Lucitanib Clinical Development Overview

Lucitanib, is an investigational angiogenesis inhibitor, including vascular endothelial growth factor receptors 1 through 3 (VEGFR 1-3), platelet-derived growth factor receptors alpha and beta (PDGFRα/β) and fibroblast growth factor receptors 1 through 3 (FGFR 1-3). Emerging clinical data support the combination of angiogenesis inhibitors and immunotherapy to increase effectiveness in multiple cancer indications. Angiogenic factors, such as vascular endothelial growth factor (VEGF), are frequently up-regulated in tumors and create an immunosuppressive tumor microenvironment. Use of antiangiogenic drugs may reverse this immunosuppression and augment response to immunotherapy.

Clovis has global rights (excluding China) for lucitanib.

Recent data for a drug that inhibits these same three pathways - when combined with a PD-1 inhibitor - are extremely encouraging and represent a scientific rationale for the development of lucitanib in combination with a PD-1 inhibitor. The LIO-1 study, evaluating lucitanib and nivolumab in combination in advanced solid tumors (Phase 1b) and in gynecologic cancers, including a broad spectrum of ovarian and endometrial subtypes including clear cell disease and patients with cervical cancer (Phase 2) are now underway. An abstract describing the initial Phase 1b clinical experience of lucitanib in combination with nivolumab (LIO-1) has been accepted as an e-poster for the 2020 European Society of Medical Oncology (ESMO) Virtual Congress to be held in September.  In addition, the Phase 2 portion of LIO-1 recently opened for enrollment and treated the first patient in the trial, and a Trials-In-Progress e-poster describing the trial design was also accepted for the 2020 ESMO Virtual Congress.

Based on encouraging data of VEGF and PARP inhibitors in combination, a Phase 1b/2 study of lucitanib in combination with rucaparib in advanced ovarian cancer is also enrolling as an arm of the SEASTAR study. An initial data e-poster was accepted for the 2020 ESMO Virtual Congress.

Lucitanib Scientific Presentations

Initial clinical experience of lucitanib + nivolumab in advanced metastatic solid tumours: data from the phase 1b/2 LIO-1 study (CO-3810-101; NCT04042116)

Poster Presentation 2020 ESMO Virtual Meeting

LIO-1: A Phase 2 study of lucitanib + nivolumab in patients (pts) with gynaecological tumours (CO-3810-101; NCT04042116; ENGOT-GYN3/AGO/LIO)

Poster Presentation 2020 ESMO Virtual Meeting

Application of Machine Learning and Grid Search Approaches to Minimize Lucitanib Pharmacokinetic Variability Following Different Dosing Regimens

Poster Presentation 2020 AACR Virtual Meeting II

The Combination of a Mouse Ortholog of ALKS 4230, a Selective Agonist of the Intermediate-Affinity IL-2 Receptor, and the Angiogenesis Inhibitor Lucitanib Enhances Antitumor Activity

Poster Presentation 2020 AACR Virtual Meeting II

Combination of the Angiogenesis Inhibitor Lucitanib with Immune Checkpoint Blockade Augments Anti-tumor Activity in Syngeneic Models

Presented at 2019 SITC