Phase II study results of KRASG12c inhibitor adagrasib in patients with NSCLC

November 2022 Cancer trials Nalinee Pandey

The findings of the phase II KRYSTAL-1 study demonstrate the efficacy of the KRASG12c inhibitor adagrasib in patients with non-small cell lung cancer (NSCLC). The results of the clinical study were recently published in the New England Journal of Medicine.

KRASG12c is the most prevalent driver mutation observed in NSCLC patients. Few allele-specific inhibitors have been developed and tested for efficacy and safety  Adagrasib is a selective inhibitor of KRASG12c, whose safety and effectiveness have been demonstrated in the phase Ib KRYSTAL-1 study. Its efficacy and safety were further evaluated in the phase II KRYSTAL-1 study.

Phase II KRYSTAL-1

The phase II KRYSTAL-1 study enrolled 116 NSCLC patients with a KRASG12c mutation that were previously treated with chemotherapy and immunotherapy.  The participants were administered adagrasib, 600 mg, twice daily. The study’s primary endpoint was the objective response rate (ORR) and the secondary endpoints included duration of response, progression-free survival (PFS) and overall survival.

Tumour shrinkage

As of October 15, 2021, 112 patients were evaluable, with an ORR of 42.9%. The median PFS upon adagrasib treatment was 6.5 months. Importantly, tumour shrinkage was seen in the majority (79.5%) of patients. Notably, in the group of patients (n=33) previously treated for brain metastasis, the intracranial ORR was 33.3%. Most (97.4%) patients experienced treatment-related adverse events (TRAEs). Grade 3 TRAEs were seen in 44.8% of patients leading to two grade 5 events and treatment discontinuation in 6.9% of patients.

Conclusion

In conclusion, adagrasib appeared to be clinically effective and no new safety signals were observed as a result of treatment with adagrasib in NSCLC patients with KRASG12c mutations.

Reference

Jänne PA, Riely GJ, Gadgeel SM, et al. Adagrasib in Non-Small-Cell Lung Cancer Harboring a KRASG12C Mutation. N Engl J Med 2022;387:120-31.

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