KRAS p, G12c Mutated /Advanced Metastatic NSCLC
Conditions
Brief summary
A Phase 3 Study to Compare AMG 510 with Docetaxel in Non Small Cell Lung Cancer (NSCLC) subjects with KRAS p. G12c mutation
Interventions
DRUGAMG 510
21 day cycles
DRUGDocetaxel
21 day cycles
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Men or women greater than or equal to 18 years old. * ECOG ≤ 1 * Pathologically documented, previously treated, locally-advanced and unresectable or metastatic NSCLC with KRAS p.G12C mutation confirmed through central testing or have documentation of KRAS p.G12C mutation through Amgen Study 20190294 prior to enrollment
Exclusion criteria
* Active brain metastases * Myocardial infarction within 6 months of study day 1 * Gastrointestinal (GI) tract disease causing the inability to take oral medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Baseline up to primary analysis data cut-off date (02 August 2022); max time on study as of primary analysis data cut off was 24.3 months | PFS was defined as the time from randomization (baseline) until disease progression or death from any cause, whichever occurred first for all participants. Progression was based on blinded independent central review (BICR) of disease response per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). As pre-specified in the statistical analysis plan, for participants who crossed over from docetaxel to AMG 510, the participant's response post first progression or post crossover was not used for the primary analyses. Data are presented per original treatment randomized. |
Countries
Australia, Belgium, Brazil, Canada, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Japan, Netherlands, Poland, Portugal, Russia, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORMD
Amgen
Participant flow
Recruitment details
345 participants were enrolled at 148 centers in Europe, North America, Asia, Australia, and South America. The analyses presented in this results summary are based on the primary completion data. The primary completion data cut-off was 02 August 2022. The study is ongoing.
Pre-assignment details
Screening assessments were conducted within 28 days before Cycle 1 Day 1 (C1D1; where a cycle is 21 days). Participants were then randomized 1:1 to receive either AMG 510 or docetaxel, stratified by number of prior lines of therapy in advanced disease (1 vs 2 vs \> 2), race (Asian vs non-Asian), and history of central nervous system (CNS) involvement (present or absent).
Participants by arm
| Arm | Count |
|---|---|
| AMG 510 Participants with previously treated locally advanced and unresectable or metastatic NSCLC with centrally confirmed KRAS p.G12C mutation received 960 mg of AMG 510 orally via tablets QD in each 21 day cycle. | 171 |
| Docetaxel Participants with previously treated locally advanced and unresectable or metastatic NSCLC with centrally confirmed KRAS p.G12C mutation received 75 mg/m\^2 of docetaxel via intravenous (IV) infusion once every 3 weeks (Q3W) in each 21 day cycle. Participants who were determined to have radiological progression according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) by the investigator and progressive disease confirmed by independent central imaging review, could have switched to receive AMG 510. Alternatively, if an early efficacy of the study is noted by the data monitoring committee, crossover would be considered for all participants who randomized into the docetaxel arm (so that they are able to immediately receive AMG 510). | 174 |
| Total | 345 |
Baseline characteristics
| Characteristic | Docetaxel | Total | AMG 510 |
|---|---|---|---|
| Age, Continuous | 63.6 years STANDARD_DEVIATION 9.1 | 63.5 years STANDARD_DEVIATION 9.5 | 63.4 years STANDARD_DEVIATION 9.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 14 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 163 Participants | 328 Participants | 165 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 22 Participants | 43 Participants | 21 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 13 Participants | 5 Participants |
| Race (NIH/OMB) White | 144 Participants | 286 Participants | 142 Participants |
| Sex: Female, Male Female | 79 Participants | 141 Participants | 62 Participants |
| Sex: Female, Male Male | 95 Participants | 204 Participants | 109 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 78 / 174 | 109 / 171 | 17 / 46 |
| other Total, other adverse events | 129 / 151 | 151 / 169 | 35 / 46 |
| serious Total, serious adverse events | 67 / 151 | 91 / 169 | 26 / 46 |
Outcome results
Primary
Progression-free Survival (PFS)
PFS was defined as the time from randomization (baseline) until disease progression or death from any cause, whichever occurred first for all participants. Progression was based on blinded independent central review (BICR) of disease response per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). As pre-specified in the statistical analysis plan, for participants who crossed over from docetaxel to AMG 510, the participant's response post first progression or post crossover was not used for the primary analyses. Data are presented per original treatment randomized.
Time frame: Baseline up to primary analysis data cut-off date (02 August 2022); max time on study as of primary analysis data cut off was 24.3 months
Population: Measured in the Full Analysis Set (FAS), which included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AMG 510 | Progression-free Survival (PFS) | 5.62 months |
| Docetaxel | Progression-free Survival (PFS) | 4.47 months |
p-value: 0.00295% CI: [0.509, 0.864]Log Rank