Advanced Solid Tumors, Kirsten Rat Sarcoma (KRAS) pG12C Mutation
Conditions
Brief summary
To evaluate the safety and tolerability of sotorasib administered in investigational regimens in adult participants with KRAS p.G12C mutant advanced solid tumors.
Interventions
DRUGSotorasib
Sotorasib administered orally as a tablet.
DRUGTrametinib
Trametinib administered orally as a tablet.
DRUGRMC-4630
RMC-4630 administered orally as a capsule.
DRUGAfatinib
afatinib administered orally as a tablet.
DRUGPembrolizumab
pembrolizumab administered as an intravenous (IV) infusion.
DRUGPanitumumab
Panitumumab administered as an IV infusion.
DRUGCarboplatin, pemetrexed, docetaxel, paclitaxel
Carboplatin, pemetrexed, docetaxel administered as an IV infusion.
DRUGAtezolizumab
Atezolizumab administered as an IV injection.
DRUGPalbociclib
Palbociclib administered orally as a tablet.
DRUGMVASI® (bevacizumab-awwb)
MVASI® (bevacizumab-awwb) administered as an IV infusion.
DRUGTNO155
TNO155 administered orally as a capsule.
Chemotherapy combination of leucovorin administered as an IV injection, 5-fluorouracil (5-FU) administered as IV bolus injection or IV continuous infusion (depending on dose), and irinotecan administered as IV injection.
DRUGIV Chemotherapy (Regimen 2)
IV chemotherapy combination of leucovorin administered as an IV injection, 5-FU administered as IV bolus injection or IV continuous infusion (depending on dose), and oxaliplatin administered as IV injection.
DRUGBI 1701963
BI 1701963 administered orally
DRUGAMG 404
AMG 404 administered as an IV infusion.
DRUGEverolimus
Everolimus administered orally.
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
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. * Pathologically documented, locally-advanced or metastatic malignancy with, KRAS p.G12C mutation identified through molecular testing performed according to in-country requirements. In the United States, this test must be performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
Exclusion criteria
* Primary brain tumor. * Spinal cord compression, or untreated, or symptomatic, or active brain metastases, or leptomeningeal disease from non-brain tumors. * 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 |
|---|---|
| Number of Participants with Dose Limiting Toxicities (DLTs) | 12 Months |
| Number of Participants with Treatment-emergent Adverse Events (TEAEs) | 12 Months |
| Number of Participants with Treatment-related Adverse Events | 12 Months |
| Number of Participants with Clinically Significant Changes in Vital Signs | 12 Months |
| Number of Participants with Clinically Significant Changes in ECG Measurements | 12 Months |
| Number of Participants with Clinically Significant Changes in Laboratory Test Values | 12 Months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | 12 Months | — |
| Disease Control Rate | 12 Months | — |
| Duration of Response | 12 Months | — |
| Progression-free Survival | 12 Months | — |
| Duration of Stable Disease | 12 Months | — |
| Time to Response | 12 Months | — |
| Sotorasib Monotherapy Only: Intracranial Objective Response Rate | 12 Months | Intracranial objective response rate assessed per Response Assessment in Neuro-oncology Brain Metastases (RANO-BM). |
| Sotorasib Monotherapy Only: Intracranial Disease Control Rate | 12 Months | Intracranial disease control rate assessed per RANO-BM. |
| Sotorasib Monotherapy Only: Intracranial Duration of Response | 12 Months | Intracranial duration of response assessed per RANO-BM. |
| Sotorasib + EGFR Inhibitor +/- Chemotherapeutic Regimen Only: Quantification of Plasma Levels | 12 Months | — |
| Sotorasib Monotherapy Only: Intracranial Progression-free Survival (PFS) | 12 Months | Intracranial PFS assessed per RANO-BM. |
| Sotorasib Monotherapy Only: Non-intracranial Progression-free Survival (PFS) | 12 Months | Non-intracranial PFS assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. |
| Sotorasib Monotherapy Only: Overall Progression-free Survival (PFS) | 12 Months | Overall PFS assessed per RECIST 1.1 and RANO-BM. |
| Sotorasib + TNO155 Only: Best Overall Response | 12 Months | — |
| Sotorasib + Afatinib + Loperamide Only: Number of Participants with Treatment-emergent Adverse Events (TEAEs) | 12 Months | — |
| Sotorasib + Afatinib + Loperamide Only: Number of Participants with Treatment-related Adverse Events | 12 Months | — |
| Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in Vital Signs | 12 Months | — |
| Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in ECG Measurements | 12 Months | — |
| Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in Laboratory Test Values | 12 Months | — |
| Sotorasib Monotherapy Only: Time to Intracranial Radiation Therapy | 12 Months | — |
| Sotorasib + Afatinib + Loperamide Only: Number of Participants with Dose Limiting Toxicities (DLTs) | 12 Months | — |
| Overall Survival | 12 Months | — |
| Maximum Plasma Concentration (Cmax) | 12 Months | — |
| Time to Maximum Plasma Concentration (Tmax) | 12 Months | — |
| Area Under the Plasma Concentration-time Curve (AUC) | 12 Months | — |
Countries
Australia, Austria, Belgium, Canada, Germany, Italy, Japan, Netherlands, South Korea, Spain, Taiwan, United Kingdom, United States
Outcome results
None listed