Neoplasms

November 6, 2017

Stemline Therapeutics announced that the pivotal phase II trial of SL-401 in blastic plasmacytoid dendritic cell neoplasm (BPDCN) has met its primary endpoint. The multicenter prospective study enrolled 45 BPDCN (32 first-line, 13 relapsed/refractory) patients at seven sites in the U.S. The trial consisted of three stages: stage one (lead-in, dose escalation), stage two (expansion) and stage three (pivotal, confirmatory). Across all stages, lines and doses in the trial (n=45 BPDCN patients; 32 first-line, 13 relapsed/refractory), the CR rate was 60% (27/45) and the ORR was 82% (37/45). In first-line patients who received SL-401 at all tested doses (n=32 patients), the CR rate was 69% (22/32) and the ORR was 88% (28/32). 41% (13/32) of first-line patients who received SL-401 at all tested doses have been bridged to SCT following remission on SL-401. The most common treatment-related adverse events (TRAEs) with SL-401 across BPDCN and other clinical trials (acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN) and multiple myeloma) (n=148 patients) were hypoalbuminemia (47%), aspartate aminotransferase increase (46%), alanine aminotransferase increase (45%), nausea (28%) and thrombocytopenia (28%). Capillary leak syndrome, a well-documented side effect, occurred in 19% of patients, of which 2% (3/148) were grade five, as previously reported. Based on feedback from the FDA, Stemline remains on track to begin submission of its Biologics License Application in the 4Q17-1Q18 timeframe. SL-401 has been granted Breakthrough Therapy Designation by the FDA for the treatment of BPDCN, and Orphan Drug Designation by the FDA and EU for the treatment of patients with BPDCN and acute myeloid leukemia.

December 21, 2015

Incyte has issued results of two phase III studies evaluating Jakafi (ruxolitinib) in patients with Myeloproliferative Neoplasms (MPNs). Data from a five-year follow-up of the COMFORT-II trial, a randomized, open-label study that 53% of patients treated with ruxolitinib (n=78/146) achieved at least a 35% reduction in spleen volume from baseline while on treatment during the study. Additionally, one-third of evaluable JAK2 V617F-positive patients had more than a 20% reduction in allele burden at 3.2 years (38%) and 3.7 years (31%). Patients treated with ruxolitinib also experienced improvements in bone marrow fibrosis (15.8%), with 32.2% reporting stable fibrosis scores. Overall, 59 (40%) and 35 (48%) deaths were reported in the ruxolitinib and best available therapy (BAT) arms, respectively. Median overall survival (OS) was not reached in the ruxolitinib arm and was 4.1 years in the group of patients originally receiving BAT. There was a 33% reduction in risk of death with ruxolitinib (HR, 0.67; 95% CI, 0.44-1.02; P=.06). The estimated probability of survival at five years was 56% with ruxolitinib and 44% with patients originally receiving BAT. The RESPONSE trial was an open-label study evaluating ruxolitinib in patients with polycythemia vera (PV) compared to those with BAT, who had an inadequate response to or had unacceptable side effects from hydroxyurea (HU). The analysis shows that patients who received ruxolitinib had greater mean reductions in white blood cell (WBC) counts compared with BAT or the HU subgroup of the BAT arm, and those reductions were maintained over time. In patients with baseline WBC counts ≥11×109/L, worsening WBC counts were observed in 10.8% of patients in the ruxolitinib arm v. 35.4% in the BAT arm (P=0.0002) and 47.8% in the HU subgroup (P<0.0001). In this same subgroup of patients with elevated WBC counts at baseline, a greater proportion of patients in the ruxolitinib arm (45%) normalized their WBC counts (achieving a WBC ≤10×109/L or a ≥50% reduction from baseline) compared with BAT (22%) or HU (9%) at week 32. The median time to achieve that response with ruxolitinib therapy was eight weeks. 

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