On November 6, 2023 Kineta, Inc. (Nasdaq: KA), a clinical-stage biotechnology company focused on the development of novel immunotherapies in oncology that address cancer immune resistance, reported the presentation of new positive data from its ongoing VISTA-101 Phase 1/2 clinical trial evaluating KVA12123, the company’s VISTA blocking immunotherapy, in patients with advanced solid tumors at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 38th Annual Meeting (Press release, Kineta, NOV 6, 2023, View Source;utm_medium=rss&utm_campaign=kineta-unveils-positive-new-data-from-vista-101-clinical-trial-of-kva12123-at-the-society-for-immunotherapy-of-cancers-sitc-38th-annual-meeting [SID1234637035]). Thierry Guillaudeux, Ph.D., Chief Scientific Officer of Kineta, presented the company’s poster unveiling the new clinical data.

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"We are excited to unveil these promising findings from our ongoing VISTA-101 clinical trial. VISTA blocking immunotherapy KVA12123 has performed remarkably well in demonstrating excellent safety and tolerability in the clinic. Notably, the pharmacokinetic data and biomarker assessments demonstrate the drug’s potential efficacy and confirm its mechanism of action," said Shawn Iadonato, Ph.D., Chief Executive Officer of Kineta. "We continue to advance KVA12123 to the higher monotherapy dose levels, as well as evaluate it in combination with pembrolizumab, where we recently announced the first patient dosed. Kineta is committed to advancing KVA12123 as a potential new immunotherapy for cancer patients in need of new treatment options."

The Phase 1/2 VISTA-101 trial (NCT05708950) enrolled 11 patients with advanced solid tumors in the first three monotherapy dose-escalation cohorts, where subjects received either 3, 10 or 30 mg of KVA12123 by intravenous (IV) infusion every two weeks. Primary objectives of the Phase 1/2 study are to evaluate the safety and tolerability of KVA12123 and to determine the recommended Phase 2 dose (RP2D). Patients enrolled in the study were heavily pretreated with multiple prior lines of therapy including chemotherapy, radiation and immunotherapy. Additional monotherapy and initial combination therapy data are anticipated in the second quarter of 2024.

Key highlights from the poster presentation:

Safety
Eleven patients were dosed and cleared the first three monotherapy cohorts. KVA12123 was well tolerated at all doses and no dose limiting toxicities (DLT) were observed. All KVA12123 treatment emergent adverse events were grades 1-2. Furthermore, no evidence of cytokine release syndrome (CRS) or associated cytokines including IL-6, TNFα & IL-10 were detected at any of the dose levels.

Pharmacokinetics and VISTA Receptor Occupancy (RO)
KVA12123 exhibited a greater than dose-proportional pharmacokinetic profile in drug exposure across all evaluated doses, consistent with target-mediated drug disposition at lower doses. To guide the RP2D decision, Kineta developed a proprietary assay to evaluate VISTA RO on immune cells from patients treated with KVA12123. KVA12123 achieved a greater than 90% VISTA RO at the 30 mg dose indicating that KVA12123 may be approaching an optimal clinical dose.

Biomarkers
KVA12123 demonstrated dose-proportional on-target biomarker immune responses involved in anti-tumor activity. KVA12123 demonstrated significant efficacy-related cytokine induction of CXCL10, MCP1, MIP1α and MIP1β, which are involved in immune cell activation and recruitment to the tumor microenvironment. Additionally, increases in anti-tumor immune cell subpopulations including nonclassical monocytes, NK cells, CD4+ T cells and CD8+ T cells were observed during treatment. Changes in these key biomarkers and immune cell populations are indicative of the anti-tumor effects of blocking VISTA.

The poster presentation is available for viewing under Publications in the KVA12123 section of the company’s website at www.kinetabio.com .

SITC Presentation Details:
Title: VISTA-101 – A phase 1/2 clinical trial of KVA12123, an engineered IgG1 targeting VISTA, alone and in combination with pembrolizumab in advanced solid tumors
Abstract Number: 780
Date / Time: Saturday, November 4 at 9:00 A.M. – 7:00 P.M. Pacific Time
Location: Exhibit Halls A and B1 – San Diego Convention Center

Kineta is advancing the VISTA-101 trial to higher monotherapy dose levels and recently initiated Part B of the study evaluating KVA12123 in combination with pembrolizumab. Additional monotherapy safety and efficacy data and combination therapy clinical data are anticipated in the second quarter of 2024.