Non-Small Cell Lung Cancer
Conditions
Keywords
SHP2, NSCLC, KRAS G12C, BRAF Class 1/2/unclassified, KRAS amplification, KRAS mutation, STK11/LKB1, KEAP1, PIK3CA, ATRX, BRCA2, carcinoma, non-small lung cancer, bronchial neoplasms, lung neoplasms, respiratory tract neoplasms, neoplasms by site, neoplasms, lung diseases, respiratory tract diseases
Brief summary
The purpose of this study is to evaluate the antitumor effects of sotorasib and RMC-4630 in subjects with KRASG12C mutant NSCLC
Detailed description
This is a phase 2 multicenter, open-label study evaluating the efficacy, safety, tolerability, and pharmacokinetics (PK) of RMC-4630 in combination with sotorasib in subjects with KRASG12C mutant NSCLC after failure of prior standard therapies.
Interventions
DRUGRMC-4630
RMC-4630 administered orally as a capsule
DRUGSotorasib
Sotorasib administered orally as a tablet
Sponsors
Sanofi
Amgen
Revolution Medicines, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) as Assessed Per RECIST v1.1 | 31 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinically Significant Changes in Laboratory Tests | 31 months | Characterization of the safety, tolerability of RMC-4630 in combination with sotorasib for subjects with KRASG12C mutant NSCLC after failure of prior standard therapy |
| Clinically Significant Changes in ECGs | 31 months | Characterization of the safety, tolerability of RMC-4630 in combination with sotorasib for subjects with KRASG12C mutant NSCLC after failure of prior standard therapy |
| Trough and Approximate Peak Concentrations of RMC-4630 | 31 months | Characterization of PK of RMC-4630 in combination with sotorasib for subjects with KRASG12C mutant NSCLC. |
| Trough and Approximate Peak Concentrations of Sotorasib | 31 months | Characterization of PK of RMC-4630 in combination with Sotorasib for subjects with KRASG12C mutant NSCLC |
| Clinically Significant Changes in Vital Signs | 31 months | Characterization of the safety, tolerability of RMC-4630 in combination with sotorasib for subjects with KRASG12C mutant NSCLC after failure of prior standard therapy |
| Disease Control Rate (DCR) as Assessed Per RECIST v.1.1 | 31 months | 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 |
| Progression-free Survival (PFS) as Assessed Per RECIST v1.1 | 31 months | 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 |
| Overall Survival (OS) | 31 months | 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 |
| Incidence, Nature and Severity of TEAEs, SAEs | 31 months | 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. |
| Duration of Response (DOR) as Assessed Per RECIST v1.1 | 31 months | 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 |
Countries
Australia, Canada, France, Germany, Italy, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Pre-assignment details
This Phase 2 study (RMC-4630-03) had a safety run-in period in which RMC-4630 was administered at 140 mg 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 as the starting dose with the option of escalating to RMC-4630 200 mg BIW on D1D2 of each week in a 21-day cycle. Patients were evaluated for dose limiting toxicities (DLTs).
Participants by arm
| Arm | Count |
|---|---|
| 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. | 4 |
| 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. | 43 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Agreed between patient and PI as safety follow up is not for benefit of the patient | 0 | 1 |
| Overall Study | Death | 1 | 21 |
| Overall Study | Due to AE#17 - Angiosarcoma of the breast with possible relation to study drug | 0 | 1 |
| Overall Study | Physician discretion due to subject progression | 0 | 1 |
| Overall Study | PI's decision that there is no benefit from LTFU | 0 | 6 |
| Overall Study | Sponsor amended protocol to terminate Long Term Follow Up (LTFU) | 0 | 3 |
| Overall Study | Sponsor's Decision to Terminate the Study | 0 | 3 |
| Overall Study | Withdrawal by Subject | 3 | 4 |
Baseline characteristics
| Characteristic | RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD | RMC-4630 200 mg D1D2 + Sotorasib 960 mg QD | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 20 Participants | 23 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 23 Participants | 24 Participants |
| Race/Ethnicity, Customized Ethnicity: Hispanic or Latino | 0 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized Ethnicity: Missing/Not Reported | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Ethnicity: Not Hispanic or Latino | 4 participants | 40 participants | 44 participants |
| Race/Ethnicity, Customized Race: American Indian or Alaska Native | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Race: Asian | 1 participants | 8 participants | 9 participants |
| Race/Ethnicity, Customized Race: Black or African American | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Race: Missing/Not Reported | 0 participants | 4 participants | 4 participants |
| Race/Ethnicity, Customized Race: Native Hawaiian or Other Pacific Islander | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Race: Other | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Race: White | 3 participants | 31 participants | 34 participants |
| Sex: Female, Male Female | 2 Participants | 25 Participants | 27 Participants |
| Sex: Female, Male Male | 2 Participants | 18 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 4 | 21 / 43 |
| other Total, other adverse events | 4 / 4 | 43 / 43 |
| serious Total, serious adverse events | 3 / 4 | 43 / 43 |
Outcome results
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.
Time frame: 31 months
Population: Objective Response Rate (%) is defined as the proportion of patients with Best Overall Response of confirmed CR, or PR.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD | Objective Response Rate (ORR) as Assessed Per RECIST v1.1 | 0 Participants |
| RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD | Objective Response Rate (ORR) as Assessed Per RECIST v1.1 | 11 Participants |
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
Time frame: 31 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD | Clinically Significant Changes in ECGs | 0 Participants |
| RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD | Clinically Significant Changes in ECGs | 0 Participants |
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
Time frame: 31 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD | Clinically Significant Changes in Laboratory Tests | Grade 3 Aspartate Aminotransferase Increased | 2 Participants |
| RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD | Clinically Significant Changes in Laboratory Tests | Grade 4 Alanine Aminotransferase Increased | 0 Participants |
| RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD | Clinically Significant Changes in Laboratory Tests | Grade 3 Bilirubin Increased | 0 Participants |
| RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD | Clinically Significant Changes in Laboratory Tests | Grade 4 Aspartate Aminotransferase Increased | 0 Participants |
| RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD | Clinically Significant Changes in Laboratory Tests | Grade 3 Alanine Aminotransferase Increased | 1 Participants |
| RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD | Clinically Significant Changes in Laboratory Tests | Grade 4 Aspartate Aminotransferase Increased | 2 Participants |
| RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD | Clinically Significant Changes in Laboratory Tests | Grade 3 Alanine Aminotransferase Increased | 5 Participants |
| RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD | Clinically Significant Changes in Laboratory Tests | Grade 3 Aspartate Aminotransferase Increased | 5 Participants |
| RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD | Clinically Significant Changes in Laboratory Tests | Grade 3 Bilirubin Increased | 5 Participants |
| RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD | Clinically Significant Changes in Laboratory Tests | Grade 4 Alanine Aminotransferase Increased | 2 Participants |
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
Time frame: 31 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD | Clinically Significant Changes in Vital Signs | 0 Participants |
| RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD | Clinically Significant Changes in Vital Signs | 0 Participants |
Secondary
Disease Control Rate (DCR) as Assessed Per RECIST v.1.1
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
Time frame: 31 months
Population: Disease Control Rate (%) is defined as the proportion of subjects with best overall response of CR, PR, or stable disease
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD | Disease Control Rate (DCR) as Assessed Per RECIST v.1.1 | 3 Participants |
| RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD | Disease Control Rate (DCR) as Assessed Per RECIST v.1.1 | 34 Participants |
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
Time frame: 31 months
Population: Duration of Response (DOR) Based on Investigator Assessments (Subjects with Confirmed CR or PR Responders only).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD | Duration of Response (DOR) as Assessed Per RECIST v1.1 | 12.19 months |
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.
Time frame: 31 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD | Incidence, Nature and Severity of TEAEs, SAEs | Serious Adverse Events | 3 participants |
| RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD | Incidence, Nature and Severity of TEAEs, SAEs | Other (Not Including Serious) Adverse Events | 4 participants |
| RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD | Incidence, Nature and Severity of TEAEs, SAEs | Serious Adverse Events | 43 participants |
| RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD | Incidence, Nature and Severity of TEAEs, SAEs | Other (Not Including Serious) Adverse Events | 43 participants |
Secondary
Overall Survival (OS)
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
Time frame: 31 months
Population: Summary of Overall Survival (OS) (All Treated Subjects).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD | Overall Survival (OS) | 5.80 months |
| RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD | Overall Survival (OS) | 12.45 months |
Secondary
Progression-free Survival (PFS) 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
Time frame: 31 months
Population: Summary of Progression-Free Survival (PFS) Based on Investigator Assessments (All Treated Subjects).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD | Progression-free Survival (PFS) as Assessed Per RECIST v1.1 | 2.64 months |
| RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD | Progression-free Survival (PFS) as Assessed Per RECIST v1.1 | 7.66 months |
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.
Time frame: 31 months
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD | Trough and Approximate Peak Concentrations of RMC-4630 | Cycle 1 Day 15 post-dose (2 hour +/- 10 minutes post-dose) | 187.64 ng/ml | Geometric Coefficient of Variation 106.19 |
| RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD | Trough and Approximate Peak Concentrations of RMC-4630 | Cycle 3 Day 1 pre-dose (within 1 hour pre-dose) | 82.40 ng/ml | Geometric Coefficient of Variation 166.3 |
| RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD | Trough and Approximate Peak Concentrations of RMC-4630 | Cycle 2 Day 1 pre-dose (within 1 hour pre-dose) | 24.75 ng/ml | Geometric Coefficient of Variation 269.94 |
| RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD | Trough and Approximate Peak Concentrations of RMC-4630 | Cycle 4 Day 1 pre-dose (within 1 hour pre-dose) | 33.48 ng/ml | Geometric Coefficient of Variation 535.67 |
| RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD | Trough and Approximate Peak Concentrations of RMC-4630 | Cycle 1 Day 15 pre-dose (within 1 hour pre-dose) | 21.04 ng/ml | Geometric Coefficient of Variation 138.51 |
| RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD | Trough and Approximate Peak Concentrations of RMC-4630 | Cycle 4 Day 1 pre-dose (within 1 hour pre-dose) | 14.67 ng/ml | Geometric Coefficient of Variation 128.88 |
| RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD | Trough and Approximate Peak Concentrations of RMC-4630 | Cycle 1 Day 15 pre-dose (within 1 hour pre-dose) | 27.55 ng/ml | Geometric Coefficient of Variation 127.22 |
| RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD | Trough and Approximate Peak Concentrations of RMC-4630 | Cycle 1 Day 15 post-dose (2 hour +/- 10 minutes post-dose) | 276.29 ng/ml | Geometric Coefficient of Variation 122.66 |
| RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD | Trough and Approximate Peak Concentrations of RMC-4630 | Cycle 2 Day 1 pre-dose (within 1 hour pre-dose) | 22.34 ng/ml | Geometric Coefficient of Variation 179.87 |
| RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD | Trough and Approximate Peak Concentrations of RMC-4630 | Cycle 3 Day 1 pre-dose (within 1 hour pre-dose) | 18.35 ng/ml | Geometric Coefficient of Variation 155.47 |
Secondary
Trough and Approximate Peak Concentrations of Sotorasib
Characterization of PK of RMC-4630 in combination with Sotorasib for subjects with KRASG12C mutant NSCLC
Time frame: 31 months
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD | Trough and Approximate Peak Concentrations of Sotorasib | Cycle 1 Day 15 post-dose (2 hour +/- 10 minutes post-dose) | 6009.3 ng/mL | Geometric Coefficient of Variation 119.2 |
| RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD | Trough and Approximate Peak Concentrations of Sotorasib | Cycle 3 Day 1 pre-dose (within 1 hour pre-dose) | 342.2 ng/mL | Geometric Coefficient of Variation 12146.3 |
| RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD | Trough and Approximate Peak Concentrations of Sotorasib | Cycle 2 Day 1 pre-dose (within 1 hour pre-dose) | 674.7 ng/mL | Geometric Coefficient of Variation 193.2 |
| RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD | Trough and Approximate Peak Concentrations of Sotorasib | Cycle 4 Day 1 pre-dose (within 1 hour pre-dose) | 803.5 ng/mL | Geometric Coefficient of Variation 152.3 |
| RMC-4630 140 mg BIW D1D2 + Sotorasib 960 mg QD | Trough and Approximate Peak Concentrations of Sotorasib | Cycle 1 Day 15 pre-dose (within 1 hour pre-dose) | 615.6 ng/mL | Geometric Coefficient of Variation 173.5 |
| RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD | Trough and Approximate Peak Concentrations of Sotorasib | Cycle 4 Day 1 pre-dose (within 1 hour pre-dose) | 404.5 ng/mL | Geometric Coefficient of Variation 367.3 |
| RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD | Trough and Approximate Peak Concentrations of Sotorasib | Cycle 1 Day 15 pre-dose (within 1 hour pre-dose) | 375.4 ng/mL | Geometric Coefficient of Variation 134.4 |
| RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD | Trough and Approximate Peak Concentrations of Sotorasib | Cycle 1 Day 15 post-dose (2 hour +/- 10 minutes post-dose) | 4603.3 ng/mL | Geometric Coefficient of Variation 77.3 |
| RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD | Trough and Approximate Peak Concentrations of Sotorasib | Cycle 2 Day 1 pre-dose (within 1 hour pre-dose) | 336.4 ng/mL | Geometric Coefficient of Variation 170.8 |
| RMC-4630 200 mg BIW D1D2 + Sotorasib 960 mg QD | Trough and Approximate Peak Concentrations of Sotorasib | Cycle 3 Day 1 pre-dose (within 1 hour pre-dose) | 190.3 ng/mL | Geometric Coefficient of Variation 125.7 |