NKT2152 is a novel oral HIF-2α inhibitor in development for the treatment of advanced clear cell renal carcinoma (ccRCC) and other tumors. The drug is being studied in an ongoing Phase I/II trial (NCT05119335) investigating its safety, pharmacokinetics, pharmacodynamics, and clinical efficacy in patients with accRCC. Preliminary results with a data cut-off of February 20, 2024, were presented at ESMO 2024, highlighting the drug's potential and ongoing development.

With a median follow-up of 12 months, the NKT2152 trial showed that 40% of patients remained on treatment, while 14% discontinued due to adverse events. Among 81 patients assessed for efficacy, the confirmed objective response rate (ORR) was 24%, with a median progression-free survival (PFS) of 7.5 months. The median duration of response has not yet been reached. Notably, in a subset of 35 patients with no prior mTOR inhibitor use and a median of three prior lines of therapy, the ORR was 40%, and the median PFS of 9.4 months. 

Pharmacokinetics showed dose-linear and time-independent behavior, and erythropoietin suppression was observed across all dose levels. Overall, NKT2152 exhibited strong anti-tumor activity in heavily pretreated ccRCC patients, with a safety profile aligning with expectations for this class of drugs.

KOL insights

“ Belzutifan refractory disease in advanced RCC may represent an opportunity for NKT2512 Encouraging efficacy and safety in heavily pretreated patients”- Medical Oncologist

Conclusion 

The preliminary results from a Phase I/II study of NKT2152, presented at ESMO 2024, provide promising insights into its efficacy with a 24% ORR and a median PFS of 7.5 months in a heavily pretreated patient population. The safety profile is consistent with similar agents, highlighting NKT2152's potential as a valuable treatment option in this challenging cancer space.

The landscape of advanced RCC treatment is highly competitive, with several key players and therapies dominating the market. Merck’s WELIREG (belzutifan), another oral HIF-2α inhibitor that targets the same pathway in the RCC space has made a foothold in the RCC market, as the drug secured FDA approval in December 2023 for the treatment of adult patients with advanced RCC following PD-1/PD-L1 inhibitor and VEGF-TKI. With this approval, Merck marked the introduction of a new therapeutic class in RCC after nearly a decade. 

NKT2152’s preliminary results suggest it could become a valuable addition to the treatment armamentarium for advanced ccRCC.

For more insight into the patient's burden/epidemiology, treatment, and changing market landscape-related advancements, refer to the Renal Cell Carcinoma - Market Insight, Epidemiology and Market Forecast - 2032.