Updated results from the phase 2 KRYSTAL-7 study continue to highlight the potential of first-line adagrasib (Krazati; Bristol Myers Squibb) combined with pembrolizumab (Keytruda; Merck) in patients with advanced or metastatic KRAS G12C–mutated non–small cell lung cancer (NSCLC) and programmed death-ligand 1 (PD-L1) tumor proportion score of ≥50%.1
The findings, which were presented at the European Lung Cancer Congress by Marina C. Garassino, MD, MBBS, of The University of Chicago, in Illinois, and colleagues, build upon initial reports and reinforce the efficacy and safety profile of this novel combination therapy.1
Patients enrolled in the study had advanced or metastatic KRAS G12C–mutated NSCLC with a known PD-L1 tumor proportion score of ≥50%. Adagrasib was administered at 400 mg orally twice daily, while pembrolizumab was given intravenously at 200 mg every 3 weeks.
The study’s primary endpoint was the investigator-assessed objective response rate (ORR) based on RECIST v1.1 criteria. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.
As of August 23, 2024, the data cutoff date, 149 patients had received the combination regimen. Among the 54 patients with PD-L1 ≥50%, the updated efficacy data showed:
These findings suggest that combination provides a durable clinical benefit in this patient population, with a promising ORR and prolonged PFS and OS.
The safety analysis indicated that treatment-related adverse events (TRAEs) were common but generally manageable, with any-grade TRAEs at 94.6%; grade 3/4 TRAEs at 68.4%; and grade 5 TRAEs reported in 3 patients (2 cases of pneumonia, 1 case of pneumonitis).
As research progresses, these findings could potentially reshape first-line treatment options for patients with KRAS G12C–mutated NSCLC, offering new hope for improved outcomes in this difficult-to-treat population.
Reference
- Garassino MC, Theelen WSME, Jänne PA, et al. First-line adagrasib (ADA) with pembrolizumab (PEMBRO) in patients with advanced/metastatic KRASG12C-mutated non-small cell lung cancer (NSCLC) and PD-L1 ≥ 50% from the phase 2 portion of KRYSTAL-7. Presented at: 2025 European Lung Cancer Congress. March 26-29, 2025; Paris, France. Abstract 5MO.