Adagrasib in Advanced Solid Tumors Harboring a KRASG12C Mutation

  • J Clin Oncol. 2023 Sep 1;41(25):4097-4106. doi: 10.1200/JCO.23.00434.
Tanios S Bekaii-Saab  1 ,  Rona Yaeger  2 ,  Alexander I Spira  3  4  5 ,  Meredith S Pelster  6 ,  Joshua K Sabari  7 ,  Navid Hafez  8 ,  Minal Barve  9 ,  Karen Velastegui  10 ,  Xiaohong Yan  10 ,  Aditya Shetty  10 ,  Hirak Der-Torossian  10 ,  Shubham Pant  11
Affiliations
  • 1. Department of Medical Oncology and Hematology, Mayo Clinic, Scottsdale, AZ.
  • 2. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
  • 3. Virginia Cancer Specialists, Fairfax, VA.
  • 4. NEXT Oncology, Fairfax, VA.
  • 5. US Oncology Research, The Woodlands, TX.
  • 6. Sarah Cannon Research Institute, Tennessee Oncology, Nashville, TN.
  • 7. Perlmutter Cancer Center, New York University Langone Health, New York, NY.
  • 8. Yale Cancer Center, New Haven, CT.
  • 9. Mary Crowley Cancer Research, Dallas, TX.
  • 10. Mirati Therapeutics, Inc, San Diego, CA.
  • 11. The University of Texas MD Anderson Cancer Center, Houston, TX.
PMID: 37099736 DOI: 10.1200/JCO.23.00434
Abstract

Purpose: 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.

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 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.

Results: As 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.

Conclusion: Adagrasib demonstrates encouraging clinical activity and is well tolerated in this rare cohort of pretreated patients with KRASG12C-mutated solid Tumors.