Alexander I. Spira, MD, PhD, FACP, Provides an Overview of the Use of Adagrasib in Advanced KRAS G12C–Mutant NSCLC at ASCO 2022


Alexander I. Spira, MD, PhD, FACP, details the safety profile of single-agent adagrasib in patients with KRAS G12C–mutated advanced or metastatic non–small cell lung cancer, as well as plans for future research following the phase 1/2 KRYSTAL-1 study.

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, discusses the safety profile of adagrasib (MRTX849) in patients with advanced/metastatic KRAS G12C–mutated non–small cell lung cancer from the phase 1/2 KRYSTAL-1 trial (NCT03785249). Moreover, Spira highlighted future analyses and research that are underway to further evaluated adagrasib within this patient population.


The rationale for the KRYSTAL-1 trial [was we took adagrasib]— a dedicated KRAS G12C inhibitor— to study [the agent] in the second-line setting. These were patients who got chemotherapy and immunotherapy, and they were treated with single agents adagrasib at 600 mg twice a day. We saw no new safety signals, [and although] a lot of patients did require dose reduction, only 7% of patients had to discontinue. With dose reductions, most patients were able to stay on treatment and tolerate it, which is the most important factor.

There will be some planned analyses looking at more subgroups, and new data cuts, which will be important. [We’ll also be] looking at some more of the co-mutations that come out over time, in terms of survival. Then, there’s going to be some newer studies. As mentioned [at the conference], there is the frontline study in combination with pembrolizumab [Keytruda] generating a lot of excitement. There’s also a confirmatory second-line study vs docetaxel.


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

Related Videos
Patients with KRAS G12C-mutated non–small cell lung cancer who have brain metastases or intolerability of intravenous infusion may be more suitable to receive a small molecule inhibitor compared with chemotherapy, says Sandip P. Patel, MD.
Treatment with sotorasib or adagrasib appears to be more tolerable among patients with KRAS G12C-mutated non–small cell lung cancer compared with docetaxel, according to Sandip Patel, MD.
Notions of blame around smoking may be a prominent factor in patients with lung cancer feeling stigmatized for developing their disease, according to Lisa Carter-Bawa PhD, MPH, APRN, ANP-C, FAAN.
Related Content