Merrimack Pharmaceuticals, Inc. today announced it filed an amendment to its ongoing Phase 2 clinical study of MM-121 (seribantumab) in patients with heregulin-positive non-small cell lung cancer (NSCLC) with the U.S. Food and Drug Administration (FDA). The amendment includes a change in primary endpoint to overall survival to enable a potential registration opportunity for MM-121.
"We believe MM-121 has the potential to address the pervasive clinical problem of resistance in cancer. This amendment is intended to accelerate development of this new treatment option for heregulin-positive non-small cell lung cancer patients who are resistant to standard-of-care therapies," said Robert Mulroy, Merrimack's President and CEO. "The financing we announced today will allow us to independently advance and retain sole ownership of MM-121. In light of this amendment, we are focusing the development of MM-121 on this indication."
MM-121 is a fully human monoclonal antibody targeting ErbB3. The ongoing clinical study in NSCLC is an open-label, biomarker–selected randomized study of MM-121 in combination with docetaxel or pemetrexed compared to docetaxel or pemetrexed alone, in patients with heregulin-positive, locally advanced or metastatic NSCLC. Three prior Phase 2 clinical studies demonstrated that a subset of biomarker positive patients treated with MM-121 had a statically significant reduction in the risk of progression, with hazard ratios in a range of 0.26 – 0.37.
"We are pleased with investigator enthusiasm for the trial, which highlights the high unmet medical need in metastatic non-small cell lung cancer. Consistent with our previous Phase 2 study, more than half of the patients screened to date have been biomarker positive," said Akos Czibere, M.D., Ph.D., MM-121 Global Development Lead at Merrimack. "Amending this study design is a significant step forward in the development path for MM-121 in non-small cell lung cancer, where there is an urgent need for novel, biomarker-directed therapies to help patients battle drug resistance. We look forward to advancing this therapy and providing a potential new treatment option for this patient population."
Under the filed amendment, Merrimack expects to enroll approximately 280 heregulin-positive patients who will be randomized (2:1) to receive MM-121 plus the investigator's choice of docetaxel or pemetrexed, or the investigator's choice of docetaxel or pemetrexed alone. Eligible patients for the study must have failed prior treatment with no more than three lines of therapy for locally advanced or metastatic disease and, where applicable, prior PDL1 therapy. The amended primary endpoint of the study will be overall survival. Secondary endpoints include progression free survival, objective response rate, safety and quality of life measures. Merrimack continues to open study sites in the United States, Canada, Asia and Europe. With this updated study design, Merrimack expects survival data in 2018.
About MM-121 (Seribantumab)
MM-121 is Merrimack's wholly owned, fully human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, MM-121 is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner.
Merrimack is pursuing this Phase 2 study based on encouraging results from a broad MM-121 Phase 2 program which identified heregulin mRNA expression as a potential prognostic factor of poor response to standard-of-care therapy across multiple cancers. The results also indicated that patients with heregulin-positive tumors experienced a longer time to progression when they received a combination of MM-121 with their standard-of-care therapy as compared to patients who received the standard therapy alone. Across the three different standard-of care combination regimens, a consistent safety profile demonstrated a modest but tolerable increase in adverse events. An extensive translational component of the MM-121 clinical program was designed to establish clinically meaningful biomarkers that were initially identified using Merrimack's systems biology approach and preclinical studies
Merrimack is a fully integrated biopharmaceutical company that views cancer as a complex engineering challenge. Through systems biology, which brings together the fields of biology, computing and engineering, Merrimack aims to decrease uncertainty in drug development and clinical validation, and move discovery efforts beyond trial and error. Such an approach has the potential to make individualized treatment of patients a reality. Merrimack's first commercial product, ONIVYDE™ (irinotecan liposome injection), was approved by the U.S. FDA on October 22, 2015. With four additional candidates in clinical studies, several in preclinical development and multiple biomarkers designed to support patient selection, Merrimack is building one of the most robust oncology pipelines in the industry. For more information, please visit Merrimack's website at www.merrimack.com or connect on Twitter at @MerrimackPharma.
To the extent that statements contained in this press release are not descriptions of historical facts, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements include any statements about Merrimack's strategy, future operations, future financial position and future expectations and plans and prospects for Merrimack, and any other statements containing the words "anticipate," "believe," "estimate," "expect," "intend," "may," "plan," "predict," "project," "target," "potential," "will," "would," "could," "should," "continue," "hope" and similar expressions. In this press release, Merrimack's forward-looking statements include statements about the ability of the clinical trial amendment to create a potential registration opportunity for MM-121, the potential effectiveness and safety profile of MM-121 in certain patient populations or subpopulations, the ability to use heregulin as a predictive diagnostic, the initiation of future clinical trials and the ability to translate clinical data into future clinical success. Such forward-looking statements involve substantial risks and uncertainties that could cause Merrimack's clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, availability of data from ongoing clinical trials, expectations for regulatory approvals, development progress of Merrimack's companion diagnostics and other matters that could affect the availability or commercial potential of Merrimack's drug candidates or companion diagnostics. Merrimack undertakes no obligation to update or revise any forward-looking statements. Forward-looking statements should not be relied upon as representing Merrimack's views as of any date subsequent to the date hereof. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Merrimack's business in general, see the "Risk Factors" section of Merrimack's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 9, 2015 and other reports Merrimack files with the SEC.
Geoffrey Grande, CFA