On July 17, 2020 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that four abstracts showcasing non-clinical data from rucaparib and lucitanib development programs have been accepted for on-demand viewing and publication at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II, June 22 – 24, 2020 (Press release, Clovis Oncology, JUN 17, 2020, View Source [SID1234561173]).
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The accepted abstracts summarize findings from pre-clinical studies evaluating the PK, PD and anti-tumor activity of rucaparib,an oral, small molecule PARP inhibitor in orthotopic and intracranial mouse models, and its synergy with CHK1 inhibition in tumor cell lines. Additional abstracts include findings from a study of the pharmacokinetics of lucitanib, an oral, potent inhibitor of tyrosine kinase activity, in a simulated patient population to inform dosing-regimen selection, and from a pre-clinical study evaluating the anti-tumor efficacy and mechanism of action of lucitanib in combination with a mouse ortholog of ALKS 4230, a selective agonist of the intermediate affinity IL-2 receptor, in a mouse colon cancer model. Lucitanib and ALKS 4230 are both development-stage compounds.
"Data from our ongoing non-clinical studies underscore our commitment to pursuing innovative research that advances novel therapies for cancer patients," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "In particular, we are pleased to present new, non-clinical data exploring the PK/PD of our PARP inhibitor Rubraca, evaluating the synergies of PARP and CHK1 inhibition in combination, as well as important data for lucitanib to understand optimal dosing and use in combination with other anticancer agents to treat solid tumors."
The following Clovis-sponsored, collaborator-sponsored and investigator-sponsored abstracts will be available as AACR (Free AACR Whitepaper) 2020 Virtual Poster Session presentations. E-posters, and when available, accompanying audio descriptions, will be available for on-demand viewing beginning 9:00 a.m. EDT Monday, June 22, and will remain available for viewing by registered attendees for at least three months after the virtual meeting.
Abstract Number: 3026 / 14 – Evaluation of brain pharmacokinetics (PK) and tumor growth inhibition of PARP inhibitors in mouse xenograft models using semi-mechanistic PK/pharmacodynamic (PD) modeling
Presenting Author: Michelle Liao
Session: Pharmacokinetics / Pharmacodynamics
Abstract Number: 3027 / 15 – Application of machine learning and grid search approaches to minimize lucitanib pharmacokinetic variability following different dosing regimens
Presenting Author: Michelle Liao
Session: Pharmacokinetics / Pharmacodynamics
Abstract Number: 2202 / 7 – 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
Presenting Author: Jared E. Lopes
Session: Combination Immunotherapies 2
In addition, the three previous posters will be available on the Clovis Oncology website once they become available on the AACR (Free AACR Whitepaper) virtual meeting website.
Abstract Number: 1375 / 11 – Investigating synergy between CHK1 and PARP inhibitors in BRCA2 mutant and restored cells
Presenting Author: Hannah L. Smith
Session: Mechanisms of DNA Damaging Therapeutics
About Rubraca (rucaparib)
Rubraca is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in multiple tumor types, including ovarian and metastatic castration-resistant prostate cancers, as monotherapy, and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway. Clovis holds worldwide rights for Rubraca.
In the United States, Rubraca is approved for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. Rubraca is also approved in the United States for the treatment of adult patients with deleterious BRCA mutation (germline and/or somatic) associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more chemotherapies and selected for therapy based on an FDA-approved companion diagnostic for Rubraca. Additionally, Rubraca is indicated for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy. This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
In Europe, Rubraca is approved for the maintenance treatment of adults with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy. Rubraca is also approved in Europe for the treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with two or more prior lines of platinum-based chemotherapy, and who are unable to tolerate further platinum-based chemotherapy. Rubraca is indicated for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy.
Rubraca is an unlicensed medical product outside of the U.S. and Europe.
About Lucitanib
Lucitanib is an oral, potent inhibitor of the tyrosine kinase activity of vascular endothelial growth factor receptors 1 through 3 (VEGFR1-3), platelet-derived growth factor receptors alpha and beta (PDGFRα/β) and fibroblast growth factor receptors 1 through 3 (FGFR1-3). 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 reverses this immunosuppression and can augment response to immunotherapy.
Lucitanib is an unlicensed medical product.