| General information |
| Database: | DB00008 |
| Objective: | In a phase 1 doseescalation study, combined inhibition of Tcell checkpoint pathways by nivolumab and ipilimumab was associated with a high rate of objective response, including complete responses, among patients with advanced melanoma. |
| Authors: | Postow MA, et al |
| Title: | Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. |
| Journal: | N Engl J Med. |
| Year: | 2015 |
| PMID: | 25891304 |
| Trial Design |
| Clinical Trial Id: | NCT01927419 |
| Agent: | Nivolumab and ipilimumab
|
| Target: | NA
|
| Cancer Type: | melanoma |
| Cancer Subtype: | advanced melanoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 9 |
| Therapeutic Combination Content: | Nivolumab+ ipilimumab |
| Study Type: | a phase I doseescalation study |
| Key Patients Feature: | patients with metastatic melanoma who had not previously received treatment |
| Biomarker: | BRAF V600 |
| Biomark Analysis: | as in the conclusion |
| Control Group Info: | single arm |
| Treatment Info: | they randomly assigned patients in a 2:1 ratio to receive ipilimumab (3 mg per kilogram of body weight) combined with either nivolumab (1 mg per kilogram) or placebo once every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram) or placebo every 2 weeks until the occurrence of disease progression or unacceptable toxic effects |
| Primary End Point: | the rate of investigatorassessed, confirmed objective response among patients with BRAF V600 wildtype tumors. |
| Secondary End Point: | NA |
| Patients Number: | 142 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Among patients with BRAF wildtype tumors, the rate of confirmed objective response was 61% (44 of 72 patients) in the group that received both ipilimumab and nivolumab (combination group) versus 11% (4 of 37 patients) in the group that received ipilimumab and placebo (ipilimumabmonotherapy group) (P<0.001), with complete responses reported in 16 patients (22%) in the combination group and no patients in the ipilimumabmonotherapy group. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The median progression free survival was not reached with the combination therapy and was 4.4 months with ipilimumab monotherapy (hazard ratio associated with combination therapy as compared with ipilimumab monotherapy for disease progression or death, 0.40; 95% confidence interval, 0.23 to 0.68; P<0.001). Similar results for response rate and progression free survival were observed in 33 patients with BRAF mutationpositive tumors. |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Drugrelated adverse events of grade 3 or 4 were reported in 54% of the patients who received the combination therapy as compared with 24% of the patients who received ipilimumab monotherapy. Select adverse events with potential immunologic causes were consistent with those in a phase 1 study, and most of these events resolved with immunemodulating medication. |
| Conclusions: | The objectiveresponse rate and the progression free survival among patients with advanced melanoma who had not previously received treatment they were significantly greater with nivolumab combined with ipilimumab than with ipilimumab monotherapy. Combination therapy had an acceptable safety profile. |