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KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors.

Authors :
Hong, David S
Hong, David S
Fakih, Marwan G
Strickler, John H
Desai, Jayesh
Durm, Gregory A
Shapiro, Geoffrey I
Falchook, Gerald S
Price, Timothy J
Sacher, Adrian
Denlinger, Crystal S
Bang, Yung-Jue
Dy, Grace K
Krauss, John C
Kuboki, Yasutoshi
Kuo, James C
Coveler, Andrew L
Park, Keunchil
Kim, Tae Won
Barlesi, Fabrice
Munster, Pamela N
Ramalingam, Suresh S
Burns, Timothy F
Meric-Bernstam, Funda
Henary, Haby
Ngang, Jude
Ngarmchamnanrith, Gataree
Kim, June
Houk, Brett E
Canon, Jude
Lipford, J Russell
Friberg, Gregory
Lito, Piro
Govindan, Ramaswamy
Li, Bob T
Hong, David S
Hong, David S
Fakih, Marwan G
Strickler, John H
Desai, Jayesh
Durm, Gregory A
Shapiro, Geoffrey I
Falchook, Gerald S
Price, Timothy J
Sacher, Adrian
Denlinger, Crystal S
Bang, Yung-Jue
Dy, Grace K
Krauss, John C
Kuboki, Yasutoshi
Kuo, James C
Coveler, Andrew L
Park, Keunchil
Kim, Tae Won
Barlesi, Fabrice
Munster, Pamela N
Ramalingam, Suresh S
Burns, Timothy F
Meric-Bernstam, Funda
Henary, Haby
Ngang, Jude
Ngarmchamnanrith, Gataree
Kim, June
Houk, Brett E
Canon, Jude
Lipford, J Russell
Friberg, Gregory
Lito, Piro
Govindan, Ramaswamy
Li, Bob T
Source :
The New England journal of medicine; vol 383, iss 13, 1207-1217; 0028-4793
Publication Year :
2020

Abstract

BackgroundNo therapies for targeting KRAS mutations in cancer have been approved. The KRAS p.G12C mutation occurs in 13% of non-small-cell lung cancers (NSCLCs) and in 1 to 3% of colorectal cancers and other cancers. Sotorasib is a small molecule that selectively and irreversibly targets KRASG12C.MethodsWe conducted a phase 1 trial of sotorasib in patients with advanced solid tumors harboring the KRAS p.G12C mutation. Patients received sotorasib orally once daily. The primary end point was safety. Key secondary end points were pharmacokinetics and objective response, as assessed according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.ResultsA total of 129 patients (59 with NSCLC, 42 with colorectal cancer, and 28 with other tumors) were included in dose escalation and expansion cohorts. Patients had received a median of 3 (range, 0 to 11) previous lines of anticancer therapies for metastatic disease. No dose-limiting toxic effects or treatment-related deaths were observed. A total of 73 patients (56.6%) had treatment-related adverse events; 15 patients (11.6%) had grade 3 or 4 events. In the subgroup with NSCLC, 32.2% (19 patients) had a confirmed objective response (complete or partial response) and 88.1% (52 patients) had disease control (objective response or stable disease); the median progression-free survival was 6.3 months (range, 0.0+ to 14.9 [with + indicating that the value includes patient data that were censored at data cutoff]). In the subgroup with colorectal cancer, 7.1% (3 patients) had a confirmed response, and 73.8% (31 patients) had disease control; the median progression-free survival was 4.0 months (range, 0.0+ to 11.1+). Responses were also observed in patients with pancreatic, endometrial, and appendiceal cancers and melanoma.ConclusionsSotorasib showed encouraging anticancer activity in patients with heavily pretreated advanced solid tumors harboring the KRAS p.G12C mutation. Grade 3 or 4 treatment-related toxic effect

Details

Database :
OAIster
Journal :
The New England journal of medicine; vol 383, iss 13, 1207-1217; 0028-4793
Notes :
application/pdf, The New England journal of medicine vol 383, iss 13, 1207-1217 0028-4793
Publication Type :
Electronic Resource
Accession number :
edsoai.on1391598187
Document Type :
Electronic Resource