Sanofi/Merrimack's anticancer-booster MAb fails to overcome resistant lung cancer
This article was originally published in Scrip
Its MM-121 monoclonal antibody is an important product for Merrimack Pharmaceuticals. The company’s Network Biology platform identified ErbB3, the antibody’s target, as an intervention point in cancers which have become resistant to other treatments. So the failure of the drug in a 50 person Phase II trial in erlotinib-resistance non-small cell lung cancer (NSCLC) could have repercussions beyond this one trial.
According to Merrimack, MM-121 is designed to inhibit cancer growth directly, restore drug sensitivity to resistant tumors and delaying the emergence of tumor resistance. In addition to the NSCLC trial, Merrimack in partnership with Sanofi is testing MM-121 currently in Phase II studies in advanced ovarian cancer, hormone sensitive breast cancer, and HER2-negative neoadjuvant breast cancer. In those studies, MM-121 is being used in conjunction with paclitaxel, paclitaxel and exemestane, respectively.
Endpoints
Erlotinib is an EGFR targeted therapy, commonly used in the treatment of NSCLC. But many erlotinib patients acquired resistance to EGFR-TK inhibitor therapy. Merrimack was asked to demonstrate that MM-121 would allow 40% of such patients four months of progression free survival. MM-121 was used in combination with erlotinib in NSCLC patients whose disease had progressed.
The trial could not reach that endpoint. Merrimack has not put out information on how many patients, if any, met the endpoint, or whether there was an extension of progression-free disease at all.
A secondary objective of the study was to evaluate tissue samples from patient biopsies to assess whether the biomarker hypothesis behind MM-121 could be translated into a clinical setting.
Akos Czibere, who is the Senior Medical Director of the MM-121 program said that although the company was disappointed by the overall clinical result it was “encouraged” by a preliminary biomarker analysis which Merrimack believed would be important for identification patients in which its anti-resistance would be effective.
The drug is still being evaluated in two additional NSCLC patient groups in which resistance to EGFR-TK inhibitors is known or implied, those with chemotherapy-treated metastatic disease and those with a known EGFR-activating mutation.
Investor sentiment
The negative news meant that Nasdaq-listed Merrimack's stock took an initial 2.4% hit, opening at $6.06 on the day of the news. However, by the end of the day its shares recovered back to the earlier $6.21 level.
Related stories
Merrimack forms partnership with cancer treatment centres to access tumour samples