Trial finds that adagrasib demonstrates durable clinical activity in patients with KRAS-G12C mutations

The oral, selective KRAS G12C inhibitor KRAS-G12C inhibitor adagrasib demonstrated sturdy medical exercise, with a median total survival of 14.1 months and roughly one in three sufferers alive at two years, in keeping with analysis introduced at this time on the Worldwide Affiliation for the Examine of Lung Most cancers (IASLC) 2023 World Conference on Lung Most cancers in Singapore.

KRAS-G12C mutations happen in roughly 14% of sufferers with NSCLC. The KRYSTAL-1 research, a multi-cohort Section 1/2 trial, evaluated adagrasib as a monotherapy or together for sufferers with KRAS-G12C-mutated strong tumors. The U.S. Meals and Drug Administration (FDA) already granted accelerated approval of adagrasib for sufferers with beforehand handled KRAS-G12C-mutated superior/metastatic NSCLC primarily based on knowledge from this research. Moreover, the European Medicines Company (EMA) and the Medicines and Healthcare Merchandise Regulatory Company (MHRA) are presently reviewing the drug.

Within the two-year follow-up, pooled evaluation of the Section 1/1b Cohort and Section 2 Cohort A, 132 sufferers with KRAS-G12C-mutated NSCLC had been handled with adagrasib 600 mg orally twice day by day. The median age of sufferers was 64 years, with 56.8% being feminine. At baseline, 19.7% of sufferers had central nervous system metastases. Sufferers had acquired a median of two prior therapies, together with platinum-based and checkpoint inhibitor therapies.

In line with Shirish Gadgeel, MD from Henry Ford Most cancers Institute, Henry Ford Well being System, in Detroit, Mich., the outcomes confirmed a good goal response price (ORR) of 43.0%, with a median period of response (DOR) of 12.4 months. The median progression-free survival (PFS) was 6.9 months, and the median overall survival (OS) was 14.1 months. Notably, 52.8% of sufferers had been nonetheless alive at one yr, and roughly one in three sufferers (31.3%) remained alive at two years. The findings recommend sturdy medical exercise of adagrasib for KRAS-G12C-mutated NSCLC.

“The research knowledge demonstrates promising outcomes, offering hope for sufferers with this particular mutation,” Dr. Gadgeel stated. “Exploratory analyses indicated that the presence of co-mutations, reminiscent of KEAP1, STK11, or TP53, might influence the medical good thing about adagrasib and warrant additional investigation.”

Dr. Gadgeel reported that treatment-related antagonistic occasions had been manageable, with grade ≥3 TRAEs occurring in 40.9% of sufferers. Solely 2.3% of sufferers skilled grade 5 TRAEs, together with pneumonitis, cardiac failure, and pulmonary hemorrhage.

The continued Section 3 trial evaluating adagrasib monotherapy in contrast with docetaxel in beforehand handled superior KRAS-G12C-mutated NSCLC holds nice promise and will additional set up adagrasib as an important therapy choice for patients with this particular mutation, he reported.

Offered by
Worldwide Affiliation for the Examine of Lung Most cancers