TY - JOUR
T1 - Adagrasib in Advanced Solid Tumors Harboring a KRAS G12CMutation
AU - Bekaii-Saab, Tanios S.
AU - Yaeger, Rona
AU - Spira, Alexander I.
AU - Pelster, Meredith S.
AU - Sabari, Joshua K.
AU - Hafez, Navid
AU - Barve, Minal
AU - Velastegui, Karen
AU - Yan, Xiaohong
AU - Shetty, Aditya
AU - Der-Torossian, Hirak
AU - Pant, Shubham
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2023/9/1
Y1 - 2023/9/1
N2 - PURPOSEAdagrasib, a KRASG12C inhibitor, has demonstrated clinical activity in patients with KRASG12C-mutated non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). KRASG12C mutations occur rarely in other solid tumor types. We report evaluation of the clinical activity and safety of adagrasib in patients with other solid tumors harboring a KRASG12C mutation.METHODSIn this phase II cohort of the KRYSTAL-1 study (ClinicalTrials.gov identifier: NCT03785249; phase Ib cohort), we evaluated adagrasib (600 mg orally twice daily) in patients with KRASG12C-mutated advanced solid tumors (excluding NSCLC and CRC). The primary end point was objective response rate. Secondary end points included duration of response, progression-free survival (PFS), overall survival, and safety.RESULTSAs of October 1, 2022, 64 patients with KRASG12C-mutated solid tumors were enrolled and 63 patients treated (median follow-up, 16.8 months). The median number of prior lines of systemic therapy was 2. Among 57 patients with measurable disease at baseline, objective responses were observed in 20 (35.1%) patients (all partial responses), including 7/21 (33.3%) responses in pancreatic and 5/12 (41.7%) in biliary tract cancers. The median duration of response was 5.3 months (95% CI, 2.8 to 7.3) and median PFS was 7.4 months (95% CI, 5.3 to 8.6). Treatment-related adverse events (TRAEs) of any grade were observed in 96.8% of patients and grade 3-4 in 27.0%; there were no grade 5 TRAEs. TRAEs did not lead to treatment discontinuation in any patients.CONCLUSIONAdagrasib demonstrates encouraging clinical activity and is well tolerated in this rare cohort of pretreated patients with KRASG12C-mutated solid tumors.
AB - PURPOSEAdagrasib, a KRASG12C inhibitor, has demonstrated clinical activity in patients with KRASG12C-mutated non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). KRASG12C mutations occur rarely in other solid tumor types. We report evaluation of the clinical activity and safety of adagrasib in patients with other solid tumors harboring a KRASG12C mutation.METHODSIn this phase II cohort of the KRYSTAL-1 study (ClinicalTrials.gov identifier: NCT03785249; phase Ib cohort), we evaluated adagrasib (600 mg orally twice daily) in patients with KRASG12C-mutated advanced solid tumors (excluding NSCLC and CRC). The primary end point was objective response rate. Secondary end points included duration of response, progression-free survival (PFS), overall survival, and safety.RESULTSAs of October 1, 2022, 64 patients with KRASG12C-mutated solid tumors were enrolled and 63 patients treated (median follow-up, 16.8 months). The median number of prior lines of systemic therapy was 2. Among 57 patients with measurable disease at baseline, objective responses were observed in 20 (35.1%) patients (all partial responses), including 7/21 (33.3%) responses in pancreatic and 5/12 (41.7%) in biliary tract cancers. The median duration of response was 5.3 months (95% CI, 2.8 to 7.3) and median PFS was 7.4 months (95% CI, 5.3 to 8.6). Treatment-related adverse events (TRAEs) of any grade were observed in 96.8% of patients and grade 3-4 in 27.0%; there were no grade 5 TRAEs. TRAEs did not lead to treatment discontinuation in any patients.CONCLUSIONAdagrasib demonstrates encouraging clinical activity and is well tolerated in this rare cohort of pretreated patients with KRASG12C-mutated solid tumors.
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U2 - 10.1200/JCO.23.00434
DO - 10.1200/JCO.23.00434
M3 - Article
C2 - 37099736
AN - SCOPUS:85163506267
SN - 0732-183X
VL - 41
SP - 4097
EP - 4106
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 25
ER -