Alexander I. Spira, MD, PhD, FACP, presents results from the KRYSTAL-1 Phase 1/2 trial of adagrasib in NSCLC KRAS G12C–Mutant Advanced

According to Alexander I. Spira, MD, PhD, FACP, treatment with adagrasib monotherapy resulted in an overall response rate of 42.9% in patients with advanced/metastatic non-small cell lung cancer with KRAS mutation G12C.

In an interview with CancerNetwork® during the American Society for Clinical Oncology 2022 Annual MeetingAlexander I. Spira, MD, PhD, FACP, medical oncologist and co-director of the Virginia Cancer Specialists Research Institution, and thoracic and phase I program director and clinical assistant professor at Johns Hopkin, discussed key Phase 1 results/ 2 KRYSTAL-1 trial (NCT03785249), evaluating the safety and efficacy of adagrasib (MRTX849) monotherapy in patients kras Advanced or metastatic non-small cell lung cancer with G12C mutation.1

The disease control rate was 80%% (95% CI, 70.8% to 865%), and the median duration of response was 8.5 months (95% CI, 6.2 to 13.8). Of the 112 patients included in the trial, 31 continued treatment. Additionally, the median overall survival was 12.6 months (95% CI, 9.2-19.2) and the median progression-free survival was 6.5 months (95% CI, 47-8.4 ).


[One of] the main conclusions were that [objective response rate] was 43% [95% CI, 33.5%-52.6%). That in of itself is a milestone because it’s a drug that targets KRAS G12C. Currently, there is an approved drug, sotorasib [Lumakras], so that’s another one in the arsenal. This is important because the standard of care other than this is chemotherapy, and second line chemotherapy, usually docetaxel, is not super effective and quite toxic. This opens up options for these patients as part of the second line. It is also a proof of concept because kras mutations have long been the unavoidable target.

We also presented the beginning of some [central nervous system] CNS data in patients with stable treated metastases.2 Some of these patients did not receive radiation, and there is some efficacy there. We hope to see more in a presentation by my colleague, Joshua K. Sabari, MD, who will hopefully present further CNS data in patients with untreated brain metastases.2


  1. Spira AI, Riely GJ, Gadgeel SM, et al. KRYSTAL-1: Activity and safety of adagrasib (MRTX849) in patients with advanced/metastatic non-small cell lung cancer (NSCLC) with a KRASG12C mutation. J Clin Oncol. 2022;40(supplement 16):9002. doi:10.1200/JCO.2022.40.16_suppl.9002
  2. Sabari JK, Spira AI, Heist RS, et al. Adadagrasib (MRTX849) activity in patients with KRASG12C-mutated NSCLC and active, untreated CNS metastases in the KRYSTAL-1 trial. J Clin Oncol. 2022;40(supplement 17):9009. doi:10.1200/JCO.2022.40.17_suppl.LBA9009

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