KEY TAKEAWAYS
- The phase I trial aimed to evaluate the efficacy and safety of K01401-020, in targeting its immunosuppressive functions within the TME for potential cancer immunotherapy.
- The first-in-human trial, K01401-020, highlights a well-tolerated non-pH-sensitive VISTA-targeting antibody. Administered singly or in combination with anti PD-1, this therapy is currently undergoing dose escalation studies for advanced solid tumors.
Cancer cells often evade immune attack by exploiting “checkpoints” that suppress immune responses. One such checkpoint is V-domain Immunoglobulin Suppressor of T cell Activation (VISTA), highly expressed in tumors and linked to poor prognosis and resistance to existing immunotherapies. Targeting VISTA emerges as a promising strategy to unleash the immune system against cancer. K01401-020, a humanized antibody with high affinity for VISTA, is being investigated as a potential weapon in this fight.
Geneviève Gueguen Dorbes and her team spearheaded the research that aimed to evaluate the efficacy and safety of K01401-020 in targeting VISTA’s immunosuppressive role in the tumor microenvironment (TME) for potential cancer immunotherapy.
The study employed human recombinant proteins and healthy donor peripheral blood mononuclear cells (PBMCs) for in vitro assays. Anti-tumor activity was assessed in human VISTA knock-in (KI) mice engrafted with MC38 cells. Repeat-dose toxicity studies were conducted using Non-Human Primates (NHP) in GLP 6- and 13-week assessments.
The results demonstrated potent inhibition of VISTA binding to key partners (PSGL-1, VSIG3, and VSIG8) regardless of pH. In PBMC in vitro assays, it stimulated monocyte activation, NK cell proliferation, and cytokine release, contributing to T cell activation.
In vivo, single-agent treatment exhibited antitumor activity in a syngeneic model by activating tumor immune responses. Additionally, combined with anti-PD-1, K01401-020 showed enhanced antitumor effects. In a 13-week NHP toxicity study, minimal and reversible observations occurred at the highest dose (100 mg/kg/inj), with transient cytokine increases at safe lower doses, suggesting a favorable safety profile.
The study concluded that K01401-020 robustly induces immune cell activation and anti-tumor responses. Demonstrating excellent tolerability in NHPs, the First-in-Human trial, evaluating its efficacy as a single agent and in combination with pembrolizumab for advanced solid tumors, underscores its potential as a promising and well-tolerated therapeutic intervention. The research is sponsored by Pierre Fabre Medicament.
Source: https://cslide.ctimeetingtech.com/immuno23hybrid/attendee/confcal/show/session/34
Clinical Trial: https://clinicaltrials.gov/study/NCT04564417
Dorbes GG. et al. ‘’Pre-clinical evaluation and safety profile of the highly selective anti-VISTA antibody K01401-020.’’ Presented at ESMO I-O 2023, Geneva, Switzerland (147P)
