Study launching of tivozanib plus novel HIF2α-inhibitor in kidney cancer

A phase 2 study launching this year is exploring the combination of the VEGFR tyrosine kinase inhibitor tivozanib (Fotivda) and the investigational HIF2α-inhibitor NKT2152 in patients with relapsed/refractory clear cell renal cell carcinoma (RCC).1

“Preclinical and early clinical data have demonstrated enhanced anti-tumor activity by the combination of HIF2α and VEGFR inhibition,” Zhenhai Gao, PhD, co-founder, president, and chief executive officer of NiKang, the developer of NKT2152 stated in a news release.

HIF2α inhibitors are a burgeoning targeted therapy class in RCC, highlighted by the 2021 FDA approval of the HIF2α-inhibitor belzutifan (Welireg) for patients with von Hippel-Lindau (VHL) disease–associated RCC.2 The approval was supported by data from phase 2 Study 004, in which belzutifan induced an objective response rate of 49% (n = 30) among 61 patients with VHL-associated RCC.

Tivozanib was approved by the FDA in 2021 for the treatment of adult patients with relapsed or refractory advanced RCC who have received 2 or more prior systemic therapies.3 The approval was based on data from the phase 3 TIVO-3 trial. Results from the study presented during the 2020 ASCO Virtual Scientific Program4 showed that the tivozanib demonstrated a significant improvement in progression-free survival (PFS) compared with sorafenib (Nexavar), with similar overall survival (OS), in patients with highly relapsed/refractory metastatic RCC.

Results showed that the final hazard ratio (HR) for OS was 0.97 (P = .78). Moreover, an updated analysis of the data found that, with a median follow-up of 38 months for tivozanib and 40 months for sorafenib, the median OS was 16.4 months for tivozanib and 19.2 months for sorafenib. A subset analysis showed the greatest benefit was derived by the cohort of patients who previously received a checkpoint inhibitor and VEGF inhibitor, with an HR of 0.55, or 2 VEGF TKIs, with an HR of 0.57. Prior findings showed an increased median PFS for tivozanib when compared with sorafenib at 5.6 months versus 3.9 months, respectively (HR, 0.73; P = .016).

Commenting in the news release on the potential of tivozanib/NKT2152, Michael Bailey, president and chief executive officer of AVEO, the developer of tivozanib, stated, “The tivozanib and NKT2152 combination will build on the activity seen with VEGFR TKIs and HIF2α agents in clear cell RCC. We believe the best-in-class qualities of these two compounds provide a unique combination of efficacy and tolerability for patients with relapsed/refractory clear cell RCC as a doublet or, potentially in the future, as part of a triple combination.”


1.NiKang Therapeutics and AVEO Oncology Announce a Clinical Trial Collaboration and Supply Agreement to Evaluate the Combination of NKT2152, a HIF2α Inhibitor, and FOTIVDA® (tivozanib) for the Treatment of Advanced Clear Cell Renal Cell Carcinoma. Published online January 5, 2022. Accessed January 7, 2022.

2. FDA approves belzutifan for cancers associated with von Hippel-Lindau disease. Published online August 13, 2021. Accessed August 13, 2021.

3. AVEO Oncology Announces U.S. FDA Approval of FOTIVDA® (tivozanib) for the Treatment of Adult Patients with Relapsed or Refractory Advanced Renal Cell Carcinoma. Published online March 10, 2021. Accessed March 10, 2021.

4. Pal SK, Escudier B, Atkins MB, et al. TIVO-3: Final OS analysis of a phase III, randomized, controlled, multicenter, open-label study to compare tivozanib to sorafenib in subjects with metastatic renal cell carcinoma (RCC). Presented at: 2020 ASCO Virtual Program; May 27, 2020. Abstract 5062.