The results from CheckMate -037, a phase 3 randomized, controlled open-label study of Nivolumab ( Opdivo ), an investigational PD-1 immune checkpoint inhibitor, versus investigator’s choice chemotherapy ( ICC ) in patients with advanced melanoma who were previously treated with Ipilimumab ( Yervoy ) were presented during ESMO 2014 Congress.
Based on a planned interim analysis of the co-primary endpoint, the objective response rate ( ORR ) was 32% ( 95% CI = 24, 41 ) in the Nivolumab arm ( n=120 ) and 11% ( 95% CI = 4, 23 ) in the ICC reference arm ( n=47 ) in patients with at least six months of follow up.
The majority ( 95% ) of responses were ongoing in the Nivolumab arm and the median duration of response was not reached. ORR was based on RECIST criteria as evaluated by an independent radiologic review committee ( IRRC ).
Safety was reported on all patients treated in the Nivolumab ( n=268 ) and ICC ( n=102 ) arms. The majority of Nivolumab treatment-related adverse events were grade 1/2 and managed using recommended treatment algorithms. Grade 3/4 drug-related adverse reactions were less frequent for the Nivolumab arm ( 9% versus 31% of patients treated chemotherapy ).
Serious grade 3/4 drug-related adverse reactions were reported in 5% and 9% of patients treated with Nivolumab and ICC, respectively. There was no grade 3/4 pneumonitis with Nivolumab.
Discontinuations due to drug-related adverse reactions, of any grade, occurred in 2% of Nivolumab-treated patients and 8% of patients administered ICC.
There were no deaths related to study drug toxicity.
Nivolumab is an investigational, fully-human PD-1 immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 ( programmed death-1 ) expressed on activated T-cells.
CheckMate -037 is a phase 3 randomized, open-label study ( n=370 ) designed to estimate the ORR in the Nivolumab arm and compare the overall survival of patients treated with Nivolumab versus those patients administered ICC.
Patients in the trial were randomized 2:1 to receive Nivolumab 3 mg/kg by intravenous infusion every two weeks ( n=268 ) or ICC ( Dacarbazine 1000 mg/m2 every three weeks or Carboplatin [ AUC ] 6 plus Paclitaxel 175 mg/m2 every three weeks; n=102 ) until progression or unacceptable toxicity.
Patients were classified by PD-1 ligand expression, BRAF status ( wild type or mutated ) and best response to prior treatment with Yervoy.
Co-primary endpoints of the study are ORR and overall survival.
Response, as measured by standard RECIST 1.1 criteria by an IRRC, was assessed 9 weeks after randomization, every 6 weeks for the first 12 months and then every 12 weeks. ( Xagena )
Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells ( melanocytes ) located in the skin. Metastatic melanoma is the deadliest form of the disease, and occurs when cancer spreads beyond the surface of the skin to the other organs, such as the lymph nodes, lungs, brain or other areas of the body.
The incidence of melanoma has been increasing for at least 30 years.
In 2012, an estimated 232,130 melanoma cases were diagnosed globally.
Melanoma is mostly curable when treated in its early stages. However, in its late stages, the average survival rate has historically been just six months with a one-year mortality rate of 75%, making it one of the most aggressive forms of cancer. ( Xagena )
Source: Bristol-Myers Squibb ( BMS ), 2014