GamaMabs Pharma, developing optimized therapeutic antibodies targeting the Anti-Müllerian Hormone Receptor II (AMHRII) for the treatment of cancer, announces the oral presentation of clinical data from its phase II study of murlentamab in metastatic colorectal cancer (mCRC).
In combination with trifluridine/tipiracil (FTD/TPI – Lonsurf®), progression-free survival (PFS) was longer than expected (40% and 31% at 4 and 6 months respectively). This was especially pronounced in patients with more than 20% AMHRII-positive tumour cells, with respectively 83 per cent and 75 per cent patients free of progression at 4 and 6 months. 1.7-fold and 3.6-fold tumour growth rate decrease was observed with murlentamab single agent and murlentamab combined with trifluridine/tipiracil, respectively.
Immune activation under murlentamab was consistently observed in the tumour microenvironment (macrophage and T-cell activation) and in peripheral blood (monocytes and neutrophils activation). No serious adverse events related to murlentamab were reported.
Fourteen patients treated with murlentamab as a single agent (SA) and 15 patients treated in combination with FTD/TPI have been evaluated for efficacy in two parallel non-randomized cohorts.
“These first clinical and pharmacodynamic data are really encouraging for these patients who have so few options,” said Professor Eric Van Cutsem, University Hospitals Leuven (Belgium), principal investigator of the study. “These results support further development of murlentamab in combination with standard chemotherapies and/or immunological agents in colorectal cancers.”
“AMHRII expression was found in more than 80 per cent of the tumour biopsied at treatment initiation in the metastatic setting, confirming our previous findings in primary tumours,” said Dr. Isabelle Tabah-Fisch, Chief Medical Officer at GamaMabs Pharma. “Besides the encouraging clinical data, the pharmacodynamics changes under murlentamab confirm the rewire of the tumour microenvironment by murlentamab, from macrophage to cytotoxic T lymphocyte activation.”
Murlentamab is a first-in-class glyco-engineered (low-fucose) monoclonal antibody selectively targeting AMHRII-expressing tumours. AMHRII, an embryonic receptor, is re-expressed in a variety of solid tumors. Murlentamab is currently being evaluated in two clinical trials, phase 1b in gynecological cancers and phase 2 in advanced or metastatic colorectal cancers. Murlentamab exerts its anti-tumour activity through tumour-associated macrophages reprogramming, resulting in enhanced tumour phagocytosis and subsequent cytotoxic T cell reactivation. [APBN]