Merrimack Pharmaceuticals, Inc., a clinical-stage oncology company focused on biomarker-defined cancers, today announced top-line results from the CARRIE study, a randomized Phase 2 trial evaluating the addition of MM-141 (istiratumab) to standard-of-care treatment in patients with previously untreated metastatic pancreatic cancer and high serum levels of free Insulin-like Growth Factor-1 (IGF-1). The study did not meet its primary or secondary efficacy endpoints in patients who received MM-141 in combination with nab-paclitaxel and gemcitabine, compared to nab-paclitaxel and gemcitabine alone. These results were consistent in all subgroups analyzed. Based on these results, Merrimack will not devote additional resources to the development of MM-141.
Merrimack plans to present the complete data from this Phase 2 study at an upcoming medical oncology meeting.
“Pancreatic cancer is the third leading cause of cancer-related death in the Unites States and a very difficult cancer to treat,” said Sergio Santillana, M.D., MSc., Chief Medical Officer of Merrimack. “Although we were unsuccessful in our effort to improve the standard of care for these patients, we want to express our gratitude to our investigators and our team, and, of course, to the patients and their families for their support and participation in the CARRIE study.”
“While these results are disappointing, looking forward our focus remains on the continued development of our deep, wholly-owned pipeline, including two clinical programs, MM-121 and MM-310, with data readouts expected in 2018,” said Richard Peters, M.D., Ph.D., President and CEO of Merrimack.
MM-121 (seribantumab), a monoclonal antibody targeting the HER3 (ErbB3) receptor, is being tested in combination with standard-of-care treatment in two randomized Phase 2 studies: SHERLOC, in patients with non-small cell lung cancer, and SHERBOC in patients with metastatic breast cancer. Both studies are enrolling patients with high tumor expression of heregulin, the signal for the HER3 receptor. Top-line results from the SHERLOC study are expected in 2H 2018.
MM-310, an antibody-directed nanotherapeutic targeting the EphA2 receptor, is currently being tested in a Phase 1 study in solid tumors, with safety data and the maximum tolerated dose expected in 2H 2018.
The CARRIE study is a global, double-blinded, placebo-controlled, randomized Phase 2 trial, evaluating MM-141 in patients with previously untreated metastatic pancreatic cancer. Prior to enrollment, patients were screened for high serum levels of free IGF-1, a prevalent biomarker in approximately 50% of patients with pancreatic cancer that is believed to be associated with more aggressive forms of the disease. The trial enrolled 88 patients who were randomized 1:1 to treatment and control arms to assess MM-141, in combination with the standard-of-care chemotherapy (nab-paclitaxel and gemcitabine), versus chemotherapy plus placebo.
The primary endpoint of the study is progression-free survival, while secondary endpoints include objective response rate, disease control rate, duration of response, overall survival and safety. Merrimack initiated the CARRIE study in May 2015 and completed enrollment in June 2017. MM-141 (istiratumab) is Merrimack’s wholly owned, fully human, bispecific, tetravalent monoclonal antibody, targeting receptor complexes containing the Insulin Like Growth Factor 1 Receptor (IGF-1R) and ErbB3 (HER3) cell surface receptors to block tumor survival signals. IGF-1R and HER3 complexes cooperate to activate the PI3K/AKT/mTOR pathway, a major signaling pathway that allows tumor cells to grow and develop resistance to chemotherapy. MM-141 is designed to suppress the PI3K/AKT/mTOR pathway by binding to both the IGF-1R and HER3 receptors.