First clinical proof-of-concept for arginase inhibitors in cancer immunotherapy

The compound was used both as a monotherapy and in combination with a checkpoint inhibitor pembrolizumab (Keytruda®, Merck &Co). Results for the cohort of the microsatellite stable (MSS) colorectal cancer patients were reported. This cancer type is very refractory to standard therapies and in particular to immune checkpoint inhibitors. Confirmed partial response and stable disease in 27% of patients were observed in patients in the monotherapy arm. When combined with pembrolizumab, partial response was observed in 37% of patients, while the overall response rate (ORR) increased from 3% in monotherapy to 7% in the combo arm (versus 0-1% reported for checkpoint inhibitors) and the progression free survival rate at 6 months doubled compared to pembrolizumab alone.

The results presented by Calithera Biosciences validate arginase as a novel target in oncology and provide a clinical proof-of-concept for arginase inhibitors as new therapies for patients with refractory cancers. Importantly, the presented data demonstrated that inhibition of arginase is safe at therapeutic doses in patients.

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OncoArendi Therapeutics develops novel arginase inhibitors and its frontrunner, OATD-02, is a more potent molecule with a unique profile that differentiates it from INCB001158. OATD-02, which is currently in the final stages of preclinical development, has already raised the interest of many pharmaceutical and biotechnology companies that may benefit from including an arginase inhibitor in their product portfolio of cancer immunotherapies. Clinical proof-of-concept, validation of the target and confirmation of safety and tolerability of therapeutic doses for INCB001158, clearly reduce the translational risk and increase the attractiveness of OATD‑02 for a potential partnering transaction.[/vc_column_text][/vc_column][/vc_row]

Magda KućmaFirst clinical proof-of-concept for arginase inhibitors in cancer immunotherapy