded to ct.gov. Participants were administered 140 or 200 mg of RMC-4630 twice weekly (BIW) on D1D2 of each week in a 21-day cycle and Sotorasib 960 mg once daily (QD) in a 21-day cycle. The 140mg and 200mg dose levels were explored at the safety run-in stage, and after completion of the safety run-in (DLT clearance) of both dose levels, additional patients were enrolled at both dose levels for the purpose of dose optimization before selecting the final expansion dose. Therefore, both the 140mg and 200mg dose levels included patients in the safety-run in and dose optimization. After that, 200mg was identified as the RP2D dose, which moved to the expansion phase. Statistical analysis for all sections in the results was performed for all treated patients by dose level, i.e., 140mg vs 200mg. For patients enrolled at the RP2D dose level of 200mg, analysis was further performed based on mutation status, i.e., cohorts 1 vs 2.

Secondary

Trough and Approximate Peak Concentrations of Sotorasib

Characterization of PK of RMC-4630 in combination with Sotorasib for subjects with KRASG12C mutant NSCLC

Summary of PK of Sotorasib concentration for subjects with KRASG12C mutant NSCLC (All Treated Subjects). Timepoints beyond Cycle 4 do not any value for the PK profile per sponsor. The decreasing number in participants analyzed is due to various factors such as missed samples or patient drop out as timepoints progressed.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

31 months

ID	Title	Description
OG000	RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD	The two arms have been broken down per dose level rather than by phase or cohort per the CSR, which is provided to FDA and not uploaded to ct.gov. Participants were administered 140 or 200 mg of RMC-4630 twice weekly (BIW) on D1D2 of each week in a 21-day cycle and Sotorasib 960 mg once daily (QD) in a 21-day cycle. The 140mg and 200mg dose levels were explored at the safety run-in stage, and after completion of the safety run-in (DLT clearance) of both dose levels, additional patients were enrolled at both dose levels for the purpose of dose optimization before selecting the final expansion dose. Therefore, both the 140mg and 200mg dose levels included patients in the safety-run in and dose optimization. After that, 200mg was identified as the RP2D dose, which moved to the expansion phase. Statistical analysis for all sections in the results was performed for all treated patients by dose level, i.e., 140mg vs 200mg. For patients enrolled at the RP2D dose level of 200mg, analysis was further performed based on mutation status, i.e., cohorts 1 vs 2.

Secondary

Duration of Response (DOR) as Assessed Per RECIST v1.1

Characterization of efficacy or RMC-4630 in combination with Sotorasib as assessed by DOR, DCR, PFS, and OS in patients with KRAS G12C-mutant locally advanced or metastatic NSCLC after failure of prior standard therapy

Duration of Response (DOR) Based on Investigator Assessments (Subjects with Confirmed CR or PR Responders only).

Posted

Median

95% Confidence Interval

months

31 months

ID	Title	Description
OG000	RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD	The two arms have been broken down per dose level rather than by phase or cohort per the CSR, which is provided to FDA and not uploaded to ct.gov. Participants were administered 140 or 200 mg of RMC-4630 twice weekly (BIW) on D1D2 of each week in a 21-day cycle and Sotorasib 960 mg once daily (QD) in a 21-day cycle. The 140mg and 200mg dose levels were explored at the safety run-in stage, and after completion of the safety run-in (DLT clearance) of both dose levels, additional patients were enrolled at both dose levels for the purpose of dose optimization before selecting the final expansion dose. Therefore, both the 140mg and 200mg dose levels included patients in the safety-run in and dose optimization. After that, 200mg was identified as the RP2D dose, which moved to the expansion phase. Statistical analysis for all sections in the results was performed for all treated patients by dose level, i.e., 140mg vs 200mg. For patients enrolled at the RP2D dose level of 200mg, analysis was further performed based on mutation status, i.e., cohorts 1 vs 2.
OG001

Secondary

Disease Control Rate (DCR) as Assessed Per RECIST v.1.1

Disease Control Rate (%) is defined as the proportion of subjects with best overall response of CR, PR, or stable disease

Posted

Count of Participants

Participants

31 months

ID	Title	Description
OG000	RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD	The two arms have been broken down per dose level rather than by phase or cohort per the CSR, which is provided to FDA and not uploaded to ct.gov. Participants were administered 140 or 200 mg of RMC-4630 twice weekly (BIW) on D1D2 of each week in a 21-day cycle and Sotorasib 960 mg once daily (QD) in a 21-day cycle. The 140mg and 200mg dose levels were explored at the safety run-in stage, and after completion of the safety run-in (DLT clearance) of both dose levels, additional patients were enrolled at both dose levels for the purpose of dose optimization before selecting the final expansion dose. Therefore, both the 140mg and 200mg dose levels included patients in the safety-run in and dose optimization. After that, 200mg was identified as the RP2D dose, which moved to the expansion phase. Statistical analysis for all sections in the results was performed for all treated patients by dose level, i.e., 140mg vs 200mg. For patients enrolled at the RP2D dose level of 200mg, analysis was further performed based on mutation status, i.e., cohorts 1 vs 2.
OG001

Secondary

Progression-free Survival (PFS) as Assessed Per RECIST v1.1

Summary of Progression-Free Survival (PFS) Based on Investigator Assessments (All Treated Subjects).

Posted

Median

95% Confidence Interval

months

31 months

ID	Title	Description
OG000	RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD	The two arms have been broken down per dose level rather than by phase or cohort per the CSR, which is provided to FDA and not uploaded to ct.gov. Participants were administered 140 or 200 mg of RMC-4630 twice weekly (BIW) on D1D2 of each week in a 21-day cycle and Sotorasib 960 mg once daily (QD) in a 21-day cycle. The 140mg and 200mg dose levels were explored at the safety run-in stage, and after completion of the safety run-in (DLT clearance) of both dose levels, additional patients were enrolled at both dose levels for the purpose of dose optimization before selecting the final expansion dose. Therefore, both the 140mg and 200mg dose levels included patients in the safety-run in and dose optimization. After that, 200mg was identified as the RP2D dose, which moved to the expansion phase. Statistical analysis for all sections in the results was performed for all treated patients by dose level, i.e., 140mg vs 200mg. For patients enrolled at the RP2D dose level of 200mg, analysis was further performed based on mutation status, i.e., cohorts 1 vs 2.
OG001

Secondary

Overall Survival (OS)

Summary of Overall Survival (OS) (All Treated Subjects).

Posted

Median

95% Confidence Interval

months

31 months

ID	Title	Description
OG000	RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD	The two arms have been broken down per dose level rather than by phase or cohort per the CSR, which is provided to FDA and not uploaded to ct.gov. Participants were administered 140 or 200 mg of RMC-4630 twice weekly (BIW) on D1D2 of each week in a 21-day cycle and Sotorasib 960 mg once daily (QD) in a 21-day cycle. The 140mg and 200mg dose levels were explored at the safety run-in stage, and after completion of the safety run-in (DLT clearance) of both dose levels, additional patients were enrolled at both dose levels for the purpose of dose optimization before selecting the final expansion dose. Therefore, both the 140mg and 200mg dose levels included patients in the safety-run in and dose optimization. After that, 200mg was identified as the RP2D dose, which moved to the expansion phase. Statistical analysis for all sections in the results was performed for all treated patients by dose level, i.e., 140mg vs 200mg. For patients enrolled at the RP2D dose level of 200mg, analysis was further performed based on mutation status, i.e., cohorts 1 vs 2.
OG001	RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD

Secondary

Incidence, Nature and Severity of TEAEs, SAEs

Characterization of the safety, tolerability of RMC-4630 in combination with sotorasib for patients with KRASG12C-mutant NSCLC after failure of prior standard therapy. The specifics of the incidence, nature and severity data can be found under the Adverse Events section.

Posted

Number

participants

31 months

ID	Title	Description
OG000	RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD	The two arms have been broken down per dose level rather than by phase or cohort per the CSR, which is provided to FDA and not uploaded to ct.gov. Participants were administered 140 or 200 mg of RMC-4630 twice weekly (BIW) on D1D2 of each week in a 21-day cycle and Sotorasib 960 mg once daily (QD) in a 21-day cycle. The 140mg and 200mg dose levels were explored at the safety run-in stage, and after completion of the safety run-in (DLT clearance) of both dose levels, additional patients were enrolled at both dose levels for the purpose of dose optimization before selecting the final expansion dose. Therefore, both the 140mg and 200mg dose levels included patients in the safety-run in and dose optimization. After that, 200mg was identified as the RP2D dose, which moved to the expansion phase. Statistical analysis for all sections in the results was performed for all treated patients by dose level, i.e., 140mg vs 200mg. For patients enrolled at the RP2D dose level of 200mg, analysis was further performed based on mutation status, i.e., cohorts 1 vs 2.
OG001	RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD	The two arms have been broken down per dose level rather than by phase or cohort per the CSR, which is provided to FDA and not uploaded to ct.gov. Participants were administered 140 or 200 mg of RMC-4630 twice weekly (BIW) on D1D2 of each week in a 21-day cycle and Sotorasib 960 mg once daily (QD) in a 21-day cycle. The 140mg and 200mg dose levels were explored at the safety run-in stage, and after completion of the safety run-in (DLT clearance) of both dose levels, additional patients were enrolled at both dose levels for the purpose of dose optimization before selecting the final expansion dose. Therefore, both the 140mg and 200mg dose levels included patients in the safety-run in and dose optimization. After that, 200mg was identified as the RP2D dose, which moved to the expansion phase. Statistical analysis for all sections in the results was performed for all treated patients by dose level, i.e., 140mg vs 200mg. For patients enrolled at the RP2D dose level of 200mg, analysis was further performed based on mutation status, i.e., cohorts 1 vs 2.	3	4	3	4	4	4
EG001	RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD	The two arms have been broken down per dose level rather than by phase or cohort per the CSR, which is provided to FDA and not uploaded to ct.gov. Participants were administered 140 or 200 mg of RMC-4630 twice weekly (BIW) on D1D2 of each week in a 21-day cycle and Sotorasib 960 mg once daily (QD) in a 21-day cycle. The 140mg and 200mg dose levels were explored at the safety run-in stage, and after completion of the safety run-in (DLT clearance) of both dose levels, additional patients were enrolled at both dose levels for the purpose of dose optimization before selecting the final expansion dose. Therefore, both the 140mg and 200mg dose levels included patients in the safety-run in and dose optimization. After that, 200mg was identified as the RP2D dose, which moved to the expansion phase. Statistical analysis for all sections in the results was performed for all treated patients by dose level, i.e., 140mg vs 200mg. For patients enrolled at the RP2D dose level of 200mg, analysis was further performed based on mutation status, i.e., cohorts 1 vs 2.	21	43	43	43	43	43

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial fibrillation	Cardiac disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Myocardial infarction	Cardiac disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0012 affected43 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Catheter site pain	General disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Oedema peripheral	General disorders	MedDRA (23.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected43 at risk
Perforated ulcer	General disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Drug-induced liver injury	Hepatobiliary disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0013 affected43 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0012 affected43 at risk
Acute hepatic failure	Hepatobiliary disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Bile duct stenosis	Hepatobiliary disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Cholangitis	Hepatobiliary disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Jaundice	Hepatobiliary disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Pneumonia	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0001 affected4 at risk EG0014 affected43 at risk
Diverticulitis	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0012 affected43 at risk
Bacterial sepsis	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Bronchitis	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
COVID-19	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Clostridium difficile infection	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Infective exacerbation of chronic obstructive airways disease	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Influenza	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Sepsis	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Breast angiosarcoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Cerebral infarction	Nervous system disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0001 affected4 at risk EG0012 affected43 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0012 affected43 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0012 affected43 at risk
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Pulmonary arterial hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0011 affected43 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG00112 affected43 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0013 affected43 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0003 affected4 at risk EG00127 affected43 at risk
Nausea	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0003 affected4 at risk EG0018 affected43 at risk
Vomiting	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0001 affected4 at risk EG0015 affected43 at risk
Constipation	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0014 affected43 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0001 affected4 at risk EG0013 affected43 at risk
Gastroesophageal reflux disease	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0014 affected43 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0013 affected43 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0013 affected43 at risk
Stomatitis	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0013 affected43 at risk
Oedema peripheral	General disorders	MedDRA (23.0)	Systematic Assessment	EG0002 affected4 at risk EG00111 affected43 at risk
Fatigue	General disorders	MedDRA (23.0)	Systematic Assessment	EG0002 affected4 at risk EG0017 affected43 at risk
Pyrexia	General disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0016 affected43 at risk
Influenza like illness	General disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0014 affected43 at risk
Face oedema	General disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0013 affected43 at risk
Asthenia	General disorders	MedDRA (23.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected43 at risk
Drug-induced liver injury	Hepatobiliary disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0013 affected43 at risk
Pneumonia	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0001 affected4 at risk EG0016 affected43 at risk
Bronchitis	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0015 affected43 at risk
COVID-19	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0015 affected43 at risk
Bacteraemia	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected43 at risk
Alanine aminotransferase increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0003 affected4 at risk EG00120 affected43 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0003 affected4 at risk EG00119 affected43 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0002 affected4 at risk EG00114 affected43 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0001 affected4 at risk EG00112 affected43 at risk
Blood bilirubin increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0015 affected43 at risk
Lipase increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0014 affected43 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0013 affected43 at risk
Blood creatinine increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0013 affected43 at risk
C-reactive protein increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0013 affected43 at risk
Platelet count decreased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0013 affected43 at risk
Weight decreased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected43 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (23.0)	Systematic Assessment	EG0001 affected4 at risk EG0018 affected43 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (23.0)	Systematic Assessment	EG0001 affected4 at risk EG0014 affected43 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA (23.0)	Systematic Assessment	EG0001 affected4 at risk EG0014 affected43 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (23.0)	Systematic Assessment	EG0001 affected4 at risk EG0013 affected43 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (23.0)	Systematic Assessment	EG0001 affected4 at risk EG0013 affected43 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0013 affected43 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0014 affected43 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0013 affected43 at risk
Dizziness	Nervous system disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0014 affected43 at risk
Headache	Nervous system disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0014 affected43 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA (23.0)	Systematic Assessment	EG0001 affected4 at risk EG0011 affected43 at risk
Dysgeusia	Nervous system disorders	MedDRA (23.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected43 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0002 affected4 at risk EG00110 affected43 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0018 affected43 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0014 affected43 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0014 affected43 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0001 affected4 at risk EG0012 affected43 at risk
Respiratory acidosis	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0001 affected4 at risk EG0010 affected43 at risk
Pruritis	Skin and subcutaneous tissue disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected4 at risk EG0017 affected43 at risk

ID	Term
D002289	Carcinoma, Non-Small-Cell Lung
D009477	Hereditary Sensory and Autonomic Neuropathies
D002277	Carcinoma
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D002283	Carcinoma, Bronchogenic
D013899	Thoracic Neoplasms
D009421	Nervous System Malformations
D009422	Nervous System Diseases
D020271	Heredodegenerative Disorders, Nervous System
D019636	Neurodegenerative Diseases
D011115	Polyneuropathies
D010523	Peripheral Nervous System Diseases
D009468	Neuromuscular Diseases
D000013	Congenital Abnormalities
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D030342	Genetic Diseases, Inborn
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D001982	Bronchial Diseases