Dosing begins in ccRCC cohort of study assessing KO-2806

The first patient has been dosed with the next-generation farnesyl transferase inhibitor (FTI) KO-2806 in combination with cabozantinib (Cabometyx) as part of the clear cell renal cell carcinoma (ccRCC) cohort in the phase 1 portion of the FIT-001 trial (NCT06026410), announced Kura Oncology, the developer of the therapy, in a news release.¹

The primary outcome measures for the study are the rate of dose-limiting toxicities, adverse events, and the overall response rate per RECIST v1.1.

“Dosing of the first patient in combination in our phase 1 trial of KO-2806 marks a significant milestone for our next-generation FTI program,” said Stephen Dale, MD, Chief Medical Officer of Kura Oncology, in the news release.1 “This innovative, first-in-human trial builds upon our leadership position in the development of FTIs as well as a growing body of preclinical data demonstrating that combining KO-2806 with certain tyrosine kinase inhibitors, including cabozantinib, has the potential to address mechanisms of innate and adaptive resistance of targeted therapies, while driving tumor regressions and enhancing both duration and depth of antitumor response in preclinical models of ccRCC.”

Overall, the FIT-001 trial is assessing the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of KO-2806 as a monotherapy and in combination with targeted therapies in patients with advanced solid tumors, including ccRCC. The trial began with the dosing of the first patient in the monotherapy dose escalation portion of the trial in October 2023.²

Now, the combination therapy portion of the trial has begun by dosing patients with KO-2806 plus cabozantinib in ccRCC. According to Kura Oncology, the study will begin dosing KO-2806 in combination with adagrasib (Krazati) in patients with KRASG12C-mutant non-small cell lung cancer next quarter. The dose escalation study of KO-2806 as a monotherapy will continue in parallel to the combination therapy cohorts.

In total, the open-label, multicenter study plans to enroll 270 adult patients across several advanced solid tumor types. Participants will be treated across clinical trial sites in the US. In the ccRCC arm, patients must have received at least 1 prior systemic therapy with immunotherapy-based treatment for locally advanced or metastatic ccRCC to be enrolled in the study.³

All patients included in the study must have histologically or cytologically confirmed advanced solid tumors, measurable disease by RECIST v1.1, a Karnofsky performance status of 70 or higher with no clinically significant deterioration within the prior 2 weeks, and acceptable liver, renal, endocrine, and hematologic function.

Patients will be excluded from the study if they are receiving ongoing treatment with certain anticancer agents, have had prior treatment with an FTI or HRAS inhibitor, had major surgery within 28 days of the first study dose, have spinal cord compression, leptomeningeal disease, or clinically active central nervous system metastases, or have developed other invasive malignancies within 2 years. Additionally, patients must not have any presence of toxicity from prior therapy, have no active or prior documented autoimmune or inflammatory disorders within the prior 5 years, have no active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy, have impaired gastrointestinal (GI) function or GI disease, or demonstrate inadequate cardiac and/or vascular function.

The primary outcome measures for the study are the rate of dose-limiting toxicities, adverse events, and the overall response rate per RECIST v1.1. Secondary outcome measures include objective response rate, duration of response, progression-free survival, and overall survival.

Dale added in the news release,¹ “With this achievement, we are now one step closer to realizing our vision for broad application of KO-2806 as an ideal combination partner to drive enhanced antitumor activity and address mechanisms of innate and adaptive resistance to targeted therapies.”

Primary and final completion of the FIT-001 study is expected in 2027.

References

1. Kura Oncology reports first patient dosed in trial of KO-2806 plus cabozantinib in renal cell carcinoma. News release. Kura Oncology. Published online and accessed March 6, 2024. https://www.globenewswire.com/news-release/2024/03/06/2841290/35186/en/Kura-Oncology-Reports-First-Patient-Dosed-in-Trial-of-KO-2806-Plus-Cabozantinib-in-Renal-Cell-Carcinoma.html

2. Kura Oncology announces first patient dosed in FIT-001 trial of next-generation farnesyl transferase inhibitor KO-2806. News release. Kura Oncology. October 19, 2023. Accessed March 6, 2024. https://ir.kuraoncology.com/news-releases/news-release-details/kura-oncology-announces-first-patient-dosed-fit-001-trial-next

3. KO-2806 monotherapy and combination therapies in advanced solid tumors (FIT-001). ClinicalTrials.gov. Last updated November 22, 2023. Accessed March 6, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT06026410