11-27-2013, 07:32 AM
Merrimack Pharmaceuticals and Sanofi have announced that its drug MM-121, an ErbB3 antibody, did not meet the primary endpoint in a Phase II trial on women with ER/PR+, HER2- breast cancer. This follows on from a previous failure to meet the primary endpoint in a phase II trial on ovarian cancer patients, which we referred to previously on this forum (http://www.biotechnologyforums.com/thread-2581.html). However, Merrimack remains firmly optimistic that the biomarker results of these studies confirms that a sub-population of ER/PR+, HER2- breast cancer patients with biomarkers mechanistically linked to ErbB3 signalling may benefit from the drug. The company confirmed that these are the same ErbB3-signalling-linked biomarkers that were indicated in the ovarian cancer Phase II trial. ErbB3 (HER3) is a member of the epidermal growth factor receptor (ErbB; EGFR) family.
The most recent phase II trial was carried out to determine the effect of adding MM-121 to exemestane compared to exemestane in the absence of MM-121. The trial, on 118 patients who had previously failed anti-oestrogen therapy, was double-blinded, randomised and placebo-controlled and the primary endpoint was progression-free survival (PFS). Although the trend was in favour of the MM-121-containing treatment, the primary end-point was not met. However, similarly to the ovarian cancer trial, a sub-population comprising approximately one third of the 55 biomarker-evaluable patients was identified. The undisclosed markers, linked to ErbB3 signalling, were confirmed to be the same as those identified in the ovarian cancer trial in which MM-121 was evaluated in conjunction with paclitaxel. Gavin MacBeath, the co-founder and Vice-President of translational research at Merrimack, maintained that the data ‘serves to further confirm our original biomarker hypothesis’ and that ‘These data further implicate ErbB3 signalling as a general mechanism of resistance to standard-of-care therapies.’ Safety data indicated that adverse events data was similar between the control and treatment arms and no increase in serious adverse events were reported in the treatment arm.
In a second phase II trial, MM-121 was tested in combination with paclitaxel on 99 patients. Pathologic complete response (pCR) rate, which is based on measurement of absence of invasive cancer in breast and lymph node tissue after neoadjuvant therapy and is accepted to be a strong indicator for prolonged disease-free survival, was measured although no primary endpoint was set. pCR was found to be 10.8% in the presence of MM-121 as opposed to 3.3% in its absence. Translational analysis is on-going.
Merrimack and Sanofi will continue to pursue their biomarker theory.
Sources
http://www.fiercebiotech.com/press-relea...hase-2-e-0 [Accessed 26 November 2013].
SCHOEBERL, B. et al., 2010. An ErbB3 antibody, MM-121, is active in cancers with ligand-dependent activation. Cancer research, 70(6), pp. 2485-2494
http://www.fiercebiotech.com/press-relea...-sar256212 [Accessed 30 October 2013].
The most recent phase II trial was carried out to determine the effect of adding MM-121 to exemestane compared to exemestane in the absence of MM-121. The trial, on 118 patients who had previously failed anti-oestrogen therapy, was double-blinded, randomised and placebo-controlled and the primary endpoint was progression-free survival (PFS). Although the trend was in favour of the MM-121-containing treatment, the primary end-point was not met. However, similarly to the ovarian cancer trial, a sub-population comprising approximately one third of the 55 biomarker-evaluable patients was identified. The undisclosed markers, linked to ErbB3 signalling, were confirmed to be the same as those identified in the ovarian cancer trial in which MM-121 was evaluated in conjunction with paclitaxel. Gavin MacBeath, the co-founder and Vice-President of translational research at Merrimack, maintained that the data ‘serves to further confirm our original biomarker hypothesis’ and that ‘These data further implicate ErbB3 signalling as a general mechanism of resistance to standard-of-care therapies.’ Safety data indicated that adverse events data was similar between the control and treatment arms and no increase in serious adverse events were reported in the treatment arm.
In a second phase II trial, MM-121 was tested in combination with paclitaxel on 99 patients. Pathologic complete response (pCR) rate, which is based on measurement of absence of invasive cancer in breast and lymph node tissue after neoadjuvant therapy and is accepted to be a strong indicator for prolonged disease-free survival, was measured although no primary endpoint was set. pCR was found to be 10.8% in the presence of MM-121 as opposed to 3.3% in its absence. Translational analysis is on-going.
Merrimack and Sanofi will continue to pursue their biomarker theory.
Sources
http://www.fiercebiotech.com/press-relea...hase-2-e-0 [Accessed 26 November 2013].
SCHOEBERL, B. et al., 2010. An ErbB3 antibody, MM-121, is active in cancers with ligand-dependent activation. Cancer research, 70(6), pp. 2485-2494
http://www.fiercebiotech.com/press-relea...-sar256212 [Accessed 30 October 2013].
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