KRYSTAL-12 Study of Adagrasib Meets Primary End Point in KRAS G12C NSCLC
The KRYSTAL-12 trial of adagrasib showed positive results for progression-free survival and tumor response in KRAS G12C-mutated non-small cell lung cancer.
Holographic concept of lung cancer display, lung disease: © catalin - stock.adobe.com
The phase 3 KRYSTAL-12 study (NCT04685135) investigating adagrasib (Krazati) for the treatment of patients with pretreated locally advanced or metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC) met its primary end point of progression-free survival (PFS), as well as its key secondary end point of overall response rate (ORR) as assessed by blinded independent central review (BICR) at the final analysis for these end points.1
The study remains ongoing to assess the additional key secondary end point of overall survival. The KRYSTAL-12 study, a confirmatory trial, showed that treatment with adagrasib led to a statistically significant and clinically meaningful benefit in PFS and ORR vs standard-of-care (SOC) chemotherapy when given in the second line or later. For safety, data was consistent with the known safety profile of the agent, and no new safety signals were observed.
A full evaluation of the available data is planned to be completed and shared with the scientific community at an upcoming medical conference. Further, these data will also be discussed with health authorities.
“Today’s news is an important reinforcement of the power of a targeted therapy for patients with locally advanced or metastatic KRAS G12C-mutated lung cancer. FDA approval of [adagrasib] in the US has allowed us to provide a new treatment option for these patients, and topline results of the KRYSTAL-12 confirmatory study will build greater trust in the medical and patient community,” said Abderrahim Oukessou, MD, vice president, global program lead of adagrasib at Bristol Myers Squibb, in a press release. “We are encouraged by the results from KRYSTAL-12 and look forward to helping more patients with KRAS G12C-mutated lung cancer.”
Adagrasib is a highly selective and potent oral small-molecule inhibitor of KRAS G12C. The agent works to sustain target inhibition. In December 2022, adagrasib was granted FDA accelerated approval for patients with KRAS G12C-mutated locally advanced or metastatic NSCLC who have received at least 1 prior systemic therapy. The agent has also shown promise in phase 2 trials across several tumor types, including advanced colorectal cancer (CRC), pancreatic cancer, and other solid tumors.
The FDA accepted for priority review the supplemental new drug application for adagrasib when given with cetuximab (Erbitux) for the treatment of patients with previously treated KRAS G12C-mutated locally advanced or metastatic CRC in February 2024, and a Prescription Drug User Fee Act target date was set for June 21, 2024.
About the KRYSTAL-12 Clinical Trial
The open-label, multicenter, randomized, phase 3 KRYSTAL-12 study is assessing adagrasib and comparing it with SOC chemotherapy alone for the treatment of patients with KRAS G12C-mutated NSCLC.2
The study enrolled 453 patients with a histologically or cytologically confirmed diagnosis of NSCLC with KRAS G12C mutation, candidacy to receive treatment with docetaxel, evidence of RECIST 1.1-defined disease progression on docetaxel per BICR, and an ECOG performance status of 0 to 2. Patients were excluded from the study if they have received previous treatment with an agent targeting KRAS G12C or had active brain metastases.
The primary end point of the study is PFS as assessed by BICR. Secondary end points included overall survival, ORR, duration of response, and safety.
