On October 3, 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 an update on its ongoing Phase 1/2 clinical trial evaluating KVA12123 in patients with advanced solid tumors (Press release, Kineta, OCT 3, 2023, View Source;utm_medium=rss&utm_campaign=kineta-announces-positive-kva12123-monotherapy-safety-and-biomarker-data-from-its-ongoing-phase-1-2-vista-101-clinical-trial [SID1234635598]). KVA12123, Kineta’s immuno-oncology drug targeting VISTA, cleared the first three monotherapy dose levels and was well tolerated with no dose limiting toxicities (DLT) or cytokine related adverse events observed. Additionally, KVA12123 exhibited a greater than dose-proportional pharmacokinetic profile achieving greater than 90% VISTA receptor occupancy (RO) across patients in the 30 mg dosing cohort.
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"We are very pleased with the progress of our Phase 1/2 clinical trial, showing very compelling initial safety and pharmacokinetic data for KVA12123, which we believe significantly de-risks VISTA as a novel drug target," said Shawn Iadonato, Ph.D., Chief Executive Officer of Kineta. "We appreciate the patients and healthcare providers that are participating in this important study, and we look forward to further evaluating KVA12123’s potential for treating patients with advanced solid tumors."
The 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.
Safety Profile
In the first three monotherapy cohorts, KVA12123 was well tolerated at all doses and no DLTs were observed. Furthermore, as KVA12123 was engineered to mitigate adverse events associated with cytokine release syndrome (CRS), the study is closely monitoring proinflammatory cytokines that are associated with CRS (IL-6 and TNFα) in the Phase 1 portion of the study. No evidence of CRS or proinflammatory cytokine induction have been observed at any dose level with KVA12123 in the initial cohorts.
Pharmacokinetics and Receptor Occupancy
To guide the RP2D decision, Kineta developed a proprietary assay to evaluate VISTA RO on immune cells from patients treated with KVA12123. Greater than 90% VISTA RO was achieved at the 30 mg dose. Furthermore, pharmacokinetic analyses demonstrated a greater than dose-proportional increase in drug exposure across all evaluated doses, consistent with target-mediated drug disposition at lower doses.
"We are thrilled to see greater than 90% VISTA receptor occupancy in patients treated with 30 mg dose. This indicates that we can saturate the target without dose limiting toxicities and are close to achieving an optimal dose for KVA12123," said Thierry Guillaudeux, Ph.D., Chief Scientific Officer of Kineta. "We believe that KVA12123 has the potential to become an important new immunotherapy for the many patients with cancer in need of new therapeutic options."
Competitive therapies targeting VISTA have demonstrated either poor monotherapy anti-tumor activity in preclinical models or induction of CRS in human clinical trials. Through the combination of unique epitope binding and an optimized IgG1 Fc region, KVA12123 demonstrates strong monotherapy tumor growth inhibition in preclinical models without evidence of CRS in clinical trial participants. KVA12123 effectively de-risks the VISTA target and provides a novel approach to address immune suppression in the TME with a mechanism of action that is differentiated and complementary with T cell focused therapies. KVA12123 may be an effective immunotherapy for many types of cancer including non-small cell lung (NSCLC), colorectal, renal cell carcinoma, head and neck, and ovarian cancer.
The company will continue escalating monotherapy dose cohorts of KVA12123 in Part A and initiate Part B of the study to evaluate KVA12123 in combination with pembrolizumab. Initial monotherapy efficacy data are anticipated in Q4 2023 and will be presented, along with safety data, at an upcoming medical conference.