Sotorasib is a small molecule currently under investigation that is designed to specifically and irreversibly inhibit the KRASG12C protein.
Status
Recruiting
PHASE
Phase 1/2
CONDITION
Advanced solid tumors, including NSCLC
STUDY DRUG
Sotorasib alone or combined with another anti-cancer therapy
Status
Recruiting
PHASE
Phase 1b/2
CONDITION
Advanced solid tumors, including NSCLC
STUDY DRUG
Sotorasib and other anti-cancer therapies
Status
ACTIVE, NOT RECRUITING
PHASE
Phase 3
CONDITION
Non-small cell lung cancer
STUDY DRUG
Sotorasib or docetaxel
Status
Recruiting
PHASE
Phase 2
CONDITION
Metastatic NSCLC
STUDY DRUG
Sotorasib
Status
Recruiting
PHASE
Phase 3
CONDITION
Metastatic CRC
STUDY DRUG
Sotorasib plus panitumumab OR
Trifluridine and tipiracil OR
Regorafenib
KRAS G12C mutant advanced NSCLC, CRC, and other solid tumors
Phase 1: sotorasib monotherapy or combination therapy (sotorasib + PD-1/L1 inhibitor)
Phase 2: sotorasib monotherapy
Inclusion
Exclusion
*additional criteria apply
TEAEs, TRAEs, Number of grade ≥ 3 TEAEs, serious AEs, AEs of interest, clinically significant changes in vital signs, electrocardiograms, and clinical laboratory tests, DLT, ORR, DOR, DCR, PFS, duration of SD, TTR, OS
*Endpoints vary by study phase/part
Locally-advanced or metastatic malignancy that harbors a KRAS G12C mutation
Sotorasib orally once daily monotherapy or in combination with anticancer treatments. Anticancer treatments include:
Inclusion
Exclusion
*additional criteria apply
DLTs, TEAEs, TRAEs, and clinically significant changes in vital signs, ECGs, and clinical laboratory tests, and ORR
PK parameters of sotorasib and anti-cancer treatments, ORR, DOR, PFS, DCR, time to response and overall survival
CDK, Cyclin-dependent kinase; CRC, colorectal cancer; DCR, disease control rate; DLT, dose-limiting toxicity; DOR, duration of response; ECG, electrocardiogram; EGFR, epidermal growth factor receptor; ErbB, erythroblastic leukemia viral oncogene homolog; KRAS, Kirsten rat sarcoma; MEK, mitogen-activated protein kinase; mTOR, mammalian target of rapamycin; NSCLC, non-small cell lung cancer; ORR, objective response rate; PD-1, programmed cell death protein 1; PFS, progression-free survival; PK, pharmacokinetic; SD, stable disease; SHP2, src homology region 2-containing protein tyrosine phosphatase 2; TEAE, treatment-emergent adverse event; TKI, tyrosine kinase inhibitor; TRAE, treatment-related adverse event
Untreated stage IV NSCLC that harbors a KRAS G12C mutation
Sotorasib monotherapy (960mg or 240mg daily)
Inclusion
Exclusion
*additional criteria apply
Primary: ORR
Secondary: DCR; DOR; TTR; PFS; OS; TEAEs; TRAEs; Changes in vital signs, ECGs, and clinical laboratory tests
DCR, disease control rate; DOR, duration of response; ECG, electrocardiogram; ORR, objective response rate; OS, overall survival; PD-L1, programmed death-ligand 1; PFS, progression-free survival; STK11, serine/threonine kinase 11; TEAE, treatment-emergent adverse event; TPS, tumor proportion score, TRAE, treatment-related adverse event; TTR, time to response
Previously treated metastatic CRC that harbors a KRAS G12C mutation
Sotorasib plus panitumumab OR Trifluridine and tipiracil OR Regorafenib
Inclusion
Exclusion
*additional criteria apply
Primary: PFS
Secondary: OS, ORR, DOR, TTR, DCR, investigator-assessed ORR, investigator-assessed PFS
CRC, colorectal cancer; DCR, disease control rate; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; GI, gastrointestinal; IV, intravenous; KRAS, Kirsten rat sarcoma; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; RECIST, Response Evaluation Criteria In Solid Tumors; TTR, time to response
KRAS mutations can play a role in some of the most common cancers, including lung, colorectal, and pancreatic cancers. The KRAS G12C mutation is an oncogenic driver occurring in approximately 13% of non-squamous non-small cell lung cancer (NSCLC), and 1-3% of other solid tumors, such as colorectal cancer.1,2,3
Watch this video to learn more about how KRAS G12C mutations contribute to oncogenesis.
Amgen is investigating ways to target mutant KRAS. Recent scientific advancements have revealed a binding site in the inactive state of KRASG12C. The mutant cysteine resides next to a narrow surface pocket, the P2 pocket, providing a potential binding target for covalent inhibitors, such as sotorasib.4,5,6
References: 1. Cox AD, Fesik SW, Kimmelman AC, Luo J, Der CJ. Nat Rev Drug Discov. 2014;13(11):828-851. 2. Biernacka A, Tsongalis PD, Peterson JD, et al. Cancer Genet. 2016;209(5):195-198. 3. Neumann J, Zeindl-Eberhart E, Kirchner T, Jung A. Pathol Res Pract. 2009;205:858-862. 4. Ryan MB, Corcoran RB. Nat Rev Clin Oncol. 2018;15(11):709-720. 5. Lanman BA, Chen JJ, Liu L, et al. Cancer Res. 2019;79(suppl 13):abstract 4455. 6. Canon J, Rex K, Saiki AY, et al. Nature. 2019;575(7781):217-223.