ImmunoGenesis has initiated the first subject dosing in a multicentre Phase I/II trial of IMGS-101 (evofosfamide), the hypoxia reversal agent, in conjunction with Balstilimab and Zalifrelimab, for treating adults with certain cancer types.
The subject was dosed at the University of Texas MD Anderson Cancer Center in Houston, US.
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The open-label trial will focus on adults with locally advanced or metastatic castration-resistant prostate cancer, human papillomavirus-(HPV) negative squamous cell carcinoma of the head and neck (SCCHN), and pancreatic cancer.
It comprises a dose escalation and expansion part to assess the pharmacokinetics, efficacy, anti-tumour activity, and safety of the combination.
ImmunoGenesis Clinical Development senior vice-president Dr Charles Schweizer said: “This trial marks an exciting step forward in addressing one of the key challenges in cancer immunotherapy. Hypoxia limits T-cell infiltration and suppresses immune responses, especially in prostate, pancreatic, and head and neck cancers.
“By reversing hypoxia, IMGS-101 may restore T-cell access to tumours, enhancing the effectiveness of checkpoint inhibitors and potentially transforming outcomes in these hard-to-treat cancers.”
Also referred to as Evofosfamide, IMGS-101 is stated to be a 2-nitroimidazole prodrug of the cytotoxin bromo-isophosphoramide mustard (Br-IPM) that was initially developed as a hypoxia-activated prodrug.
Dr Michael Curran of MD Anderson and the founder of ImmunoGenesis demonstrated in his lab that IMGS-101 has a unique ability to overcome one of the most significant immunosuppressive barriers by reversing hypoxia.
The therapy is claimed to have ‘restored’ the function of T-cells in pre-clinical models and during a Phase I study, highlighting the early signs of synergy with checkpoint inhibitors.
IMGS-101 is being developed as a hypoxia-reversal agent aimed at conditioning tumours to respond to checkpoint inhibition.
Balstilimab and Zalifrelimab, both developed by the immuno-oncology company Agenus, are a fully human monoclonal immunoglobulin G1 targeting programmed cell death protein 1 (PD-1) and a cytotoxic T-lymphocyte associated antigen 4 (CTLA-4), respectively.
