Merrimack touts four at 2014 ASCO

Planning underway for Phase 2 studies for MM-151 in colorectal cancer and MM-141 in front-line pancreatic cancer

Lloyd Dunlap
CHICAGO—Merrimack Pharmaceuticals Inc. presented Phase 1 clinical data from studies of MM-151, MM-141, MM-111 and MM-121 at the 2014 annual meeting of the American Society of Clinical Oncology (ASCO). Data from these studies support the clinical advancement of Merrimack’s novel antibody therapeutics, the company reported in the news release detailing the clinical findings.
 
“We are excited to announce Phase 1 results for MM-151 and MM-141—two antibody therapeutics engineered with insights from our systems biology approach. This progress continues to support our goal of transforming cancer care by developing therapeutics that target key pathways responsible for tumor growth and survival. We look forward to initiating biomarker-directed Phase 2 studies with MM-151 and MM-141,” said Dr. Ulrik Nielsen, co-founder and chief scientific officer at Merrimack, in the news release.
 
Nielsen tells DDNews that Merrimack looks at biology in a different way to understand pathways. “More protein than genomics,” he says, using computer models, “bottom up—not big data—to study system dynamics and what happens when they are perturbed.”
 
Preliminary results from a Phase 1 study of MM-151, a novel oligoclonal anti-EGFR antibody combination, in patients with refractory solid tumors suggested clinical activity in colorectal cancer with an acceptable safety profile consistent with EGFR inhibition. Planning is underway for a Phase 2 study testing MM-151 in colorectal cancer.
 
“EGFR receptors are important and complicated to regulate,” Nielsen notes. “There’s tons of signal downstream even if the signal is small proximally. Signal amplification figures in as well. How can you best inhibit it?” To do so, Nielsen says, MM-151 “gangs up” on the receptor with complementary binding.
 
In the first cohort, after more than 80 weeks, partial responses (PR) were observed in two colorectal cancer patients and a total of eight patients (29 percent) had stable disease (SD) for greater than four months. Planning is underway for a Phase 2 trial to evaluate MM-151 in colorectal cancer.
 
Merrimack also reported on the results of a Phase 1 dose-escalation study in patients with advanced solid tumors that tested the tolerability and safety of MM-141, a novel tetravalent bispecific antibody inhibitor which targets both IGF-1R and ErbB3. MM-141 blocks and degrades complexes containing IGF-1R and ErbB3 receptors, leading to the downstream inhibition of tumor pro-survival signaling. Preclinical studies have shown that MM-141 has higher activity compared to a mixture of separate anti-IGF-1R and ErbB3 antibodies.
 
This clinical study enrolled three arms: MM-141 as a monotherapy, MM-141 in combination with everolimus and MM-141 in combination with nab-paclitaxel and gemcitabine. Data presented at ASCO’s annual meeting detailed the completion of the monotherapy arm. There were no dose-limiting toxicities observed in the monotherapy arm at any dose level. The most common adverse events that were not deemed related to MM-141 monotherapy were vomiting, nausea, fatigue, abdominal pain and dyspnea.
 
MM-141 monotherapy showed preliminary activity with disease stabilization observed in patients with Ewing’s sarcoma and parotid gland carcinoma. Planning is underway for a Phase 2 study of MM-141 in combination with nab-paclitaxel and gemcitabine in front-line pancreatic cancer care.
 
Merrimack also presented a Phase 1 multi-arm study of MM-111 in combination with standard-of-care regimens in multiple tumor types as well as a Phase 1 study of MM-121 in combination with cetuximab and irinotecan in patients with advanced solid cancers.
 
A total of 86 patients with advanced HER2+ cancers were enrolled in the MM-111 study. Across all dosing regimens, the overall clinical benefit rate, defined as complete response, PR and SD for at least four months, was 55 percent in 86 evaluable patients.
 
Finally, a Phase 1 trial assessed the safety, tolerability and pharmacokinetic properties of MM-121 in combination with cetuximab or with cetuximab and irinotecan in patients with advanced solid cancers. MM-121 is a fully human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin.
 
Across all dosing regimens, 18 of 48 (37.5 percent) of patients achieved a best overall response of SD or PR, 14 of 48 (29.2 percent) had SD and four of 48 (8.3 percent) had a PR. Of the four patients who had PR, two had KRAS wild-type colorectal cancer, one had cholangiocarcinoma and one had NSCLC. One colorectal cancer patient previously treated with cetuximab and irinotecan achieved a PR on the MM-121/cetuximab/irinotecan combination. One head and neck cancer patient who previously received cetuximab achieved a durable response of SD on the MM-121/cetuximab combination. Further studies with these combinations are being evaluated.
 
Merrimack is a biopharmaceutical company discovering, developing and preparing to commercialize innovative medicines paired with companion diagnostics for the treatment of cancer. Merrimack seeks to gain a deeper understanding of underlying cancer biology through its systems biology-based approach and develop new insights, therapeutics and diagnostics to improve outcomes for cancer patients. Merrimack currently has six oncology therapeutics in clinical development and three additional candidates in late-stage preclinical development.

Lloyd Dunlap

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