Merrimack Pharmaceuticals, Inc. and Baxalta Incorporated jointly announced the initiation of a phase 1 clinical study of Merrimack's oligoclonal EGFR (epidermal growth factor receptor) inhibitor, MM-151, in combination with Onivyde (irinotecan liposome injection) plus fluorouracil (5-FU) and leucovorin in patients with RAS wild-type metastatic colorectal cancer. Data from a prior phase 1 study of MM-151 supports further clinical evaluation of the investigational therapy in patients with metastatic colorectal cancer. The initiation of this study advances the development path for Onivyde.

"Metastatic colorectal cancer remains a deadly disease with only 11% of patients surviving five years or longer," said Dr. Emily Chan, principal investigator, Associate Professor of Medicine and GI Medical Oncologist, Vanderbilt-Ingram Cancer Center. "As our understanding of the dynamics of cancer cells increases, we are able to develop and explore novel targeted combination therapies to combat this deadly disease. This study is a significant step forward toward addressing this unmet medical need, and providing a potential new treatment option to patients facing this deadly disease."

This phase 1 study will assess the safety and tolerability of the combination of MM-151, a novel antibody mixture of three human antibodies designed to target EGFR which promotes tumor growth, and ONIVYDE, also known as MM-398 or "nal-IRI," plus 5-FU and leucovorin as first or second-line treatment in patients with RAS wild-type metastatic colorectal cancer.

"We are excited to initiate this phase 1 clinical study, which will enable us to evaluate MM-151 in combination with the ONIVYDE regimen," said J. Marc Pipas, M.D., Medical Director at Merrimack. "Preclinically, MM-151 has shown superior inhibition of the EGFR pathway compared to FDA approved EGFR inhibitors. Combining MM-151 with the ONIVYDE regimen represents an exciting opportunity to investigate a potential new treatment regimen for patients with metastatic colorectal cancer."

The trial will determine the side effect profile of MM-151 in combination with ONIVYDE plus 5-FU and leucovorin and recommended dose for subsequent trials with this combination. Eligible patients for the study must have metastatic disease, have had no prior exposure to irinotecan or an EGFR inhibitor, and have received no more than one prior line of treatment for metastatic disease. Merrimack plans to conduct the study at multiple sites in the United States. Merrimack will be solely responsible for the funding and execution of the phase 1 study.

Merrimack and Baxalta have entered into an exclusive licensing agreement to develop and commercialize ONIVYDE outside of the United States. PharmaEngine, Inc. (Taipei, Taiwan) holds the rights to commercialize Onivyde in Taiwan and received the Taiwan FDA approval of Onivyde on October 22, 2015.

MM-151 is Merrimack's wholly owned oligoclonal therapeutic mixture consisting of three fully-human monoclonal antibodies designed to bind and inhibit signaling of the epidermal growth factor receptor (EGFR). EGFR-mediated signaling promotes the growth and survival of cancer cells and has long been recognized as an important drug target in several types of cancer, including colon, lung, breast, pancreatic, and head and neck cancers. MM-151 has previously been tested in a phase 1 dose-escalation clinical trial in patients with advanced solid tumors.

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 approved by the US 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.