Bristol-Myers Squibb ( BMS ) has announced that a randomized blinded comparative phase 3 study evaluating Nivolumab versus Dacarbazine ( DTIC ) in patients with previously untreated BRAF wild-type advanced melanoma was stopped early because an analysis conducted by the independent Data Monitoring Committee ( DMC ) has shown evidence of superior overall survival in patients receiving Nivolumab compared to the control arm. Patients in the trial will be unblinded and allowed to cross over to Nivolumab.
CheckMate -066 investigators have been informed of the decision to stop the blinded comparative portion of the trial. The study, which was designed in consultation with the Committee for Medicinal Products for Human Use ( CHMP ), was primarily conducted in countries where DTIC is a commonly-used treatment in the first-line setting, including Canada, but not at U.S. trial sites.
CheckMate -066 is a phase 3 randomized, double-blind study of patients with previously untreated BRAF wild-type unresectable stage III and IV melanoma. The trial enrolled 418 patients who were randomized to receive either Nivolumab 3 mg/kg every two weeks or DTIC 1000 mg/m2 every three weeks.
The primary endpoint was overall survival. Secondary endpoints included progression free survival and objective response rate.
Cancer cells may exploit regulatory pathways, such as checkpoint pathways, to hide from the immune system and shield the tumor from immune attack. 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.
Researchers are investigating whether by blocking this pathway, Nivolumab would enable the immune system to resume its ability to recognize, attack and destroy cancer cells.
Global development program to study Nivolumab in multiple tumor types consists of more than 35 trials, as monotherapy or in combination with other therapies, in which more than 7,000 patients have been enrolled worldwide.
Among these are several potentially registrational trials in non-small cell lung carcinoma, melanoma, renal cell carcinoma ( RCC ), head and neck cancer, glioblastoma and non-Hodgkin lymphoma.
In 2013, the FDA granted Fast Track designation for Nivolumab in non-small cell lung cancer, melanoma and renal cell carcinoma.
In May 2014, the FDA granted Nivolumab Breakthrough Therapy Designation for the treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant and Brentuximab.
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 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: BMS, 2014