| General information |
| Database: | DB00002 |
| Objective: | Patients with melanoma that progresses on ipilimumab and, if BRAF(V600) mutantpositive, a BRAF or MEK inhibitor or both, have few treatment options. They assessed the efficacy and safety of two pembrolizumab doses versus investigatorchoice chemotherapy in patients with ipilimumabrefractory melanoma. |
| Authors: | Ribas A, et al |
| Title: | Pembrolizumab versus investigatorchoice chemotherapy for ipilimumabrefractory melanoma (KEYNOTE002): a randomised, controlled, phase 2 trial. |
| Journal: | Lancet Oncol. |
| Year: | 2015 |
| PMID: | 26115796 |
| Trial Design |
| Clinical Trial Id: | NCT01704287 |
| Agent: | pembrolizumab
|
| Target: | The antiprogrammeddeathreceptor1
|
| Cancer Type: | melanoma |
| Cancer Subtype: | advanced melanoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | an international, randomised, controlled, phase II clinical trial |
| Key Patients Feature: | patients aged 18 years or older from 73 hospitals, clinics, and academic medical centres in 12 countries who had confirmed progressive disease within 24 weeks after two or more ipilimumab doses and, if BRAF(V600) mutantpositive, previous treatment with a BRAF or MEK inhibitor or both. |
| Biomarker: | BRAFmutant |
| Biomark Analysis: | NA |
| Control Group Info: | investigatorchoice chemotherapy |
| Treatment Info: | randomly assigned (1:1:1) patients in a block size of six to receive intravenous pembrolizumab 2 mg/kg or 10 mg/kg every 3 weeks or investigatorchoice chemotherapy (paclitaxel plus carboplatin, paclitaxel, carboplatin, dacarbazine, or oral temozolomide). Randomisation was stratified by ECOG performance status, lactate dehydrogenase concentration, and BRAF(V600) mutation status. |
| Primary End Point: | the prespecified second interim analysis of progression free survival in the intentiontotreat population. |
| Secondary End Point: | NA |
| Patients Number: | 540 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | PFS was improved in patients assigned to pembrolizumab 2 mg/kg (HR 0.57, 95% CI 0.450.73; p<0.0001) and those assigned to pembrolizumab 10 mg/kg (0.50, 0.390.64; p<0.0001) compared with those assigned to chemotherapy. 6month progression free survival was 34% (95% CI 2741) in the pembrolizumab 2 mg/kg group, 38% (3145) in the 10 mg/kg group, and 16% (1022) in the chemotherapy group. |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Treatmentrelated grade 34 adverse events occurred in 20 (11%) patients in the pembrolizumab 2 mg/kg group, 25 (14%) in the pembrolizumab 10 mg/kg group, and 45 (26%) in the chemotherapy group. The most common treatmentrelated grade 34 adverse event in the pembrolizumab groups was fatigue (two [1%] of 178 patients in the 2 mg/kg group and one [<1%] of 179 patients in the 10 mg/kg group, compared with eight [5%] of 171 in the chemotherapy group). Other treatmentrelated grade 34 adverse events include generalised oedema and myalgia (each in two [1%] patients) in those given pembrolizumab 2 mg/kg; hypopituitarism, colitis, diarrhoea, decreased appetite, hyponatremia, and pneumonitis (each in two [1%]) in those given pembrolizumab 10 mg/kg; and anaemia (nine [5%]), fatigue (eight [5%]), neutropenia (six [4%]), and leucopenia (six [4%]) in those assigned to chemotherapy. |
| Conclusions: | These findings establish pembrolizumab as a new standard of care for the treatment of ipilimumabrefractory melanoma. |