Kineta, Inc. announced updated clinical data from its ongoing VISTA-101 Phase 1/2 clinical trial evaluating KVA12123, an anti-VISTA monoclonal antibody, as both a monotherapy and in combination with Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), in patients with advanced solid tumors. The data, presented at the Society for Immunotherapy in Cancer (SITC) in Houston, TX, highlights encouraging clinical responses and a favorable safety profile.
The VISTA-101 trial is designed to assess the safety and efficacy of KVA12123 in patients with advanced solid tumors who have limited treatment options. The study includes both a monotherapy arm and a combination arm with pembrolizumab to evaluate the potential synergistic effects of targeting VISTA and PD-1 pathways.
Monotherapy Arm Results
The monotherapy arm of the trial, which has fully enrolled 24 patients, evaluated KVA12123 at doses ranging from 3 to 1000 mg administered every two weeks. As of the data cutoff date of October 18, 2024, 19 patients had at least one follow-up scan, and 13 of these patients experienced stable disease according to iRECIST criteria. Notably, one patient with non-small cell lung cancer (NSCLC) who had failed six prior lines of therapy, including checkpoint inhibitor (CPI) therapy, experienced stable disease lasting 60 weeks. Nine of the 24 monotherapy patients had prior CPI exposure.
Combination Therapy Arm Results
The combination therapy arm, evaluating KVA12123 in combination with 400 mg pembrolizumab every six weeks, has enrolled nine patients in the first two cohorts with KVA12123 doses of 30-100 mg Q2W. Early results indicate promising clinical activity, with confirmed partial response (PR) observed in one mucoepidermoid carcinoma patient showing a 54% reduction in target lesions and a confirmed complete response (CR) in non-target lesions. Additionally, one renal cell carcinoma patient who had progressed on prior CPI therapy experienced stable disease with a 24% reduction in target lesions. Enrollment in the remaining two combination cohorts is expected to be completed by year-end.
Safety and Tolerability
A key highlight of the VISTA-101 trial is the favorable safety profile of KVA12123. No dose-limiting toxicities (DLTs) have been observed in any patient at any dose level in either the monotherapy or combination arms. The treatment has been well-tolerated, with few adverse events reported.
Expert Commentary
"We are pleased to present our progress on the VISTA-101 clinical trial at SITC this year, with the initial clinical response data emerging from the study. We have observed promising clinical responses in this advanced cancer patient population. KVA12123 has the potential to be a new alternative for patients with hard-to-treat cancers," said Jason Henry, M.D. Thierry Guillaudeux, Ph.D., Chief Scientific Officer of Kineta, added, "The safety profile of KVA12123 to date has been remarkable in the monotherapy as well as in combination cohorts. Initial read-outs demonstrated that KVA12123 is not only safe but exhibits potential clinical benefit for some patients as either monotherapy or combination and may offer patients a novel approach to address immunosuppression in the tumor microenvironment and better manage solid tumor cancers."
About KVA12123 and VISTA
KVA12123 is a VISTA (V-domain Ig suppressor of T cell activation) blocking immunotherapy being developed as a twice-weekly monoclonal antibody infusion. VISTA is a negative immune checkpoint that suppresses T cell function in various solid tumors. High VISTA expression in tumors correlates with poor survival in cancer patients and has been associated with a lack of response to other immune checkpoint inhibitors. KVA12123 is designed to address immune suppression in the tumor microenvironment with a mechanism of action that is differentiated and complementary with T cell-focused therapies.
