Alexander I. Spira, MD, PhD, FACP, Highlights Findings From the Phase 1/2 KRYSTAL-1 Trial of Adagrasib in KRAS G12C–Mutant Advanced NSCLC


Treatment with adagrasib monotherapy yielded an overall response rate of 42.9% in patients with KRAS G12C–mutated advanced/metastatic non–small cell lung cancer, according to Alexander I. Spira, MD, PhD, FACP.

In an interview with CancerNetwork® during the 2022 American Society of Clinical Oncology Annual Meeting, Alexander I. Spira, MD, PhD, FACP, a medical oncologist and co-director of the Virginia Cancer Specialists Research Institution, and director of the Thoracic and Phase I Program and clinical assistant professor at Johns Hopkin, discussed key findings from the phase 1/2 KRYSTAL-1 trial (NCT03785249), assessing the safety and efficacy of adagrasib (MRTX849) monotherapy in patients with KRAS G12C–mutated advanced or metastatic non–small cell lung cancer.1

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


[One of] the key findings were that the [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 this is another one in the armamentarium. It’s important because the standard of care other than that is chemotherapy and second-line chemotherapy, usually docetaxel, is not super effective and pretty toxic. It opens up options for these patients in the second-line setting. It’s also proof of concept because KRAS mutations have been the undruggable target for a long time.

We also presented the beginning of some [central nervous system] CNS data in patients with stable treated metastases.2 Some of those patients did not have radiation, and there’s some efficacy there. We hope to see some more in a presentation by my colleague, Joshua K. Sabari, MD, who will hopefully present some more 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) harboring a KRASG12C mutation. J Clin Oncol. 2022;40(suppl 16):9002. doi:10.1200/JCO.2022.40.16_suppl.9002
  2. Sabari JK, Spira AI, Heist RS, et al. Activity of adagrasib (MRTX849) in patients with KRASG12C-mutated NSCLC and active, untreated CNS metastases in the KRYSTAL-1 trial. J Clin Oncol. 2022;40(suppl 17):9009. doi:10.1200/JCO.2022.40.17_suppl.LBA9009
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