Longer than expected PFS for murlentamab when combined with FTD/TPI, particularly in patients with medium/high AMHRII expression, along with immune cascade activation in the tumor micro-environment
Paris and Toulouse, France, July 5, 2019 – GamaMabs Pharma, a clinical stage biotechnology company developing optimized therapeutic antibodies targeting the Anti-Müllerian Hormone Receptor II (AMHRII) for the treatment of cancer, announces the oral presentation today of clinical data from its phase 2 study of murlentamab in metastatic colorectal cancer (mCRC), at the ESMO World Congress on Gastrointestinal Cancer in Barcelona (Spain).
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 tumor cells, with respectively 83% and 75% patients free of progression at 4 and 6 months. 1.7-fold and 3.6-fold tumor 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 tumor 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% of the tumor biopsied at treatment initiation in the metastatic setting, confirming our previous findings in primary tumors,” 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 tumor microenvironment by murlentamab, from macrophage to cytotoxic T lymphocyte activation.”
“Following the release in May of data on murlentamab in gynecological cancers at the ASCO annual meeting, presenting these phase 2 study results in mCRC at the ESMO World GIC congress represents another key milestone for GamaMabs,” said Stéphane Degove, Chief Executive Officer at GamaMabs Pharma. “We are thrilled by the significant prolonged PFS in advanced AMHRII-medium/high mCRC patients treated by murlentamab and FTD/TPI, which encourages us to pursue the development of murlentamab in this indication with high unmet needs.”
Results are being presented at the ESMO World Congress on Gastrointestinal Cancer on July 3-6 in Barcelona (Spain) as an oral presentation during the Emerging New or Combination Drugs in GI Cancer session on Friday, July 5, 8:00 – 9:20 a.m. (local time), and as a poster presentation.
Abstract # 214: ‘Phase 2 study results of murlentamab, a monoclonal antibody targeting the Anti-Mullerian-Hormone-Receptor II (AMHRII), acting through Tumor-Associated Macrophage engagement in advanced/metastatic colorectal cancers’ by E Van Cutsem and co-authors.
Murlentamab is a first-in-class glyco-engineered (low-fucose) monoclonal antibody selectively targeting AMHRII-expressing tumors. 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-tumor activity through tumor-associated macrophages reprogramming, resulting in enhanced tumor phagocytosis and subsequent cytotoxic T cell reactivation.
About GamaMabs Pharma
GamaMabs Pharma, a French immuno-oncology biotechnology company, is the leader in the development of optimized antibodies targeting AMHRII for the treatment of cancer. GamaMabs’ first-in-class proprietary therapeutic monoclonal antibodies have the potential for broad applications in cancer. Murlentamab, which targets the Anti-Müllerian Hormone Receptor II (AMHRII/MISR2), is in phase 2 stage of development in various solid tumors. The company develops low-fucose EMABling® antibodies (license granted by LFB) with increased tumor cell killing properties through a breakthrough activation of immune cells. GamaMabs also has a licensing agreement with MedImmune (USA) to develop an Antibody Drug Conjugate targeting cancer.