VISTA-101 Trial of KVA12123 in Advanced Solid Tumors Reopens Enrollment

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Enrollment for the VISTA-101 clinical trial, a study evaluating KVA12123 for the potential treatment of advanced solid tumor cancers, has reopened.¹

To date, 30 of the estimated 39 patients have been enrolled in the trial. This includes a monotherapy arm of KVA12123 and a combination arm where KVA12123 is being evaluated with pembrolizumab (Keytruda).

The study is expected to be fully enrolled by the end of 2024.

"We believe KVA12123 has the potential to be a promising new treatment alternative for patients with cancer. Importantly, KVA12123 has demonstrated multiple synergies with both of our IFx and Delta receptor technologies and could be a promising addition to our pipeline, bringing in a potential phase 2-ready, novel checkpoint inhibitor. The expected completion of the enrollment in the phase 1 portion of the VISTA-101 trial this year is an important milestone in the continued advancement of this program, and we are pleased to work closely with the Kineta team to get patient enrollment underway again as we continue to investigate the possibility of acquiring this asset under the Agreement," said James Bianco, chief executive officer of TuHURA, in a press release.

KVA12123 is a VISTA-blocking immunotherapy. VISTA, or V-domain immunoglobulin suppressor of T-cell activation, is an immunoregulatory molecule involved in maintaining T-cell and myeloid quiescence.² VISTA is different from other immune checkpoint inhibitors in that it is expressed on naive T cells, while other inhibitors like CTLA-4 and PD-1 are expressed on activated T cells.

Preclinically, KVA12123 has shown single-agent tumor growth inhibition, as well as when given in combination with PD-1 inhibitors. The use of KVA12123 drives an integrated innate and adaptive antitumor response in the MB49 preclinical model. KVA12123 was also well tolerated with no cytokine release syndrome (CRS)-associated signals observed. There were also no treatment-related adverse events, mortality, or overt clinical signs of weight loss seen in preclinical models.

According to data from the first 3 cleared monotherapy cohorts of the VISTA-101 trial (NCT05708950), KVA12123 was safe and well tolerated at doses of 3, 10, and 30 mg in patients with advanced solid tumors. Here, no dose-limiting toxicities were observed, and there was also no evidence of CRS-associated toxicities.

Administration of KVA12123 at the 30 mg dose level achieved >90% VISTA receptor occupancy. There was also greater than dose-proportional increase in drug exposure across all the doses evaluated in the trial.

"We have made noteworthy progress with the trial, and the data seen to date have demonstrated KVA12123 has been well tolerated with no dose limiting toxicities and no cytokine release syndrome. We are very pleased to resume enrollment for VISTA-101 and are focused on the successful execution and working towards completing enrollment which we expect to do by the end of 2024," said Thierry Guillaudeux, chief scientific officer of Kineta, in a press release.

About the VISTA-101 Trial

KVA12123 as a twice-weekly infusion is being assessed in the open-label, multicenter, dose-escalation and dose-expansion, phase 1/2 VISTA-101 trial.³ Investigators are evaluating the safety, tolerability, pharmacokinetics (PK), immunogenicity, and tumor response of KVA12123 as a monotherapy and in combination with pembrolizumab.

Enrollment in the trial is open to patients 18 years or older with a histologically or cytologically confirmed, locally advanced or metastatic solid tumor that has progressed or was not responsive to standard-of-care therapy. Patients are required to have an expected survival of ≥16 weeks, measurable disease, an ECOG performance status score of 0 or 1, adequate organ function, and normal thyroid function or hypothyroid with stable supplementation.

In the phase 1, dose-escalation portion of the study, up to 60 patients with advanced solid tumors will be enrolled. Phase 2, the dose-expansion portion of the study, will include patients with non–small cell lung cancer, head and neck cancer, ovarian cancer, colorectal cancer, and renal cell carcinoma, among others.

The drug is infused in patients every 2 weeks, and the first 3 cohorts of the study have been cleared with 3 mg, 10 mg, and 30 mg.

Type and frequency of adverse events and determining the maximum-tolerated dose, serve as the primary end points of the study, and secondary end points include PK and investigator assessment of radiographic imaging according to iRECIST, including patients with progressive disease, stable disease, partial response, and complete response.

REFERENCES:

1. TuHURA Biosciences and Kintara Therapeutics announce Kineta Inc. reopens enrollment for VISTA-101 clinical trial evaluating KVA12123 in patients with advanced solid tumor cancer. News release. TuHURA Biosciences, Inc. August 19, 2024. Accessed August 19, 2024. https://tinyurl.com/3sf57n78

2. ElTanbouly MA, Zhao Y, Nowak E, et al. VISTA is a checkpoint regulator for naïve T cell quiescence and peripheral tolerance. Science. 2020;367(6475):eaay0524. doi:10.1126/science.aay0524

3. A clinical trial of KVA12123 treatment alone and in combination with pembrolizumab on advanced solid tumors (VISTA-101). ClinicalTrials.gov. Updated July 13, 2023. Accessed August 19, 2024. https://tinyurl.com/2wd9u9b9