Non-small Cell Lung Cancer
Conditions
Keywords
Non-small cell lung cancer, KRAS p.G12C, Sotorasib, AMG 510
Brief summary
The main objective of this study is to evaluate the tumor objective response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in participants who receive sotorasib at either 960 mg daily or 240 mg daily whose tumors are programmed death-ligand 1 (PD-L1) Tumor Proportion Score (TPS) \< 1% and/or harbor a serine/threonine kinase 11 (STK11) co-mutation, in a subgroup of participants with PD-L1 \< 1% and in a subgroup of participants with STK11 co-mutation.
Interventions
DRUGSotorasib
Oral tablet
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult (= or \> 18 years old) with NSCLC * Untreated Stage IV metastatic disease. Participants who received adjuvant or neoadjuvant anti-tumor therapy are eligible if the adjuvant/neoadjuvant therapy was completed greater than 12 months prior to the development of metastatic stage IV disease * Pathologically documented metastatic NSCLC with KRAS G12C mutation (local confirmation) * Programmed death-ligand 1 (PD-L1) TPS Score \< 1% and/or serine/threonine kinase 11 (STK11) co-mutation (local confirmation) * Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 * No active brain metastases * Measurable disease per investigator interpretation using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
Exclusion criteria
* Mixed small-cell lung cancer and NSCLC histology * Myocardial Infarction within 6 months of study Day 1 * Use of proton-pump inhibitors (PPIs), histamine (H2) receptor antagonists (H2RA), strong inducers of cytochrome P450 (CYP) 3A4 (CYP3A4) or known CYP3A4 sensitive substrates or P-gp substrates * Therapeutic or palliative radiation therapy within 2 weeks of study day 1 * Unable to take oral medication * Unable to receive both iodinated contrast for computed tomography (CT) scans and gadolinium contrast for magnetic resonance imagine (MRI) scans
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Blinded Independent Central Review (BICR) | From the first dose of trial drug until min (last dose + 30 days, end of trial [EOT]); median [min, max] duration was 5.32 [0.8, 30.9] months | Objective response was defined as best overall response (BOR) of complete response (CR) or partial response (PR), as defined by RECIST 1.1. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 mm. PR was defined as at least a 30% decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters. Progressive disease (PD) was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. Responses were assessed based on BICR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) Per RECIST Version 1.1 as Assessed by BICR | From randomization until EOT; median [min, max] time on trial was 9.72 [0.8, 38.0] months | DCR was defined as the percentage of participants with an OR or stable disease (SD) per RECIST v1.1. CR: disappearance of all target lesions. All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to \<10 mm. PR: at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (this includes baseline sum if that is the smallest on study). |
| Duration of Response (DOR) Per RECIST Version 1.1 as Assessed by BICR | From randomization until EOT; median [min, max] time on trial was 9.72 [0.8, 38.0] months | DOR was defined as time from the first documentation of OR subsequently confirmed until the first documentation of PD or death due to any cause, whichever comes first. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (target or non-target) must have a reduction in their short axis \<10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. |
| Time to Response (TTR) Per RECIST Version 1.1 as Assessed by BICR | From randomization until EOT; median [min, max] time on trial was 9.72 [0.8, 38.0] months | TTR was defined as time from first dose date to the first documentation of PR or CR subsequently confirmed. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. |
| Progression-free Survival (PFS) as Assessed by BICR | From randomization until EOT; median [min, max] time on trial was 9.72 [0.8, 38.0] months | PFS by BICR was defined as the time from first dose date to disease progression or death due to any cause (whichever comes first). PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the baseline SOD of target lesions. |
| Overall Survival (OS) | From randomization until EOT; median [min, max] time on trial was 9.72 [0.8, 38.0] months | OS was defined as the time from first dose date until event of death due to any cause. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-related TEAEs | From the first dose of trial drug until min (last dose + 30 days, EOT); median [min, max] duration was 5.32 [0.8, 30.9] months | TEAEs are AEs starting on or after the first dose of sotorasib as determined by the flag indicating if the AE started prior to the first dose on the Events case report form (CRF) and up to and including 30 days after the last dose of sotorasib or the EOT date, whichever is earlier. A treatment-related TEAE is any TEAE with the relationship flag on the events CRF indicating there is a reasonable possibility that the event may have been caused by investigational medicinal product. Clinically significant changes in vital signs, electrocardiograms (ECGs), and clinical laboratory tests were included as TEAEs. |
| Plasma Concentration of Sotorasib | Cycles 1 and 2: Day 1 pre-dose and 1 hour post-dose; Cycles 3, 4 and, 5: Day 1 pre-dose (cycle length = 21 days) | Blood samples were collected at specified timepoints. |
Countries
Belgium, Denmark, France, Germany, Italy, Netherlands, Spain, Sweden, Turkey (Türkiye), United States
Contacts
STUDY_DIRECTORMD
Amgen
Participant flow
Recruitment details
A total of 42 participants were enrolled across 17 trial centers in the United States and Europe from January 2022 to May 2025.
Pre-assignment details
Participants received sotorasib at either 960 mg and 240 mg orally, once daily (QD). This trial was discontinued for strategic reasons.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 66.5 years STANDARD_DEVIATION 9.8 |
| Race/Ethnicity, Customized Not Hispanic or Latino | 42 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 41 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 15 / 21 | 16 / 21 |
| other Total, other adverse events | 18 / 21 | 20 / 21 |
| serious Total, serious adverse events | 9 / 21 | 9 / 21 |
Outcome results
None listed