Phase III CANDOR study of Darzalex + Kyprolis + dexamethasone shows improved PFS in multiple myeloma.- Janssen Biotech

The Janssen Pharmaceutical Companies of Johnson & Johnson announced results from the Phase III CANDOR study showing the addition of Darzalex (daratumumab) to Kyprolis (carfilzomib) and dexamethasone (DKd), compared to carfilzomib and dexamethasone (Kd) alone, significantly improved progression-free survival (PFS) in patients with relapsed/refractory multiple myeloma, resulting in a 37 percent reduction in the risk of progression or death (HR, 0.63; 95 percent CI, 0.46�0.85; P=0.0014). Results from the CANDOR study showed that, compared to Kd alone, DKd resulted in significantly longer PFS rates and response rates.

The primary endpoint of PFS was met after a median follow-up of 16.9 months and 16.3 months for the DKd and Kd arms, respectively. Median PFS was not reached in the DKd arm versus 15.8 months in the Kd arm. At 12 months, patients in the DKd arm had a 10 times higher rate of minimal residual disease (MRD)-negativity compared to patients treated with Kd alone (12.5 percent vs. 1.3 percent; P<0.0001). overall response rate orr was 84 percent in the dkd arm compared to 75 percent in the kd arm p="0.0040)." the rate of complete response cr or better was 29 percent dkd and 10 percent kd. median treatment duration was longer in the dkd arm than in the kd arm 17.5 vs. 10.1 months respectively.>

Median overall survival (OS) was not reached in either arm at a median follow-up time of 17 months (HR, 0.75; 95 percent CI, 0.49�1.13; P=0.08). In general, the safety profile of DKd was consistent with the known safety profiles of daratumumab and Kd, with the exception of treatment emergent fatal adverse events which were higher in the DKd arm compared to the Kd arm. The incidence of Grade 3 and above adverse events (AEs) was 82 percent and 74 percent of patients in DKd and Kd, respectively, while serious AEs (SAEs) occurred in 56 percent and 46 percent of patients, respectively. The frequency of Grade 3 and above cardiac failure was 4 percent (DKd) and 9 percent (Kd); rate of cardiac failure event leading to discontinuation of carfilzomib was similar in both arms at 4 percent (DKd) and 5 percent (Kd). The rate of treatment discontinuation due to AEs was similar in both arms (DKd, 22 percent vs. Kd 25 percent). Five deaths were reported as treatment-related in the DKd arm (pneumonia, sepsis, septic shock, acinetobacter infection and cardio-respiratory arrest, n=1 each). The study results were reported for the first time and presented as a Late-Breaking Abstract at the 2019 American Society of Hematology (ASH) Annual Meeting.