Update on Phase 1/2 KVA12123 Trial in Advanced Solid Tumor Patients

Kineta, a clinical-stage biotechnology firm, has reported positive results from its ongoing VISTA-101 Phase 1/2 clinical trial. The trial is assessing KVA12123, an innovative VISTA blocking immunotherapy, in patients with advanced solid tumors. KVA12123 has successfully cleared the initial four monotherapy dosages and the first combination group with Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab). The drug has shown excellent tolerability with no dose limiting toxicities or cytokine related adverse events observed at any dosage level.

KVA12123 has also demonstrated a robust and proportional induction of pro-inflammatory biomarkers, which are crucial for potent anti-tumor activity, indicating the drug’s on-target effects in blocking VISTA. Kineta's CEO, Shawn Iadonato, expressed optimism about the biomarker data and the safety profile of KVA12123, suggesting its potential to overcome immunosuppression in the tumor microenvironment. The company anticipates fully enrolling the Phase 1 part of the trial by April 2024.

In the VISTA-101 trial, 18 patients have been dosed with KVA12123. The primary goals are to evaluate the drug's safety and tolerability and to determine the recommended Phase 2 dose. The patients involved in the study have received multiple prior treatments, including chemotherapy, radiation, and immunotherapy. KVA12123 has been well tolerated in all dosages, and no dose limiting toxicities have been observed.

The drug has induced dose proportional levels of pro-inflammatory biomarkers including CXCL10, CCL2, CCL3, and CCL4, which are essential for strong anti-tumor activity. Consistent increases in anti-tumor non-classical monocytes, NK cells, and T cells have also been noted. Kineta has developed a proprietary assay to evaluate VISTA receptor occupancy on immune cells, and KVA12123 has achieved over 90% occupancy at the 30 and 100 mg doses.

Kineta is focused on developing next-generation immunotherapies, and KVA12123 is one of its main pipeline candidates. The company aims to provide novel approaches to address immune suppression in the tumor microenvironment. KVA12123 is being evaluated as a potential treatment for various cancer types, including non-small cell lung, colorectal, renal cell carcinoma, head and neck, and ovarian cancer.

VISTA is a negative immune checkpoint that suppresses T cell function in solid tumors. High VISTA expression correlates with poor survival in cancer patients and is associated with a lack of response to other immune checkpoint inhibitors. Blocking VISTA can induce a polyfunctional immune response to address immunosuppression and drive anti-tumor responses.