Plummer R, Dean E, Arkenau HT, et al. - Findings demonstrate good tolerability of berzosertib plus gemcitabine in patients with advanced, pre-treated non–small cell lung cancer (NSCLC). Preliminary signs of clinical efficacy were observed. Future clinical trials should include genomically selected cases.

• Berzosertib (formerly M6620, VX-970) is an intravenous, highly potent and selective, first-in-class ataxia telangiectasia and Rad3-related protein kinase inhibitor.

• This study involved 38 adult patients with advanced histologically confirmed NSCLC, who were given berzosertib 210 mg/m ² (days 2 and 9) and gemcitabine 1,000 mg/m ² (days 1 and 8) at the recommended phase 2 dose established in the dose escalation part of the study.

• Fatigue (55.3%), anemia (52.6%), and nausea (39.5%) were the most common treatment–emergent adverse events.

• An objective response rate (ORR) of 10.5% was obtained; ORR was 30.0% and 11.0% in patients with high loss of heterozygosity (LOH) and in those with low LOH, respectively.

• In patients with high, intermediate, and low tumor mutational burden (TMB), the estimated ORR was 33.0%, 12.5%, and 0%, respectively.

• Overall, response rate was numerically elevated in cases with high TMB and LOH scores.

• Gemcitabine showed no apparent impact on the pharmacokinetics of berzosertib.