| General information |
| Database: | DB00007 |
| Objective: | In patients with melanoma, ipilimumab prolongs overall survival, and nivolumab produced durable tumor regression in a phase 1 trial. On the basis of their distinct immunologic mechanisms of action and supportive preclinical data, they conducted a phase 1 trial of nivolumab combined with ipilimumab in patients with advanced melanoma |
| Authors: | Wolchok JD, et al |
| Title: | Nivolumab plus ipilimumab in advanced melanoma. |
| Journal: | N Engl J Med. |
| Year: | 2013 |
| PMID: | 23724867 |
| Trial Design |
| Clinical Trial Id: | NCT01024231 |
| Agent: | ipilimumab
|
| Target: | Cytotoxic Tlymphocyte antigen 4 (CTLA4)
|
| Cancer Type: | melanoma |
| Cancer Subtype: | advanced melanoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 9 |
| Therapeutic Combination Content: | ipilimumab+nivolumab |
| Study Type: | a phase I trial |
| Key Patients Feature: | pts with advanced melanoma |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | They administered intravenous doses of nivolumab and ipilimumab in patients every 3 weeks for 4 doses, followed by nivolumab alone every 3 weeks for 4 doses (concurrent regimen). The combined treatment was subsequently administered every 12 weeks for up to 8 doses. In a sequenced regimen, patients previously treated with ipilimumab received nivolumab every 2 weeks for up to 48 doses. |
| Primary End Point: | safety and efficacy of combined therapy |
| Secondary End Point: | NA |
| Patients Number: | 86 |
| Trial Results |
| DLT_MTD: | not mentioned |
| Objective Response Rate: | The objectiveresponse rate (according to modified World Health Organization criteria) for all patients in the concurrentregimen group was 40%. Evidence of clinical activity (conventional, unconfirmed, or immunerelated response or stable disease for more than and equal to 24 weeks) was observed in 65% of patients. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | At the maximum doses that were associated with an acceptable level of adverse events (nivolumab at a dose of 1 mg per kilogram of body weight and ipilimumab at a dose of 3 mg per kilogram), 53% of patients had an objective response, all with tumor reduction of 80% or more. Grade 3 or 4 adverse events related to therapy occurred in 53% of patients in the concurrentregimen group but were qualitatively similar to previous experience with monotherapy and were generally reversible. Among patients in the sequencedregimen group, 18% had grade 3 or 4 adverse events related to therapy and the objectiveresponse rate was 20%. |
| Conclusions: | Concurrent therapy with nivolumab and ipilimumab had a manageable safety profile and provided clinical activity that appears to be distinct from that in published data on monotherapy, with rapid and deep tumor regression in a substantial proportion of patients. |