| General information |
| Database: | DB00962 |
| Objective: | Nivolumab (a programmed death 1 [PD1] checkpoint inhibitor) and ipilimumab (a cytotoxic Tlymphocyteassociated antigen 4 [CTLA4] checkpoint inhibitor) have been shown to have complementary activity in metastatic melanoma. In this randomized, doubleblind, phase 3 study, nivolumab alone or nivolumab plus ipilimumab was compared with ipilimumab alone in patients with metastatic melanoma |
| Authors: | Larkin J, et al |
| Title: | Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. |
| Journal: | N Engl J Med. |
| Year: | 2015 |
| PMID: | 26027431 |
| Trial Design |
| Clinical Trial Id: | NCT01844505 |
| Agent: | Nivolumab and Ipilimumab
|
| Target: | NA
|
| Cancer Type: | melanoma |
| Cancer Subtype: | melanoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | Nivolumab+Ipilimumab |
| Study Type: | randomized, doubleblind, phase III study |
| Key Patients Feature: | previously untreated patients with unresectable stage III or IV melanoma |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | nivolumab alone versus nivolumab plus ipilimumab verus ipilimumab alone |
| Treatment Info: | they assigned, in a 1:1:1 ratio, pts to nivolumab alone, nivolumab plus ipilimumab, or ipilimumab alone |
| Primary End Point: | progression free survival and overall survival |
| Secondary End Point: | NA |
| Patients Number: | 945 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 43.7% (95% CI, 38.1 to 49.3) in the nivolumab group, 57.6% (95% CI, 52.0 to 63.2) in the nivolumabplusipilimumab group, and 19.0% (95% CI, 14.9 to 23.8) in the ipilimumab group |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 11.5 months (95% confidence interval [CI], 8.9 to 16.7) with nivolumab plus ipilimumab, as compared with 2.9 months (95% CI, 2.8 to 3.4) with ipilimumab (hazard ratio for death or disease progression, 0.42; 99.5% CI, 0.31 to 0.57; P<0.001), and 6.9 months (95% CI, 4.3 to 9.5) with nivolumab (hazard ratio for the comparison with ipilimumab, 0.57; 99.5% CI, 0.43 to 0.76; P<0.001). |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common adverse events in the nivolumabplusipilimumab group were diarrhea (in 44.1% of patients), fatigue (in 35.1%), and pruritus (in 33.2%). The incidence of treatmentrelated adverse events of grade 3 or 4 was also higher in the nivolumabplusipilimumab group (55.0%) than in the nivolumab group (16.3%) or the ipilimumab group (27.3%). |
| Conclusions: | Among previously untreated patients with metastatic melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression free survival than ipilimumab alone. In patients with PDL1negative tumors, the combination of PD1 and CTLA4 blockade was more effective than either agent alone. (Funded by BristolMyers Squibb; CheckMate 067 ClinicalTrials.gov number, NCT01844505.). |