Abstract
1690O 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
Annals of oncology, Vol.35(Supplement 2), pp.S1011-S1012
09/2024
DOI: 10.1016/j.annonc.2024.08.1783
Abstract
Background
NKT2152 is a novel oral HIF-2α inhibitor in development for the treatment of accRCC and other tumors. In an ongoing Phase 1/2 trial (NCT05119335), we investigated safety, pharmacokinetics (PK), pharmacodynamics and clinical efficacy in pts with accRCC.
Methods
Adult pts with accRCC not amenable to standard therapy, ECOG status of 0-2, and progression after ≥1 prior regimen received NKT2152 in 8 dose escalation (DE) cohorts: 4 daily and 4 loading/maintenance regimens, followed by a randomized expansion (Exp) at two selected dose levels. A population PK - erythropoietin (EPO) model was developed, and an exploratory exposure-response analysis was conducted. We report a preliminary analysis with a data cut-off of 20Feb2024.
Results
96 pts (71 DE, 25 Exp) were enrolled: IMDC risk: 56% intermediate/39% poor; 4+ prior lines: 37%; prior mTOR inhibitor (mTORi): 32%, prior VEGFR-TKI: 93%, prior anti PD-(L)1: 98%. Overall, median follow-up was 12 months (range: 0.23-27), 40% of pts had ongoing treatment and 14% discontinued the study for an adverse event (AE). The maximum tolerated dose was not reached. In 81 efficacy evaluable pts, the confirmed objective response rate by RECIST 1.1 (ORR) was 24% (95% confidence interval: 15-34%) with median progression-free survival (mPFS) of 7.5 months (3.7-13). Median duration of response was not reached. In a subset of 35 evaluable pts with no prior mTORi (median prior lines: 3) enrolled at least 9 months prior to the cut-off, ORR was 40% (24-58%) and mPFS was 9.4 months (5.5-14). PK was dose linear and time independent. EPO suppression was observed at all dose levels (Imax = 0.75, IC50 = 63 ng/mL).
Conclusions
NKT2152 demonstrated robust anti-tumor activity in heavily pretreated accRCC pts. The safety profile was consistent with this class of agent.
Details
- Title: Subtitle
- 1690O 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
- Creators
- E. Jonasch - The University of Texas MD Anderson Cancer CenterB.A. McGregor - Dana-Farber Cancer InstituteP. Msaouel - The University of Texas MD Anderson Cancer CenterT. Logan - Indiana UniversityE.T. Hall - University of WashingtonM.A. Bilen - Winship Cancer InstituteG.S. Falchook - Sarah Cannon Research InstituteB. Shuch - University of California, Los AngelesY. Zakharia - University of IowaR. Hauke - Nebraska Cancer SpecialistsM. Gordon - HonorHealthA-R. Naqash - OU HealthC.W. Ryan - Oregon Health & Science UniversityR. Srinivasan - National Cancer InstituteJ. Xiao - Clinical Pharmacology, NiKang Therapeutics, Inc., Wilmington, DE, USAW. Sun - Clinical Research, NiKang Therapeutics, Inc., Wilmington, DE, USAM. Esguerra - Clinical Research, NiKang Therapeutics, Inc., Wilmington, DE, USAG. Lu - Clinical Research, NiKang Therapeutics, Inc., Wilmington, DE, USAJ. Lager - Medical Oncology, NiKang Therapeutics, Inc., Wilmington, DE, USAT.K. Choueiri - Dana-Farber Cancer Institute
- Resource Type
- Abstract
- Publication Details
- Annals of oncology, Vol.35(Supplement 2), pp.S1011-S1012
- DOI
- 10.1016/j.annonc.2024.08.1783
- ISSN
- 0923-7534
- Publisher
- Elsevier Ltd
- Language
- English
- Date published
- 09/2024
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984708955302771
Metrics
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