Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
AMG 510 · 13 trials · 4 indications
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.
The pharmacokinetic (PK) parameters were determined using standard non-compartmental methods.
The PK parameters were determined using standard non-compartmental methods.
The PK parameters were determined using standard non-compartmental methods.
Blood samples were collected by venipuncture or cannulation for measurement of plasma concentrations of sotorasib. Plasma pharmacokinetic (PK) parameters of sotorasib were summarized per treatment received, regardless of treatment sequence, as pre-specified.
Blood samples were collected by venipuncture or cannulation for measurement of plasma concentrations of sotorasib. Plasma PK parameters of sotorasib were summarized per treatment received, regardless of treatment sequence, as pre-specified.
Blood samples were collected by venipuncture or cannulation for measurement of plasma concentrations of sotorasib. Plasma PK parameters of sotorasib were summarized per treatment received, regardless of treatment sequence, as pre-specified.
DLTs were defined as any of the following adverse events (AEs) where a relationship to sotorasib could not be ruled out. Hematological toxicity * febrile neutropenia * neutropenic infection * grade 4 neutropenia * grade ≥ 3 thrombocytopenia for \> 7 days * grade 3 thrombocytopenia with grade ≥ 2 bleeding * grade 4 thrombocytopenia * grade 4 anemia. Non-hematological toxicity * grade ≥ 4 vomiting or diarrhea * grade 3 diarrhea or grade 3 vomiting lasting more than 3 days despite optimal medical support * grade ≥ 3 nausea for 3 days or more despite optimal medical support * any other grade ≥ 3 adverse event.
An AE was any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. A TEAE was defined as an AE starting on or after first dose of study treatment. Treatment-related TEAEs were any TEAEs considered related to investigational product by the investigator. If relationship was missing, the event was assumed treatment-related. Clinically significant changes from the participant's baseline values in vital signs, 12-lead electrocardiograms, and clinical laboratory safety tests were reported as AEs.
Pharmacokinetic (PK) parameters were determined from the concentration-time profile using standard non-compartmental approaches and considering the profile over the complete sampling interval.
PK parameters were determined from the concentration-time profile using standard non-compartmental approaches and considering the profile over the complete sampling interval.
PK parameters were determined from the concentration-time profile using standard non-compartmental approaches and considering the profile over the complete sampling interval.
| Arm | Type | Description |
|---|---|---|
| AMG 510 | EXPERIMENTAL | - |
| Docetaxel | ACTIVE_COMPARATOR | - |
| Treatment Sequence ABC | EXPERIMENTAL | Participants will be administered sotorasib orally in the following order: Period 1 - as 1 tablet (test 1) Period 2 - as 2 tablets (reference) Period 3 - as 1 tablet (test 2) |
| Treatment Sequence BAC | EXPERIMENTAL | Participants will be administered sotorasib orally in the following order: Period 1 - as 2 tablets (reference) Period 2 - as 1 tablet (test 1) Period 3 - as 1 tablet (test 2) |
| Rosuvastatin alone | EXPERIMENTAL | - |
| Rosuvastatin + sotorasib | EXPERIMENTAL | - |
| AMG 510 + Omeprazole + Famotidine | EXPERIMENTAL | Participants will receive AMG 510 on Day 1, famotidine on Day 3, AMG 510 and famotidine on Day 4, omeprazole on Days 6 through 10, and omeprazole and AMG 510 on Day 11. |
| Treatment Arm | EXPERIMENTAL | Subjects will be enrolled and will receive AMG 510 PO QD. |
| AMG510 | EXPERIMENTAL | Each participant will receive a single oral dose of AMG510 on Day 1 after an overnight fast. |
| Treatment Sequence AB | EXPERIMENTAL | Participants will be administered AMG 510 in the following order: Period 1 (treatment A) - AMG 510 as oral tablets. Period 2 (treatment B) - AMG 510 as tablets dispersed in water. |
| Treatment Sequence BA | EXPERIMENTAL | Participants will be administered AMG 510 in the following order: Period 1 (treatment B) - AMG 510 as tablets dispersed in water. Period 2 (treatment A) - AMG 510 as oral tablets. |
| AMG 510 + Omeprazole | EXPERIMENTAL | Participants will receive AMG 510 on Day 1, daily doses of omeprazole on Days 4 to 8, and a single dose of both omeprazole and AMG 510 on Day 9. |
| AMG 510 + Itraconazole | EXPERIMENTAL | - |
| AMG 510 + Rifampin | EXPERIMENTAL | - |
| AMG 510 + Digoxin | EXPERIMENTAL | Participants will receive digoxin on Day 1 and both AMG 510 + digoxin on Day 7. |
| Name | Type | Description |
|---|---|---|
| AMG 510 | DRUG | 21 day cycles |
| Docetaxel | DRUG | 21 day cycles |
| Sotorasib | DRUG | Oral Tablet |
| Rosuvastatin | DRUG | Oral dose |
| Omeprazole | DRUG | Capsule |
| Famotidine | DRUG | Tablet |
| Itraconazole | DRUG | Oral capsule |
| Rifampin | DRUG | Oral capsule |
| Digoxin | DRUG | Oral tablet |
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 throu...