Merck announced that KEYTRUDA, Merck’s anti-PD-1 therapy, showed improvements in overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) as monotherapy for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC) whose tumors expressed PD-L1 (tumor proportion score [TPS] =1%), regardless of KRAS mutational status. These findings, which are based on an exploratory analysis of the pivotal Phase 3 KEYNOTE-042 trial, were presented in a proffered paper presentation (Abstract #LBA4) at the European Society for Medical Oncology (ESMO) Immuno-Oncology Congress 2019 in Geneva, Switzerland. The objective of the exploratory analysis was to assess the prevalence of KRAS mutations and their association with efficacy in the KEYNOTE-042 trial. Of the 1,274 untreated patients with metastatic nonsquamous NSCLC whose tumors expressed PD-L1 (TPS =1%) enrolled in KEYNOTE-042, 301 patients had KRAS evaluable data (n=232 without any KRAS mutation; n=69 with any KRAS mutation, including n=29 with the KRAS G12C mutation). Tissue tumor mutational burden (tTMB) and KRAS mutational status were determined by whole-exome sequencing (WES) of tumor tissue and matched normal DNA (blood).Patients were randomized 1:1 to receive KEYTRUDA 200 mg intravenously every three weeks (Q3W) (n=637) or investigator’s choice of chemotherapy (pemetrexed or paclitaxel) (n=637). Treatment continued until progression of disease or unacceptable toxicity. The primary endpoint was OS with a TPS of =50%, =20% and =1%, which were assessed sequentially. The secondary endpoints were PFS and ORR. Findings from this exploratory analysis showed that KEYTRUDA monotherapy was associated with improved clinical outcomes, regardless of KRAS mutational status, in patients with metastatic nonsquamous NSCLC versus chemotherapy. In this analysis, KEYTRUDA reduced the risk of death by 58% (HR=0.42 [95% CI, 0.22-0.81]) in patients with any KRAS mutation and by 72% (HR=0.28 [95% CI, 0.09-0.86]) in patients with the KRAS G12C mutation compared to chemotherapy. The safety profile of KEYTRUDA was consistent with what has been seen in previously reported studies among patients with metastatic NSCLC. Data from an exploratory analysis of KEYNOTE-189 (Abstract #LBA5), which evaluated KRAS mutations and their association with efficacy outcomes for KEYTRUDA in combination with pemetrexed and platinum chemotherapy, were also presented in a mini-oral session at the ESMO Immuno-Oncology Congress 2019. KEYNOTE-189 was conducted in collaboration with Eli Lilly and Company, the makers of pemetrexed (ALIMTA®).