Dataset Information

Adagrasib in Advanced Solid Tumors Harboring a KRAS^G12C Mutation.

ABSTRACT:

Purpose

Adagrasib, a KRAS^G12C inhibitor, has demonstrated clinical activity in patients with KRAS^G12C-mutated non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). KRAS^G12C 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 KRAS^G12C mutation.

Methods

In 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 KRAS^G12C-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.

Results

As of October 1, 2022, 64 patients with KRAS^G12C-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.

Conclusion

Adagrasib demonstrates encouraging clinical activity and is well tolerated in this rare cohort of pretreated patients with KRAS^G12C-mutated solid tumors.

SUBMITTER: Bekaii-Saab TS

PROVIDER: S-EPMC10852394 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Adagrasib in Advanced Solid Tumors Harboring a KRASG12C Mutation.

Bekaii-Saab Tanios S TS Yaeger Rona R Spira Alexander I AI Pelster Meredith S MS Sabari Joshua K JK Hafez Navid N Barve Minal M Velastegui Karen K Yan Xiaohong X Shetty Aditya A Der-Torossian Hirak H Pant Shubham S

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20230426 25

<h4>Purpose</h4>Adagrasib, 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.<h4>Methods</h4>In this phase II coh ...[more]

PMID: 37099736

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