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).
Transcript:
[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
References
- 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
- 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
These data support less restrictive clinical trial eligibility criteria for those with metastatic NSCLC. This is especially true regarding both targeted therapy and immunotherapy treatment regimens.
