Abstract 885TiP
Background
Pro-angiogenic growth factors secreted by tumours promote the generation of new blood vessels and mediate immunosuppression, which may dampen the effect of immune checkpoint inhibitors. Inhibiting angiogenesis with a tyrosine kinase inhibitor (TKI) may therefore relieve immunosuppression. Lucitanib is a potent TKI that selectively inhibits VEGFR1–3, PDGFRα/β and FGFR1–3 and may improve the efficacy of the anti-PD-1 antibody nivolumab when the two are given in combination. LIO-1 is a phase Ib/II study evaluating the safety and efficacy of lucitanib + nivolumab. The recommended phase II dose (RP2D) of lucitanib will be determined in the phase Ib part of LIO-1.
Trial design
This phase II dose-expansion will evaluate the safety and efficacy of lucitanib + nivolumab in 4 gynaecological tumour cohorts (endometrial, ovarian, cervical, and endometrial/ovarian clear-cell cancers) in a Simon 2-stage study design. Pts will initially receive oral lucitanib once daily at the RP2D + nivolumab (480 mg intravenous dose once every 4-week cycle). As lucitanib has high pharmacokinetic (PK) variability and an adverse event profile typical of drugs in this class, an individual safety-based dose-titration approach will be employed. Lucitanib dose will be escalated after cycle 1 and again after cycle 2 if dose-escalation criteria are met. Doses may be interrupted or reduced for tolerability. This approach will allow individual optimisation of lucitanib exposure to maintain dose intensity and anticipated efficacy benefits while accounting for tolerability. The primary endpoint will be investigator-assessed confirmed best overall response per RECIST v1.1. Secondary endpoints include safety and tolerability, duration of response, disease control rate, progression-free survival, overall survival, and characterisation of the PK profile of lucitanib. Recent tumour samples will be analysed for biomarkers (ie, tumour mutation burden, microsatellite instability, and PD-L1 expression), which may be associated with response to treatment. Approximately 28 sites in Europe and the United States will be open for enrolment. This phase II study will be performed according to the ENGOT Model D.
Clinical trial identification
NCT04042116.
Editorial acknowledgement
Medical writing support funded by Clovis Oncology was provided by Stephen Mason, PhD, of Ashfield Healthcare Communications.
Legal entity responsible for the study
Clovis Oncology, Inc.
Funding
Clovis Oncology, Inc.
Disclosure
N. Concin: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Mersana; Advisory/Consultancy: Seattle Genetics; Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: Genmab; Travel/Accommodation/Expenses: Roche; Honoraria (self), Travel/Accommodation/Expenses: Medscape. A. González Martín: Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Amgen; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Genmab; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: GSK/Tesaro; Advisory/Consultancy: Immunogen; Advisory/Consultancy: MSD; Advisory/Consultancy: Oncoinvent; Advisory/Consultancy: Pfizer/Merck; Advisory/Consultancy, Travel/Accommodation/Expenses: Pharmamar; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Roche. I.B. Vergote: Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Carrick Therapeutics; Advisory/Consultancy: Debiopharm; Advisory/Consultancy: Deciphera Pharmaceuticals; Advisory/Consultancy: F. Hoffmann-La Roche; Advisory/Consultancy, Research grant/Funding (self): Genmab; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Immunogen; Advisory/Consultancy: Millennium Pharmaceuticals; Advisory/Consultancy: MSD; Advisory/Consultancy: Octimet Oncology; Advisory/Consultancy, Research grant/Funding (self): Oncoinvent AS; Advisory/Consultancy: PharmaMar; Advisory/Consultancy: Sotio; Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy: Verastem Oncology; Travel/Accommodation/Expenses: MSD/Merck; Research grant/Funding (self), Travel/Accommodation/Expenses: Roche. S. Pignata: Honoraria (self): Clovis Oncology; Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self): Incyte Pfizer; Honoraria (self), Research grant/Funding (self): MSD; Honoraria (self), Research grant/Funding (self): Pfizer; Honoraria (self): PharmaMar; Honoraria (self), Research grant/Funding (self): Roche; Honoraria (self): Tesaro/GSK. P. Harter: Honoraria (self): ASCO; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self): MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (self): Sotio; Honoraria (self): Stryker; Honoraria (self): Tesaro; Honoraria (self): Zai Lab; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: GSK; Advisory/Consultancy: Immunogen; Advisory/Consultancy: Lilly; Advisory/Consultancy: MSD/Merck; Advisory/Consultancy, Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): DFG; Research grant/Funding (institution): DKH; Research grant/Funding (institution): European Union; Research grant/Funding (institution): Genmab. C.C. Gunderson: Advisory/Consultancy, Research grant/Funding (self): Clovis Oncology; Advisory/Consultancy: Agenus; Advisory/Consultancy: Cordgenics; Advisory/Consultancy: GSK/Tesaro; Advisory/Consultancy: Leap Therapeutics; Research grant/Funding (self): Genentech. K. Wride, D. Lepley, R. Dusek, J. Go, S. Hurley, T. Cameron: Shareholder/Stockholder/Stock options, Full/Part-time employment: Clovis Oncology. E. P. Hamilton: Honoraria (institution), Research grant/Funding (institution): AstraZeneca; Honoraria (institution), Research grant/Funding (institution): Black Diamond; Honoraria (institution), Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (institution), Research grant/Funding (institution): Daiichi Sankyo; Honoraria (institution), Research grant/Funding (institution): Genentech/Roche; Honoraria (institution), Research grant/Funding (institution): Lilly; Honoraria (institution), Research grant/Funding (institution): Mersana Therapeutics; Honoraria (institution): NanoString; Honoraria (institution), Research grant/Funding (institution): Novartis; Honoraria (institution), Research grant/Funding (institution): Pfizer; Honoraria (institution), Research grant/Funding (institution): Puma Biotechnology; Honoraria (institution), Research grant/Funding (institution): Silverback Therapeutics; Research grant/Funding (institution): Clovis Oncology; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Acerta; Research grant/Funding (institution): Aravive; Research grant/Funding (institution): ArQule; Research grant/Funding (institution): Arvinas; Research grant/Funding (institution): BerGenBio; Research grant/Funding (institution): Compugen; Research grant/Funding (institution): Curis; Research grant/Funding (institution): Cytomx; Research grant/Funding (institution): Deciphera; Research grant/Funding (institution): Effector; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): Fochon; Research grant/Funding (institution): FujiFilm; Research grant/Funding (institution): G1Therapeutics; Research grant/Funding (institution): H3 Biomedicine Research grant/Funding (institution): Harpoon; Research grant/Funding (institution): Hutchinson MediPharma; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): InventisBio; Research grant/Funding (institution): Karyopharm Therapeutics; Research grant/Funding (institution): Leap Therapeutics;; Research grant/Funding (institution): Lycera; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): Medivation;; Research grant/Funding (institution): Merus; Research grant/Funding (institution): Millenium; Research grant/Funding (institution): Molecular Templates; Research grant/Funding (institution): Nucana; Research grant/Funding (institution): OncoMed; Research grant/Funding (institution): Orinove; Research grant/Funding (institution): Radius Health; Research grant/Funding (institution): Regeneron; Research grant/Funding (institution): Rgenix; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Sermonix Pharmaceuticals; Research grant/Funding (institution): StemCentrx; Research grant/Funding (institution): Sutro; Research grant/Funding (institution): Syndax; Research grant/Funding (institution): Syros; Research grant/Funding (institution): Taiho Pharmaceutical; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): TapImmune; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): Torque Therapeutics; Research grant/Funding (institution): Unum Therapeutics; Research grant/Funding (institution): Verastem; Research grant/Funding (institution): Zenith Epigenetics; Research grant/Funding (institution): Zymeworks. All other authors have declared no conflicts of interest.