Abstract 556P
Background
Proangiogenic factors contribute to immunosuppression in the tumour microenvironment. Inhibiting angiogenesis with a tyrosine kinase inhibitor (TKI) may attenuate these signals and improve immunotherapy efficacy. This study is investigating the safety and efficacy of the angiogenesis inhibitor lucitanib + nivolumab.
Methods
The phase Ib dose-escalation part of LIO-1 will determine the recommended phase II dose of lucitanib in combination with nivolumab (fixed dose, 480 mg IV once every 4 weeks) in patients (pts) with an advanced refractory or progressive solid tumour and no satisfactory treatment options. The lucitanib dose has been evaluated at a once-daily dose of 6, 8 and 10 mg. Dose-limiting toxicities (DLTs) were assessed during the first 28 days of treatment. Tumour response was assessed by investigators per RECIST v1.1. Steady-state pharmacokinetic (PK) evaluation was performed for lucitanib. Fresh tumour biopsies were collected prior to study entry for translational analysis of biomarkers such as tumour mutation burden, microsatellite instability and PD-L1 expression.
Results
As of 14 May 2020, 15 pts have been treated with 6 mg (n=7), 8 mg (n=5) or 10 mg (n=3) lucitanib in combination with nivolumab. In the first cohort of 4 pts evaluating 6 mg, 1 DLT (Grade [G]3 proteinuria) was observed, leading to discontinuation. This pt also experienced G3 hypertension (HTN), G2 fatigue and G1 oedema. A further 3 pts were enrolled at 6 mg; no further DLTs were reported. No DLTs were reported at 8 or 10 mg. Across all doses, G3 treatment-related AEs included HTN (3 pts) and diarrhoea (1 pt). Treatment-emergent HTN was otherwise G1/2, and readily managed with close monitoring and early antihypertensive therapy. To date, there have been 2 confirmed PRs (cervical and anal cancer), 5 SD and 2 PD. Of the remaining pts, 4 are too early to assess and 2 were non-evaluable due to early discontinuation (clinical progression [n=1] or non-compliance [n=1]). Initial PK data indicate high interpatient variability and dose-proportional exposure.
Conclusions
Initial data suggest that lucitanib + nivolumab can be combined, with promising signs of antitumour activity.
Clinical trial identification
NCT04042116.
Editorial acknowledgement
Medical writing support was provided by Andrew Croskery, MPharm (Clovis Oncology, Ltd., London, UK); editorial support funded by Clovis Oncology was provided by Frederique H. Evans of Ashfield Healthcare Communications.
Legal entity responsible for the study
Clovis Oncology, Inc.
Funding
Clovis Oncology, Inc.
Disclosure
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): Hutchison 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; 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. 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: Shareholder/Stockholder/Stock options, Full/Part-time employment: Clovis Oncology . D. Lepley: Shareholder/Stockholder/Stock options, Full/Part-time employment: Clovis Oncology. R. Dusek: Shareholder/Stockholder/Stock options, Full/Part-time employment: Clovis Oncology. M. Liao: Shareholder/Stockholder/Stock options, Full/Part-time employment: Clovis Oncology. T. Cameron: Research grant/Funding (institution), Full/Part-time employment: Clovis Oncology. All other authors have declared no conflicts of interest.