On June 11, 2024, the Phase II study results of Garsorasib (D-1553) for KRAS G12C-mutant non-small cell lung cancer (NSCLC) were published in The Lancet Respiratory Medicine, one of the world’s most prestigious medical journals (Impact Factor: 76.2). This study, conducted in China, highlighted the promising efficacy and safety profile of Garsorasib, marking it as the first domestic KRAS G12C inhibitor to be featured in a Lancet journal.
Key Findings from the Phase II Study:
- Objective Response Rate (ORR): 50%
- Disease Control Rate (DCR): 89%
- Median Duration of Response (DOR): 12.8 months
- Median Progression-Free Survival (PFS): 7.6 months
- Median Overall Survival (OS): Not yet reached
The study was a multi-center, open-label, single-arm Phase II trial (NCT05383898) conducted in KRAS G12C-mutant NSCLC patients who had previously failed first-line treatment. The results indicate a high tumor response rate and durable disease control, reinforcing Garsorasib as a promising treatment option for patients with KRAS G12C mutations in NSCLC.
Study Design and Patient Population:
- The study enrolled 123 patients with KRAS G12C-mutant NSCLC, including 88% male patients with a median age of 64 years.
- The patients had previously received platinum-based chemotherapy and anti-PD-(L)1 therapy, and all had disease progression or intolerability to these treatments.
- Patients received 600 mg BID of Garsorasib in 21-day cycles.
The primary endpoint of the trial was the Objective Response Rate (ORR), which was assessed by an independent review committee (IRC). Secondary endpoints included Duration of Response (DOR), Progression-Free Survival (PFS), and Overall Survival (OS), as well as safety and pharmacokinetics.
Safety Profile:
- 95% of patients experienced treatment-related adverse events (TRAEs).
- The most common TRAEs (≥20%) were elevations in liver enzymes (AST, ALT, GGT), anemia, vomiting, and nausea.
- 50% of patients experienced Grade 3 or higher TRAEs.
- Despite these, the majority of adverse events were manageable, with no patients discontinuing treatment due to TRAEs.
- 37% of patients required dose reductions, and 42% experienced dose interruptions.
Expert Commentary:
An accompanying expert review highlighted that Garsorasib has the potential to offer a new oral targeted therapy for KRAS G12C-mutant NSCLC patients, who traditionally have limited treatment options and poor prognosis. The expert panel noted that if Garsorasib gains regulatory approval, it could provide KRAS G12C-mutant NSCLC patients worldwide with an important new treatment choice.
Clinical Implications:
The KRAS G12C mutation is found in a significant subset of NSCLC patients, and previously, this mutation was considered undruggable. Garsorasib represents a breakthrough therapy, selectively and irreversibly binding to the KRAS G12C mutant protein, rendering it inactive and blocking tumor growth. The published study confirms that Garsorasib has the potential to become a game-changer in treating KRAS G12C-mutant NSCLC, a population with an unmet clinical need.
Regulatory Status:
Garsorasib has already been accepted for priority review by the National Medical Products Administration (NMPA) in China for the treatment of locally advanced or metastatic NSCLC with KRAS G12C mutations, following first-line treatment failure.
The Phase II trial results in The Lancet Respiratory Medicine further validate the drug’s clinical profile, supporting its potential approval as a first-line targeted therapy for KRAS G12C-mutant cancers.
Conclusion:
This publication in The Lancet Respiratory Medicine underscores the clinical promise of Garsorasib for KRAS G12C-mutant NSCLC. The study’s findings show that Garsorasib provides significant tumor response, durable control, and a favorable safety profile, offering new hope to NSCLC patients with this difficult-to-treat genetic mutation.
As the drug advances through regulatory processes and additional clinical studies, it holds the potential to make a significant impact in lung cancer treatment globally.