Adenocarcinoma

October 17, 2016

Merrimack Pharmaceuticals reported results of a phase III study of Onivyde (irinotecan liposome injection) in combination with fluorouracil (5-FU) and leucovorin for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) following treatment with gemcitabine-based therapy. The overall survival advantage of Onivyde in combination with 5-FU and leucovorin versus 5-FU and leucovorin alone was maintained in this extended analysis: 6.2 months versus 4.2 months (p=0.039, hazard ratio (HR) =0.75, 95% CI: [0.057- 0.99]). The probability of survival at one year was greater in the Onivyde combination arm of the study when compared to the 5-FU and leucovorin arm: 12-month overall survival estimates of 26% (95% CI, 18-35%) were observed in the Onivyde combination treatment arm compared to 16% (95% CI, 10-24%) for 5-FU and leucovorin arm. The overall response rate (ORR) for the Onivyde plus 5-FU and leucovorin arm was 16% versus 1% for the 5-FU and leucovorin arm (p<0.0001). Treatment with Onivyde in combination with 5-FU and leucovorin provided a two-fold improvement in disease control rate compared with 5-FU and leucovorin alone (52% v. 24%, respectively). Final results suggest that patients treated with Onivyde in combination with 5-FU and leucovorin had no notable deterioration in quality of life at 12 weeks despite the addition of a second chemotherapeutic agent to 5-FU and leucovorin. No new safety concerns were noted and the overall safety profile was manageable with the most common grade three adverse events of neutropenia, diarrhea, fatigue, vomiting and asthenia.

January 25, 2016

Merrimack Pharmaceuticals issued results of a phase III study of ONIVYDE (irinotecan liposome injection) in combination with fluorouracil (5-FU) and leucovorin achieved a substantial improvement in 12-month overall survival in patients with post-gemcitabine metastatic pancreatic adenocarcinoma when compared to 5-FU and leucovorin alone. The randomized, open label study in patients with metastatic adenocarcinoma of the pancreas who received prior gemcitabine-based therapy was the largest phase III study in this setting to date. A total of 417 patients were randomized across the three arms. Primary survival analysis was based on 313 events and showed that ONIVYDE in combination with 5-FU and leucovorin significantly improved overall survival v. 5-FU and leucovorin alone: 6.1 months v. 4.2 months (p=0.012, unstratified hazard ratio (HR) =0.67, 95% CI: [0.49-0.92]). The monotherapy regimen in this study did not show improvement over the 5-FU and leucovorin arm: 4.9 v. 4.2 months (p=0.94, HR=0.99, 95% CI: [0.77-1.28]). No new safety or tolerability concerns were note in the updated analysis. The primary NAPOLI-1 study results were the basis of the recent FDA and Taiwan FDA approval of ONIVYDE in combination with 5-FU and leucovorin for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy. Merrimack and Baxalta have entered into an exclusive licensing agreement for the development and commercialization of ONIVYDE outside of the U.S. and Taiwan. Baxalta’s marketing authorization application for the treatment of patients with metastatic adenocarcinoma of the pancreas who have been previously treated with gemcitabine-based therapy is currently under review with the EMA.

December 7, 2015

Merrimack and Baxalta have reported results of a global, randomized, open-label phase III trial of Onivyde, in combination with 5-FU and leucovorin, for treatment of metastatic adenocarcinoma of the pancreas. Patients were enrolled at 76 sites in North America, South America, Europe, Asia and Oceania. A total of 417 patients were randomized across the three arms. The Onivyde combination regimen demonstrated a significant increase in median overall survival v. 5-FU and leucovorin alone: 6.1 months v. 4.2 months (p=0.012, unstratified hazard ratio for death (HR) =0.67, 95% CI: [0.490.92]). The monotherapy regimen in the study did not show improvement over the 5-FU and leucovorin arm: 4.9 v. 4.2 months (p=0.94, HR=0.99, 95% CI: [0.771.28]). Onivyde in combination with 5-FU and leucovorin achieved a longer progression- free survival compared with the 5-FU and leucovorin arm (3.1 months v. 1.5 months; unstratified HR=0.56 [95% CI, 0.410.75]). Unconfirmed objective response rate was higher in the Onivyde in combination with 5-FU and leucovorin arm than in the 5-FU and leucovorin arm: 16% (19/117) v. 1% (1/119) (difference 15.4 percentage points, 95% CI, 8.5-22.3; p<0.0001). The most common grade three or four adverse events that occurred more frequently in the Onivyde combination arm (>2% incidence v. 5-FU and leucovorin) were neutropenia, diarrhea, vomiting and fatigue. Study results were the basis of the recent FDA and Taiwan FDA approval. In May 2015, the EMA accepted for review Baxalta’s marketing authorization application for Onivyde based on the same clinical results.

February 11, 2013

Seattle Genetics released interim results for a phase I trial of ASG-5ME for the treatment of metastatic pancreatic ductal adenocarcinoma (PDA). This dose-ranging, placebo-controlled study enrolled 35 patients with metastatic PDA who were heavily pre-treated with a median of three prior therapies. Subjects received doses of ASG-5ME ranging from 0.3mg/kg to 1.5mg/kg weekly for three out of every four weeks, or placebo. Results showed that ASG-5ME 1.2mg/kg was the maximum tolerated dose. Of the patients receiving ASG-5ME 1.2mg/kg, one patient achieved a partial response, six patients achieved a stable disease and four patients had progressive disease. Seven patients were not evaluable for response. The drug was well tolerated. The most frequent adverse events were fatigue, vomiting, decreased appetite, abdominal pain and nausea. Based on these data, Seattle Genetics will continue the phase I trial.

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