avasopasem (GC4419)

P1, N=35, Recruiting, The University of Texas Health Science Center at San Antonio | Not yet recruiting --> Recruiting | Trial completion date: Jul 2028 --> Oct 2028 | Trial primary completion date: Jul 2027 --> Oct 2027

P1, N=35, Not yet recruiting, The University of Texas Health Science Center at San Antonio

AVA demonstrated a significant protective effect against sepsis-induced lung injury through its antioxidant and anti-inflammatory properties. The most effective dose was determined to be 10 mg/kg. These findings suggest the potential use of AVA as an adjunctive agent in sepsis treatment.

Finally, AVA significantly accelerated wound closure in a murine model of wound healing post RT. Our data suggest that AVA may be a promising combination strategy for nRT therapy in STSs.

P3, N=455, Completed, Galera Therapeutics, Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Aug 2023

Co-treatment with DMs and P-AscH selectively enhanced tumor radiosensitization by increasing oxygen consumption and H0 fluxes even in tumor models which are known to be resistant to oxidative stressors (HT29). In contrast, each agent conferred a radioprotective effect in the rectum. Combination therapy with DMs and P-AscH may represent a novel, potent approach to target dysregulated redox metabolism in colorectal tumors.

This review describes the preclinical and clinical studies which led to, and supported the NDA, and assesses the potential utility of avasopasem clinically. Avasopasem manganese appears to effectively mitigate severe OM associated with concomitant chemoradiation used in the treatment of head and neck cancers, as well as cisplatin-associated renal toxicity in the absence of impairing tumor response.

This study is funded by Galera Therapeutics, Inc. Conclusions At 1-year follow-up, AVA appears to reduce cisplatin-related CKD in the study population and may also reduce cisplatin-related AKI. These results carry significance beyond CRT for HNC, potentially impacting platinum-containing regimens in other cancers.

In order to identify these potential nodes of therapeutic actionability, we leveraged a phase I/II dose escalation clinical trial of SBRT with a radiomodulating agent, GC4419, undertaken in patients with locally advanced PDAC...This has revealed an interplay between members of the tumor microenvironment whereby immunosuppressive pathways appear to prevail over immunostimulatory signals in nonresponders. Understanding which pathways are enriched in those patients at highest risk for local recurrence may provide insight into novel therapeutic strategies that can be implemented concurrently with radiation therapy.

The radiotherapeutic effect can be vastly increased with superoxide dismutase mimetics, both within and outside the treatment field. Combination therapy requires screening of schedules regarding timing, drug dosage, and IR dose and fractionation to achieve optimal tumoricidal effects. SODm synergize with IR acting on various molecular targets that can be harnessed to overcome treatment resistance.