KEY TAKEAWAYS
- The phase 1 and 2 trial aimed to investigate the safety, pharmacokinetics, pharmacodynamics, and efficacy of NKT2152 in patients with accRCC.
- NKT2152 showed strong anti-tumor activity in patients with heavily pretreated accRCC, with a consistent safety profile.
NKT2152, a novel oral hypoxia-inducible factor 2α (HIF-2α) inhibitor, is being developed for treating advanced clear cell renal cell carcinoma (accRCC). HIF-2α plays a crucial role in tumour growth and progression, making it a promising therapeutic target.
In this ongoing Phase I/II trial, Eric Jonasch and the team aimed to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical efficacy of NKT2152 in patients with accRCC who have progressed on prior therapies.
The study enrolled adult patients with accRCC who had progressed on at least 1 prior therapy and were not eligible for standard treatment. Patients received NKT2152 in 8 dose-escalation cohorts (4 daily and 4 loading/maintenance regimens), followed by a randomized expansion at 2 selected dose levels. The study included PK analysis, development of a population PK-erythropoietin model, and an exploratory exposure-response analysis.
About 96 patients were enrolled in the study, with a median follow-up of 12 months. The confirmed ORR was 24%, and the mPFS was 7.5 months. Notably, in a subset of 35 patients who had not received prior mTOR inhibitors, the ORR was 40%, and the mPFS was 9.4 months. NKT2152 exhibited dose-linear and time-independent pharmacokinetics. EPO suppression was observed at all dose levels. The safety profile was consistent with this class of agents.
NKT2152 demonstrated robust anti-tumor activity in heavily pre-treated patients with accRCC, particularly those without prior mTOR inhibitor exposure. The safety profile was consistent with other agents in its class. Further research is ongoing to evaluate the full therapeutic potential of NKT2152 in treating accRCC.
The trial is sponsored by NiKang Therapeutics, Inc.
Source: https://cslide.ctimeetingtech.com/esmo2024/attendee/confcal/show/session/14
Clinical Trial: https://clinicaltrials.gov/study/NCT05119335
Jonasch E, McGregor BA, Msaouel P, et al. (2024). “NKT2152, a novel oral HIF-2α inhibitor, in participants (pts) with previously treated advanced clear cell renal carcinoma (accRCC): Preliminary results of a phase I/II study.” Presented at: ESMO Congress 2024; 2024; 1690O.
