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Found 1 Presentation For Request "1073TiP"

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1073TiP - A phase I, first-in-human, multicenter, open-label, dose-escalation study of IPH5201 as monotherapy or in combination with durvalumab ± oleclumab in advanced solid tumours

Presentation Number
1073TiP
Speakers
  • John Powderly (Huntersville, United States of America)
Date
17.09.2020

Abstract

Background

CD39, an extracellular enzyme, is overexpressed in the tumor microenvironment, on both tumor infiltrating cells and stromal cells in several cancer types. CD39 promotes immunosuppression by degrading adenosine triphosphate (ATP) into adenosine monophosphate (AMP), that is then further degraded into adenosine by CD73. IPH5201, an anti-CD39 blocking monoclonal antibody, has the potential to promote accumulation of immune-stimulatory ATP and reduce the formation of immunosuppressive adenosine, thereby leading to increased antitumor immunity for multiple tumor types. Preclinical studies demonstrated that IPH5201, in combination with PD-L1 checkpoint inhibitors, increased antitumor efficacy versus a PD-L1 inhibitor alone. This is a phase I, first-in-human, multicenter, open-label, dose-escalation study of IPH5201 as monotherapy or in combination with durvalumab (anti–PD-L1) ± oleclumab (anti-CD73) in patients with advanced solid tumors.

Trial design

Eligible subjects are aged ≥18 years, with advanced solid tumors, and an ECOG PS of ≤1, no conventional or investigational anticancer therapy (eg, anti–CTLA-4, anti–PD-1, anti–PD-L1 antibodies) within 21 days prior to the first dose and no prior agents targeting CD73, CD39, or adenosine receptors. The study will consist of 3 distinct dose-escalation parts given every 3 weeks: IPH5201 monotherapy (part 1), IPH5201 + durvalumab (anti–PD-L1; part 2), and IPH5201 + durvalumab + oleclumab (anti-CD73; part 3). Dose escalation will be based on an m-TPI-2 algorithm of 3 to 12 subjects per cohort. For parts 1 and 2, additional pharmacodynamic cohorts will enroll 6 to 12 subjects at a specific dose with mandatory paired biopsies. The primary endpoint will evaluate safety and tolerability and determine the MTD of IPH5201 in monotherapy and in combination with durvalumab +/- oleclumab. Secondary endpoints will evaluate preliminary antitumor activity and characterize pharmacokinetics and immunogenicity. Up to 204 subjects will be enrolled in the United States, France, Spain, and Switzerland.

Clinical trial identification

NCT04261075.

Editorial acknowledgement

Medical writing support, conducted in accordance with Good Publication Practice (GPP3) and the International Committee of Medical Journal Editors (ICMJE) guidelines, was provided by Eli Berdougo, PhD of Oxford PharmaGenesis, Inc., Newtown, PA, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

J. Powderly: Advisory/Consultancy, Speaker Bureau/Expert testimony, Speakers bureau, consultancy/advisory role: Merck; Research grant/Funding (institution), Clinical Trial Funding: EMD Serono; Research grant/Funding (institution), Clinical Trial Funding: Macrogenics; Research grant/Funding (institution), Clinical Trial Funding: InCyte; Research grant/Funding (institution), Clinical Trial Funding: Arcus; Research grant/Funding (institution), Clinical Trial Funding: RAPT Therapeutics; Research grant/Funding (institution), Clinical Trial Funding: Alkermes; Research grant/Funding (institution), Clinical Trial Funding: Tempest; Advisory/Consultancy, Research grant/Funding (institution), Clinical trial funding, consultancy/advisory role: Curis; Research grant/Funding (institution), Clinical Trial Funding: Corvus; Research grant/Funding (institution), Clinical Trial Funding: AbbVie; Advisory/Consultancy, Consultancy/advisory role: AstraZeneca; Research grant/Funding (institution), Clinical Trial Funding: Top Alliance BioSciences; Research grant/Funding (institution), Clinical Trial Funding - BioSciences: Precision for Medicine; Research grant/Funding (institution), Clinical Trial Funding - BioSpecimens: MT Group; Shareholder/Stockholder/Stock options, Non-remunerated activity/ies, are both developing intellectual property for personalized autologous cell therapies: Carolina BioOncology Institute PLLC and BioCytics Inc.; Leadership role, Shareholder/Stockholder/Stock options, Founder and owns stock in Carolina BioOncology Institute PLLC, BioCytics Inc.: Carolina BioOncology Institute PLLC and BioCytics Inc.; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Clinical trial funding, speakers bureau, consultancy/advisory role: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Clinical trial funding, speakers bureau, consultancy/advisory role: Genentech; Shareholder/Stockholder/Stock options, Owns Stock: Iovance; Shareholder/Stockholder/Stock options, Owns Stock: Juno Therapeutics; Shareholder/Stockholder/Stock options, Owns Stock: BlueBird; Shareholder/Stockholder/Stock options, Owns Stock: Kite Pharma; Shareholder/Stockholder/Stock options, Owns Stock: Ziopharm Oncology; Non-remunerated activity/ies: Multiple collaborations with potential future biopharma and biotech sponsors for the Human Applications Laboratory to develop personalized autologous cell therapies. J.C. Bendell: Advisory/Consultancy, Research grant/Funding (institution), Payment to institution for conduct of clinical trial on which Dr. Bendell served as PI: Arrys Therapeutics; Advisory/Consultancy, Research grant/Funding (institution), Payment to institution for conduct of clinical trial on which Dr. Bendell served as PI: BeiGene; Advisory/Consultancy, Research grant/Funding (institution), Payment to institution for conduct of clinical trial on which Dr. Bendell served as PI: Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution), Payment to institution for conduct of clinical trial on which Dr. Bendell served as PI: Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution), Payment to institution for conduct of clinical trial on which Dr. Bendell served as PI: Celgene; Advisory/Consultancy, Other - Payment to institution for consulting services performed by Dr. Bendell: Cerulean; Advisory/Consultancy, Other - Payment to institution for consulting services performed by Dr. Bendell: Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (institution), Payment to institution for conduct of clinical trial on which Dr. Bendell served as PI: Evelo Biosciences; Advisory/Consultancy, Research grant/Funding (institution), Payment to institution for conduct of clinical trial on which Dr. Bendell served as PI: Five Prime Therapeutics; Advisory/Consultancy, Other - Payment to institution for consulting services performed by Dr. Bendell: FORMA Therapeutics; Advisory/Consultancy, Research grant/Funding (institution), Payment to institution for conduct of clinical trial on which Dr. Bendell served as PI: Genentech; Advisory/Consultancy, Research grant/Funding (institution), Payment to institution for conduct of clinical trial on which Dr. Bendell served as PI: Innate Pharma; Advisory/Consultancy, Other - Payment to institution for consulting services performed by Dr. Bendell: Janssen; Advisory/Consultancy, Research grant/Funding (institution), Payment to institution for conduct of clinical trial on which Dr. Bendell served as PI: Merck; Advisory/Consultancy, Research grant/Funding (institution), Payment to institution for conduct of clinical trial on which Dr. Bendell served as PI: Merrimack Pharmaceuticals; Advisory/Consultancy, Other - Payment to institution for consulting services performed by Dr. Bendell: Moderna Therapeutics; Advisory/Consultancy, Research grant/Funding (institution), Payment to institution for conduct of clinical trial on which Dr. Bendell served as PI: Novartis; Advisory/Consultancy, Research grant/Funding (institution), Payment to institution for conduct of clinical trial on which Dr. Bendell served as PI: Roche; Advisory/Consultancy, Research grant/Funding (institution), Payment to institution for conduct of clinical trial on which Dr. Bendell served as PI: Seattle Genetics; Advisory/Consultancy, Research grant/Funding (institution), Payment to institution for conduct of clinical trial on which Dr. Bendell served as PI: Taiho Oncology; Advisory/Consultancy, Other - Payment to institution for consulting services performed by Dr. Bendell: Tolero Pharmaceuticals; Advisory/Consultancy, Other - Payment to institution for consulting services performed by Dr. Bendell: Translational Drug Development; Research grant/Funding (institution), Payment to institution for conduct of clinical trial on which Dr. Bendell served as PI: Abbvie; Research grant/Funding (institution), Payment to institution for conduct of clinical trial on which Dr. Bendell served as PI: Stemcentrx; Research grant/Funding (institution), Payment to institution for conduct of clinical trial on which Dr. Bendell served as PI: ADC Therapeutics; Research grant/Funding (institution), Payment to institution for conduct of clinical trial on which Dr. Bendell served as PI: Agios; Research grant/Funding (institution), Payment to institution for conduct of clinical trial on which Dr. Bendell served as PI: Arcus Biosciences; Research grant/Funding (institution), Payment to institution for conduct of clinical trial on which Dr. Bendell served as PI: Array BioPharma; Research grant/Funding (institution), Payment to institution for conduct of clinical trial on which Dr. Bendell served as PI: AstraZeneca; Research grant/Funding (institution), Payment to institution for conduct of clinical trial on which Dr. Bendell served as PI: Bayer; Research grant/Funding (institution), Payment to institution for conduct of clinical trial on which Dr. Bendell served as PI: Bellicum Pharmaceuticals; Research grant/Funding (institution), Payment to institution for conduct of clinical trial on which Dr. Bendell served as PI: Bicycle Therapeutics; Research grant/Funding (institution): Blueprint Medicine; Research grant/Funding (institution): Boston Biomedical; Research grant/Funding (institution): Calithera Biosciences; Research grant/Funding (institution): Cyteir Therapeutics; Research grant/Funding (institution): CytomX; Research grant/Funding (institution): eFFECTOR Therapeutics; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): Forty Seven; Research grant/Funding (institution): Gilead Sciences; Research grant/Funding (institution): Gossamer Bio; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Leap Therapeutics; Research grant/Funding (institution): MacroGenics; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): Merus; Research grant/Funding (institution): Millennium Pharmaceuticals; Research grant/Funding (institution): NGM Biopharmaceuticals; Research grant/Funding (institution): Novocure; Research grant/Funding (institution): Oncologie; Research grant/Funding (institution): OnocMed Pharmaceuticals; Research grant/Funding (institution): Pieris Pharmaceuticals; Research grant/Funding (institution): Revolution Medicines; Advisory/Consultancy, Research grant/Funding (institution): Rgenix; Research grant/Funding (institution): SynDevRx; Research grant/Funding (institution): Synthorx; Research grant/Funding (institution): Takeda Pharmaceuticals; Research grant/Funding (institution): Tarveda; Research grant/Funding (institution): Tempest Therapeutics; Research grant/Funding (institution): Tracon Pharmaceuticals; Research grant/Funding (institution): Unum Therapeutics. B.A. Carneiro: Advisory/Consultancy: Foundation Medicine; Advisory/Consultancy: EMD Serono; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Actuate therapeutics; Advisory/Consultancy: Tempus. A. Italiano: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (self), Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: ImmuneDesign; Honoraria (self), Advisory/Consultancy: Epizyme; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bayer; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self): Novartis; Research grant/Funding (institution): AstraZeneca/MedImmune; Research grant/Funding (institution): PharmaMar; Research grant/Funding (institution): MSD Oncology; Research grant/Funding (institution): Merck Serono. T. Macarulla Mercadé: Travel/Accommodation/Expenses, Personal fees: Baxalta; Research grant/Funding (institution), Travel/Accommodation/Expenses, I have received support for travel or accommodation: Bayer; Research grant/Funding (institution), Travel/Accommodation/Expenses, Personal fees: Celgene; Travel/Accommodation/Expenses, Personal fees: Genzyme; Travel/Accommodation/Expenses, I have received support for travel or accommodation: H3B; Travel/Accommodation/Expenses, Personal fees: QED; Travel/Accommodation/Expenses, I have received support for travel or accommodation: Merck; Travel/Accommodation/Expenses, Personal fees: Roche; Travel/Accommodation/Expenses, I have received support for travel or accommodation: Sanofi; Travel/Accommodation/Expenses, Personal fees: Shire; Research grant/Funding (institution): Agios; Research grant/Funding (institution): Aslan; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Hallozyme; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Merimarack; Research grant/Funding (institution): Millennium; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Novocure; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Pharmacyclics; Research grant/Funding (institution): Roche. M. Imbimbo: Travel/Accommodation/Expenses, Personal fees: BMS. C. Massard: Advisory/Consultancy: Amgen; Advisory/Consultancy: Astellas; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bayer; Advisory/Consultancy: BeiGene; Advisory/Consultancy: BMS; Advisory/Consultancy: Celgene; Advisory/Consultancy: Debiopharm; Advisory/Consultancy: Genentech; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Janssen; Advisory/Consultancy: Lilly; Advisory/Consultancy: MedImmune; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Orion. All other authors have declared no conflicts of interest.

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