Median PFS of 3.5 months was observed in the nivolumab monotherapy group (31), with ORR of 28%. including patients with negative PD-L1 expression tumors, clinical trials are ongoing to assess the safety and efficacy of combination immune checkpoint inhibitors and combination immune checkpoint inhibitors with targeted therapy. Immune checkpoint inhibitors have been found to be a promising therapeutic drug class with NS 309 sustainable response rates and a tolerable safety profile, and efforts continue to improve these drugs in patients with NSCLC. 73% in the monotherapy group. However, 1-year OS was not reached in the group receiving nivolumab plus ipilimumab every 12 weeks (31). Confirmed objective response was observed in 18 patients (47%; 95% CI, 31C64%) in the ipilimumab every 12-week group compared to 15 patients (38%; 95% CI, 23C55%) in the ipilimumab every 6 weeks group with all responses only partial responses. The study did not observe any patient with a complete response (31). The median PFS and ORR in patients with 1% PD-L1 expression was 8.1 months and 57% with nivolumab plus ipilimumab every 12 weeks versus 10.6 months and 57% with nivolumab plus ipilimumab every 6 weeks (31). Median PFS of 3.5 months was observed in the nivolumab monotherapy group (31), with ORR of 28%. For patients with EGFR-mutant NSCLC, ORR was 50% in the combination arm versus 41% in those with EGFR wild-type NSCLC (31). The ORR was 14% in EGFR-mutated patients (n=7) 30% in EGFR wild-type NSCLC patients (n=30) receiving nivolumab monotherapy (31). As seen with other combination immunotherapy trials, all grade adverse events were similar across all study arms, with 82% in the 12-week combination, 72% in the 6-week combination, and 71% in the monotherapy groups (31). As expected, there was a higher incidence of grade 3/4 irAEs in the combination arms (37% for 12-week combination, 33% for 6-week combination) versus 19% in the monotherapy arm (31). No treatment-related deaths were observed; however, 12 patients (32%) in the ipilimumab every 12 week arm and 11 patients (28%) in the ipilimumab every 6 Rabbit Polyclonal to FXR2 weeks arm experienced serious adverse events (31). Overall, the study found that nivolumab plus ipilimumab in the first-line setting was tolerable and resulted in improved and sustainable response rates (31). A phase III clinical trial is ongoing to evaluate nivolumab alone and in combination with ipilimumab 1 mg/kg every 6 weeks or platinum-doublet chemotherapy in the front-line setting with OS as the primary endpoint and plans to enroll 1,980 patients (144TipCheckMate 227, “type”:”clinical-trial”,”attrs”:”text”:”NCT02477826″,”term_id”:”NCT02477826″NCT02477826) (32). Another combination trial that is on-going is the ARTIC NS 309 trial. This global phase III randomized, open-label multicenter clinical trial is assessing different treatment regimens, including durvalumab plus tremelimumab versus durvalumab monotherapy or tremelimumab monotherapy versus standard of care in patients with negative PD-L1 expression in NSCLC (“type”:”clinical-trial”,”attrs”:”text”:”NCT02352948″,”term_id”:”NCT02352948″NCT02352948) (33). The MYSTIC trial (“type”:”clinical-trial”,”attrs”:”text”:”NCT02453282″,”term_id”:”NCT02453282″NCT02453282) is an open-label, global, multicenter, randomized, phase III study, evaluating the safety and efficacy of durvalumab plus tremelimumab in stage IV NSCLC patients in the first-line setting (34). Patients were randomized 1:1:1 to receive durvalumab plus tremelimumab versus monotherapy durvalumab versus standard of care with platinum-based chemotherapy (34). Patients were stratified based on PD-L1 expression status and histology (34). A press release from AstraZeneca reported that the combination of durvalumab and tremelimumab did not meet the primary endpoint of improved PFS compared with standard of care with platinum-based chemotherapy, but the study remains on-going to evaluate OS (35). In the NEPTUNE trial (“type”:”clinical-trial”,”attrs”:”text”:”NCT02542293″,”term_id”:”NCT02542293″NCT02542293), a randomized phase III trial in patients with advanced or metastatic EGFR and ALK wild-type NSCLC, durvalumab plus tremelimumab was NS 309 compared versus.