Study progresses of KVA12123 in solid tumors, including renal cell carcinoma

The phase 1/2 VISTA-101 trial (NCT05708950), exploring KVA12123 as a monotherapy and in combination with pembrolizumab (Keytruda) in patients with advanced solid tumors, including renal cell carcinoma (RCC), continues to progress in both the monotherapy and combination arms.

Kineta also announced that they have suspended enrollment in the VISTA-101 study.

According to a news release from Kineta, the developer of the VISTA blocking immunotherapy, the study has dosed all patients at dose level 5 of 6 in the monotherapy arm and all patients at the dose level 2 of 4 in the combination arm.¹

“We are pleased with the progress of the study, the initial clinical response data, and the durability of patient benefit emerging from the study. We continue to be encouraged by the safety profile of KVA12123, supporting advancement to higher doses,” said Thierry Guillaudeux, PhD, Chief Scientific Officer of Kineta, in the news release.¹ “KVA12123 has a best-in-class potential that may offer patients a novel approach to address immunosuppression in the tumor microenvironment to better manage solid tumor cancers.”

Overall, KVA12123 was well-tolerated with no dose-limiting toxicities or cytokine-related adverse events at any dose level assessed so far.

In total, the monotherapy dose escalation arm has enrolled 21 patients, with 12 having received at least 1 baseline and 1 follow-up scan. Among those 12 patients, 9 achieved the best overall response (BOR) of stable disease with a mean duration of 15 weeks. Overall, 9 patients remain on-treatment in this arm.

In the combination arm, the study has enrolled 9 patients, 3 of whom received at least 1 baseline and 1 follow-up scan. Among those 3 patients, the BOR with KVA12123 plus pembrolizumab was observed in 2 patients, including 1 patient with RCC who failed prior checkpoint-inhibitor therapy and 1 patient with PD-L1 negative mucoepidermoid carcinoma. The patient with RCC achieved stable disease with a 24% reduction in target lesions, and the patient with mucoepidermoid carcinoma achieved a partial response with a 54% reduction in target lesions and a complete response in non-target lesions. Overall, 8 patients remain on treatment in this arm.

Further, treatment with KVA12123 has led to dose-dependent induction of on-target pro-inflammatory cytokines and chemokines as well as dose-dependent increases in non-classical monocytes, CD4+ and CD8+ T cells, and NK cells.

Overall, the open-label, multicenter VISTA-101 study is assessing the safety, tolerability, pharmacokinetics, immunogenicity, and tumor response of KVA12123 alone and in combination with pembrolizumab in patients with advanced solid tumors. The study will be conducted in 4 parts, with part A and B focused on dose escalation of KVA12123 as a single agent and in combination and parts C and D focused on dose expansion of KVA12123 as a single agent and in combination. The objective of parts A and B are to determine a recommended phase 2 dose of the therapy for the next phase of study.²

Patients included in the monotherapy cohorts will receive KVA12123 at a dose level ranging from 3 mg to 300 mg once every 2 weeks. Those in the combination therapy cohorts will receive KVA12123 at a dose level ranging from 30 mg to 100 mg once every 2 weeks, in addition to 400 mg pembrolizumab every 6 weeks.

In the news release,¹ Kineta also announced that they have suspended enrollment in the VISTA-101 study and will not be recruiting patients into the sixth monotherapy cohort nor to the third combination therapy cohort due to funding obligations of their investors not being met. Those currently enrolled in the study will be permitted to continue on study treatment.

References

1. KVA12123 clears additional cohorts in monotherapy and in combination therapy arms in the phase 1/2 VISTA-101 clinical trial; initial clinical response data reported. News release. Kineta, Inc. March 12, 2024. Accessed March 15, 2024. https://www.globenewswire.com/news-release/2024/03/12/2844483/0/en/KVA12123-Clears-Additional-Cohorts-in-Monotherapy-and-in-Combination-Therapy-Arms-in-the-Phase-1-2-VISTA-101-Clinical-Trial-Initial-Clinical-Response-Data-Reported.html

2. A clinical trial of KVA12123 treatment alone and in combination with pembrolizumab in advanced solid tumors (VISTA-101). ClinicalTrials.gov. Last updated July 13, 2023. Accessed March 15, 2024. https://clinicaltrials.gov/study/NCT05708950