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

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). Table: 1690O

Treatment-emergent AE (TEAE)

Conclusions

NKT2152 demonstrated robust anti-tumor activity in heavily pretreated accRCC pts. The safety profile was consistent with this class of agent.

Clinical trial identification

NCT05119335.

Editorial acknowledgement

Medical writing support was provided by Amy C. Porter, PhD, ISMPP CMPP^TM of Certara, funded by NiKang Therapeutics, Inc.

Legal entity responsible for the study

NiKang Therapeutics, Inc.

Funding

NiKang Therapeutics, Inc.

Disclosure

E. Jonasch: Financial Interests, Personal, Advisory Board: Aveo, Eisai, Exelixis, GSK, Ipsen, Merck, NiKang, Telix, Novartis; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Institutional, Trial Chair, Clinical trial: Aveo; Financial Interests, Institutional, Trial Chair, Clinical Trial: Corvus, Telix; Financial Interests, Institutional, Local PI, Clinical Trial: AbbVie, ProFoundBio; Financial Interests, Institutional, Research Grant, Correlative Research: Arrowhead; Financial Interests, Institutional, Trial Chair, Clinical trials: Merck; Financial Interests, Institutional, Steering Committee Member, Clinical Trial: NiKang; Non-Financial Interests, Leadership Role, Vice Chair, NCCN Kidney Cancer Guidelines: NCCN; Non-Financial Interests, Member of Board of Directors, Board member International Kidney Cancer Coalition: IKCC. B.A. McGregor: Financial Interests, Personal, Advisory Board: Exelixis, BMS, Dendreon, Seagen, Astellas, Eisai, Pfizer, Gilead, Arcus, Loxo/Lily; Financial Interests, Personal, Invited Speaker: EMD Serono, Seagen; Financial Interests, Institutional, Trial Chair: Pfizer, Exelixis, Exelixis, BMS, Gilead; Financial Interests, Institutional, Local PI: Calithera, Seagen, Aveo; Non-Financial Interests, Member: ASCO. P. Msaouel: Financial Interests, Personal, Advisory Board: Mirati Therapeutics, BMS, Exelixis; Financial Interests, Personal, Advisory Role: Axiom Healthcare, Exelixius, Pfizer; Financial Interests, Personal, Advisory Role, Non-branded educational programs: DAVA oncology; Financial Interests, Personal, Membership or affiliation, Medical Steering Committee member: Kidney Cancer Association; Financial Interests, Personal, Advisory Board, Kidney Cancer Scientific Advisory Board: KCCure; Financial Interests, Personal and Institutional, Funding: Takeda, BMS, Mirati Therapeutics, Gateway for Cancer Research. T. Logan: Financial Interests, Institutional, Funding: Abbott, Abraxis, Acceleron, Amgen, Argos, AstraZeneca, Aveo, Biovex, BMS, Eisai, Lilly, GSK, Immatics, Roche, Merck, Novartis, Pfizer, Synta, Threshold, Millenium, Tracon, Cerulean, EMD Serono, Prometheus, Peloton, Iovance, MedImmune, Dynavax, NiKang, Macrogenics; Financial Interests, Personal, Advisory Board: Prometheus. E.T. Hall: Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Institutional, Funding: Treatment Technologies and Insights, Neoleukin Therapeutics, ImCheck Therapeutics, Nektar, Replimune, Checkmate Pharmaceuticals, BMS, NiKang, Gilead, Pfizer. M.A. Bilen: Financial Interests, Personal, Advisory Board: Exelixis, Bayer, BMS, Eisai, Pfizer, AstraZeneca, Janssen, Calithera Biosciences, Nektar, EMD Serono, Seagen, Sanofi; Financial Interests, Institutional, Local PI: Merck, Xencor, Bayer, Bristol Myers Squibb, Genentech/Roche, Seagen, Incyte, Nektar, AstraZeneca, Tricon Pharmaceuticals, Genome & Company, AAA, Peloton Therapeutics, Pfizer. G.S. Falchook: Financial Interests, Institutional, Advisory Board, 2018: FujiFilm; Financial Interests, Institutional, Advisory Board, 7/24/2020, 9/17/2021: Silicon; Financial Interests, Institutional, Advisory Board, 3/10/21: Navire; Financial Interests, Institutional, Advisory Board, 4/22/21: Turning Point; Financial Interests, Institutional, Advisory Board, 10/2/21: Predicine; Financial Interests, Institutional, Advisory Board, 10/26/21: Inspirna; Financial Interests, Institutional, Advisory Board, 10/28/21: Regeneron; Financial Interests, Personal, Advisory Board, 6/2010, 3/2011: EMD Serono; Financial Interests, Institutional, Advisory Board, 1/18/22 and 8/17/22: Jubilant; Financial Interests, Institutional, Advisory Board, 6/4/22: BostonGene; Financial Interests, Institutional, Advisory Board, 9/30/22: AbbVie; Financial Interests, Personal, Invited Speaker, 2019: Total Health Conferencing; Financial Interests, Personal, Invited Speaker, 2020: Rocky Mountain Oncology Society; Financial Interests, Personal, Other, Travel, for work and/or research related to institution, 2015: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel, for work and/or research related to institution, 2011, 2012, 2013: EMD Serono; Financial Interests, Personal, Other, Travel, to present research at a conference (Cholangiocarcinoma Foundation meeting), 2018: Fujifilm; Financial Interests, Personal, Other, Travel, to present research at a conference (ESGO), 2013: Millennium; Financial Interests, Personal, Other, Travel, for work and/or research related to institution, at least once yearly: Sarah Cannon Research Institute (employer); Financial Interests, Personal, Other, Travel, to present research at a conference (WCLC), 2022: Amgen; Financial Interests, Personal, Other, Travel, to present research at a conference (ESMO), 2022: Synthorx / Sanofi; Financial Interests, Institutional, Advisory Board, Scientific advisory board 11/18/22: Teon Therapeutics; Financial Interests, Institutional, Advisory Board, 12/8/22: Merck; Financial Interests, Personal, Invited Speaker, CME presentation about NSCLC and thyroid cancer, 2/20/24: Clinical Care Options; Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Institutional, Local PI, Unknown end date, before 1/2021: 3-V Biosciences, ARMO/Eli Lilly, Celldex, DelMar, eFFECTOR, Kolltan, miRNA Therapeutics, OncoMed, Precision Oncology, Strategia; Financial Interests, Institutional, Local PI, 12/2019 - 6/2023: Abbisko; Financial Interests, Institutional, Local PI, ending 4/2019: Abbvie; Financial Interests, Institutional, Local PI, 8/2021 - present: ABL Bio; Financial Interests, Institutional, Local PI, 12/2021 - 8/2023: Accutar; Financial Interests, Institutional, Local PI: Aileron, Amgen, AstraZeneca, BeiGene, Fujifilm, Jacobio, Jounce, Loxo/Bayer, Merck, Regeneron, Rgenix, Takeda; Financial Interests, Institutional, Local PI, ending 6/2014: American Society of Clinical Oncology, Celgene, EMD Serono, Genmab, MedImmune, National Institutes of Health, Oncothyreon, U.T. 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TeneoBio was purchased by Amgen: Teneobio; Financial Interests, Institutional, Local PI, ending 1/2020: Tocagen; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial. 05/2022-11/2022: Metabomed; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial. 6/2022 - present: Agenus; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial. 06/2022 - present: Tallac; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial. 7/2022 - present: Zhuhai Yufan, Mirati; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial. 10/2022 - present: Immunitas, Jazz Pharmaceuticals; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial. 11/2022 - present: Bayer; Financial Interests, Institutional, Local PI, 1/2019 - present: ADC Therapeutics; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial. 3/2023 - present: Kineta, Roche; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial. 03/2023 - present: NGM Biopharmaceuticals; Financial Interests, Institutional, Local PI, 4/2023 - present: Tarus; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial. 05/2023 - present: Pyxis; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial. 06/2023 - present: Harbour BioMed, Centessa Pharmaceuticals; Financial Interests, Institutional, Local PI, 07/2023 - present: IDEAYA, Tango Therapeutics; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial. 08/2023 - present: Biomea Fusion; Financial Interests, Institutional, Local PI, 09/2023 - present: Conjupro Biotherapeutics; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial. 09/2023 - present: Phanes Therapeutics; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial. 9/2023 - present: Sarah Cannon Development Innovations; Financial Interests, Institutional, Local PI, 10/20/23 - present: Nuvectis Pharma; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial. 1/20/24 - present: Kura Oncology; Financial Interests, Institutional, Local PI, 1/2024 - present: Eikon Therapeutics. B. Shuch: Financial Interests, Personal, Advisory Role: Merck, Telix, Johnson & Johnson, Veracyte; Financial Interests, Institutional, Funding: Telix, Kidney Cancer Association, KureIT Foundation, DOD. Y. Zakharia: Financial Interests, Personal, Advisory Board: BMS, Amgen, Roche Diagnostics, Novartis, Janssen, Eisai, Exelixis, Castle Bioscience, Genzyme, AstraZeneca, Array, Bayer, Pfizer, Clovis, EMD Serono, Myovant; Financial Interests, Institutional, Funding: Pfizer, Exelixis, Eisai; Financial Interests, Personal, Advisory Role: Pfizer, Janssen, Novartis. R. Hauke: Financial Interests, Personal, Advisory Board: Novartis. M. Gordon: Financial Interests, Personal, Advisory Role: Imaging Endpoints, Cardinal Helathcare, Medtronics, Onquality, Pfizer, Qualigen, Springworks Tx, Viracta; Financial Interests, Personal, Other, Co-owner: Sphinx Health Solutions; Financial Interests, Institutional, Funding: Agenus, BeiGene, DynamiCure, Fore, Plexxicon, Genentech, Roche, Nikang, Novartis, Nimbus, OncoResponse, Pyxis Oncology, Riboscience, SQZ Biotech, Syndax, Redhill Bio, Veru. A. Naqash: Financial Interests, Personal, Other, Social Media Editor and Consultant: JCO Precision Oncology; Financial Interests, Institutional, Local PI: Loxo, Surface Oncology, ADC Therapeutics, IGM Biosciences, Nikang Therapeutics, Inspirna, Revolution Medicine, Jacobio, Pionyr, Jazz, NGM; Financial Interests, Institutional, Coordinating PI: EMD Serono, Aravive; Non-Financial Interests, Social Media Consultant and Scientific Committee Member: ASCO; Non-Financial Interests, Educational Activity: OncLive; Non-Financial Interests, Leadership Role, Scientific Committee Co Chair: ORIEN; Non-Financial Interests, Leadership Role, Early Career Scientist Committee: SITC. C.W. Ryan: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, GSK, Pfizer; Financial Interests, Institutional, Local PI: Ayala, Bristol Myers Squib, Daiichi-Sankyo, Deciphera, Exelixis, Genentech, Novartis, Karyopharm, Merck, Nektar, Pfizer, Xynomic, Rain Therapeutics, PTC Therapeutics, NiKang Therapeutics, Shasqi Therapeutics, PF Argentum IP Holdings, LLC. R. Srinivasan: Financial Interests, Institutional, Local PI, Provided drugs to conduct the studies and funds to NCI to partially cover the costs of conducting the study at the NIH: Nikang, Allogene, Merck/Peloton; Financial Interests, Institutional, Coordinating PI, Will provide investigational agents for an investigator-initiated study under a CRADA with the NCI: Genentech, Novartis, Pfizer; Non-Financial Interests, Advisory Role, Nikang KOL Steering Committee participation: Nikang. J. Xiao, W. Sun, M. Esguerra: Financial Interests, Personal, Full or part-time Employment: NiKang. G. Lu: Financial Interests, Personal, Full or part-time Employment: NiKang; Financial Interests, Personal, Other, Owner: Lucier Pharmaceuticals; Financial Interests, Personal, Other, Owns stock: Chimerix. J. Lager: Financial Interests, Personal, Full or part-time Employment, Shareholder: NiKang. T.K. Choueiri: Financial Interests, Personal, Advisory Board, Advice on GU/RCC drugs: BMS, Pfizer, Merck, Exelixis, AstraZeneca; Financial Interests, Personal, Advisory Board, Advice on Onc drugs: Lilly, EMD Serono, Infinity; Financial Interests, Personal, Advisory Board, Advice on RCC drug: Calithera; Financial Interests, Personal, Invited Speaker, RCC drug: Ipsen; Financial Interests, Personal, Advisory Board, Advice on GU Onc drugs: Surface Oncology; Financial Interests, Personal, Other, Consultant on onc drugs: Analysis Group; Financial Interests, Personal, Invited Speaker, CME, ww2.peerview.com: Peerview; Financial Interests, Personal, Invited Speaker, CME, gotoper.com: PER; Financial Interests, Personal, Invited Speaker, CME, researchtopractice.com: ResearchToPractice; Financial Interests, Personal, Invited Speaker, National Association of Managed Care: NAMC; Financial Interests, Personal, Invited Speaker, ASCO-related event: ASCO-SITC; Financial Interests, Personal, Other, Grant review to Orien Network ($400): ORIEN; Financial Interests, Personal, Advisory Board, Advising oncology strategy: Aptitude Health; Financial Interests, Personal, Invited Speaker, Best of ASCO19 talk: Advent health; Financial Interests, Personal, Invited Speaker, Best of ESMO20 talk ($1000): UAE Society of Onc; Financial Interests, Personal, Invited Speaker, CME, mjhlifesciences.com (OncLive): MJH life sciences; Financial Interests, Personal, Invited Speaker, Grand Rounds: MDACC; Financial Interests, Personal, Invited Speaker, RCC webinar: Cancernet; Financial Interests, Personal, Invited Speaker, CME, Kidney Cancer Association ($1300): France Foundation; Financial Interests, Personal, Invited Speaker, CME, RCC: Springer, WebMed; Financial Interests, Personal, Invited Speaker, CME, ImmunoOncology in RCC: ASiM, CE; Financial Interests, Personal, Invited Speaker, CME, PodCast in RCC ($500.00): Caribou Publishing; Financial Interests, Personal, Invited Speaker, Reimbursement ($432.00): Kidney Cancer Association; Financial Interests, Personal, Other, member of the DSMB for clinical trial: Aravive; 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Financial Interests, Personal, Royalties, For writing and updating chapters in GU Oncology: Up-To-Date online textbook; Financial Interests, Institutional, Funding, National Chair: BMS, Merck, Exelixis, AstraZeneca, Takeda, Tracon; Financial Interests, Institutional, Local PI, National Chair: Roche; Financial Interests, Institutional, Funding, National co-chair: Pfizer, EMD-Serono; Financial Interests, Institutional, Funding, Chair of trial: Lilly; Financial Interests, Institutional, Local PI: Surface Oncology, GSK; Financial Interests, Institutional, Funding, SC member: Eisai; Financial Interests, Institutional, Funding, National co-chair on 3 ongoing trials: ALLIANCE Cooperative Group; Financial Interests, Institutional, Research Grant, for GU oncology translational research through IION program: BMS; Financial Interests, Institutional, Research Grant, for GU oncology translational research: Exelixis; Financial Interests, Institutional, Research Grant, For Health outcomes research: Roche; Financial Interests, Institutional, Local PI, leads trials as PI: Nikang; Non-Financial Interests, Leadership Role, Co-Chair of the meeting, 2019- current and BOD member (unpaid): Kidney Cancer Research Summit of KidneyCAN; Non-Financial Interests, Principal Investigator, Trial Global and National PI with GU Cancers, mostly Kidney Cancer: Multiple Academic and Industry entities; Non-Financial Interests, Personal, Other, Track Leader/Session chair/Speaker/Discussant: ASCO; Non-Financial Interests, Personal, Other, Speaker/Discussant/Track Leader: ESMO; Non-Financial Interests, Institutional, Other, Access to genomic database: Foundation Med, Guardant, Invitae; Non-Financial Interests, Personal, Other, Grants reviewers: AACR; Non-Financial Interests, Personal, Other, Reviewer of papers: Various journals (e.g. NEJM, Lancet, JCO); Non-Financial Interests, Personal, Other, Medical writing and editorial assistance support (e.g. ClinicalThinking, Envision Pharma Group, Fishawack Group of Companies, Health Interactions, Parexel, Oxford PharmaGenesis, PharmaGenesis, and others). However, first draft frequently initiated by myself when I am 1st author: Medical Communication; Non-Financial Interests, Member: ASCO, AACR; Non-Financial Interests, Other, Political vote usually as “independent”, not a member of any political party. I am an issue voter: General US Politics; Other, Employee at DFCI. Please see https://www.dana-farber.org/ for mission statement (non-profit hospital). I am also the past President of Medical Staff at DFCI 2015-2018: Dana-Farber Cancer Institute (DFCI); Other, Professor at HMS, Please see https://hms.harvard.edu/ for mission statement (non-profit school): Harvard Medical School (HMS); Other, The institution filed patents related to biomarkers of immune checkpoint blockers, and circulating tumor DNA. No money made and some patents were abandoned: Filed patents.