On October 27, 2015 Merrimack (Nasdaq: MACK) and Baxalta Incorporated (NYSE: BXLT) reported the enrollment of the first patient in an exploratory Phase 2 clinical study of ONIVYDE (irinotecan liposome injection), also known as MM-398 or "nal-IRI," in previously untreated, metastatic pancreatic adenocarcinoma (Press release, Merrimack, OCT 27, 2015, View Source [SID:1234507804]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Phase 2 clinical study of ONIVYDE in patients with previously untreated, metastatic pancreatic adenocarcinoma will assess the safety and efficacy of the combination of ONIVYDE plus fluorouracil (5-FU) and leucovorin (LV), with or without the addition of oxaliplatin, versus nab-paclitaxel and gemcitabine. The start-up of this study resulted in $62.5M of milestone payments to Merrimack from Baxalta.

"The initiation of this Phase 2 study is an important step in evaluating ONIVYDE’s effectiveness as a front-line treatment option for patients diagnosed with metastatic pancreatic cancer. This design allows us to quickly and efficiently learn about the safety and efficacy of these potential new regimens prior to entering into a large, confirmatory Phase 3 study," said Eliel Bayever, M.D., Vice President at Merrimack and medical director for ONIVYDE.

"Our team is extremely excited to be the first center in the world to open this trial of ONIVYDE in front-line metastatic pancreatic cancer given the results of the NAPOLI trial in the post-gemcitabine setting," said Dr. Andrew Dean, one of the principal investigators on the study and an Oncologist at St John of God Hospital Subiaco in Australia.

In addition to pancreatic cancer, there are ongoing Phase 1 studies of ONIVYDE in glioma, breast cancer, gastric cancer and pediatric solid tumors.

"This trial is part of our broad development plan for ONIVYDE in solid tumors that have high unmet medical need," said John Orloff, M.D., head of Research & Development and chief scientific officer, Baxalta. "By expanding our research of ONIVYDE into patients who have not been previously treated for metastatic pancreatic cancer, our hope is that we learn more about its potential to meet the needs of people who currently have few approved treatment options."

Merrimack and Baxalta have entered into an exclusive licensing agreement to develop and commercialize ONIVYDE outside of the United States.A Marketing Authorization Application is under review in the European Union for the treatment of adult patients with metastatic adenocarcinoma of the pancreas who have been previously treated with gemcitabine-based therapy. PharmaEngine, Inc. (Taipei, Taiwan) holds the rights to commercialize ONIVYDE in Taiwan.

Clinical Study of ONIVYDE in Previously Untreated, Metastatic Pancreatic Adenocarcinoma

The study will be conducted in two parts, first assessing the safety of ONIVYDE in combination with 5-FU/LV and oxaliplatin, and then expanding into a three arm randomized study assessing the safety and efficacy of the combination of ONIVYDE and 5-FU/LV with or without oxaliplatin versus nab-paclitaxel and gemcitabine. Eligible patients for the study must have received no prior systemic treatment.

In the first part of the study, approximately 6-18 patients will be enrolled. The primary outcome for Part 1 of the study is to evaluate the safety and tolerability of ONIVYDE in combination with 5-FU/LV and oxaliplatin. In the second part of the study, an additional 150 patients (50 patients per arm) with previously untreated, metastatic pancreatic adenocarcinoma will be enrolled and randomized to receive either ONIVYDE in combination with 5-FU/LV and oxaliplatin, ONIVYDE in combination with 5-FU/LV, or nab-paclitaxel and gemcitabine. In Part 2, efficacy of the ONIVYDE containing regimens will be compared to the nab-paclitaxel and gemcitabine regimen, evaluating progression free survival (PFS) rate at 24 weeks, as well as overall survival, PFS, objective response rate, tumor marker CA19-9 response, safety and tolerability.

Merrimack and Baxalta plan to conduct the study at sites in the United States, Canada, Europe, Australia, New Zealand, Taiwan and South Korea. The first patient in the study was dosed at St. John of God Subiaco Hospital in Subiaco, Western Australia. For more information, please visit www.clinicaltrials.gov (Identifier: NCT02551991). Based on the current design of this study, data are expected in the first half of 2017. Guidance will be updated as recruitment continues.

About Pancreatic Cancer

Pancreatic cancer is rare and deadly. It accounts for only 3% of all cancer cases1, but is the fourth leading cause of cancer-related death2, leading to a five year survival rate of only 7%3. Each year an estimated 49,000 new cases are diagnosed in the United States3, two-thirds of which are among people aged 65 or older4. There are an estimated 338,000 new cases diagnosed each year worldwide5.

The pancreas is composed of two main cell types: exocrine and endocrine. Exocrine tumors are the most common type of pancreatic cancer, accounting for 96% of all cases3. Adenocarcinoma, a sub-type of exocrine tumors, comprises of 95% of all exocrine tumors1.

Because the signs and symptoms of pancreatic cancer are non-specific and may not appear until the disease has spread to other sites, approximately 80% of patients are not candidates for surgery2, instead receiving chemotherapy as the mainstay of their therapy. The majority of these patients receive gemcitabine-based therapy during either adjuvant/neoadjuvant treatment or during first- or second-line therapy for metastatic disease 6.

About ONIVYDE [pronounced \ ‘on – ih – vide \]

ONIVYDE (irinotecan liposome injection), also known as MM-398 or "nal-IRI," is a novel encapsulation of irinotecan in a liposomal formulation. The activated form of irinotecan is SN-38, which functions by inhibiting topoisomerase I (an essential enzyme involved in DNA transcription and replication) and promoting cell death. ONIVYDE was recently approved by the U.S. Food and Drug Administration in combination with fluorouracil and leucovorin for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy. For full prescribing information, including Boxed WARNING, please visit www.ONIVYDE.com.