Djuro Karanovic

Rilvegostomig for Metastatic Non–Small Cell Lung Cancer: A First-In-Human Phase I/II Clinical Study

Kristoffer Staal Rohrberg, Mariana Brandão, Eduardo Castañón Álvarez, Enriqueta Felip et autres

PURPOSE: Rilvegostomig, an anti-PD-1/TIGIT bispecific antibody, was evaluated in this first-in-human, multicenter, phase I/II, open-label study (NCT04995523) in checkpoint inhibitor (CPI)-experienced patients with programmed death ligand-1 (PD-L1)-positive advanced or metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: In Part A, patients (n …

dk, be, es, ps, nl, jp, kr, au, br, gb, sg (code pays fourni par la source)

CTIM-16. SAFETY AND PRELIMINARY EFFICACY OF AZD1390 + RADIATION THERAPY FOR GLIOBLASTOMA

Patrick Yung Wen, Jonathan T. Yang, Brandon S. Imber, J. Drappatz et autres

Abstract BACKGROUND Glioblastoma is an aggressive cancer; intensity-modulated radiation therapy (IMRT) with concomitant and adjuvant temozolomide is the first-line standard of care. AZD1390, an ataxia telangiectasia mutated kinase inhibitor, aims to augment the efficacy of IMRT without exacerbating neurotoxicity. AZD1390 is optimized …

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OA11.03 Efficacy and Safety of Rilvegostomig, an Anti-PD-1/TIGIT Bispecific, for CPI-naïve Metastatic NSCLC with PD-L1 1-49% or ≥50%

T.J.N. Hiltermann, Hiroki Izumi, B.C. Cho, Sara Bernardes da Cunha et autres

nl, jp, kr, pe, th, es, my, us, cn, be, tw, gb (code pays fourni par la source)

Safety and Preliminary Efficacy of AZD1390 + Radiation Therapy for Glioblastoma

J.T. Yang, Ping Wen, B.S. Imber, Jan Drappatz et autres

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Abstract CT017: Pan-mutant and isoform selective PI3Kα inhibitor, RLY-2608, demonstrates selective targeting in a first-in-human study of PIK3CA-mutant solid tumor patients, ReDiscover trial

Andreas S. Varkaris, Komal L. Jhaveri, Cesar A. Perez, Janice S. Kim et autres

Abstract BACKGROUND: Oncogenic activation of PI3Kα via mutation of PIK3CA is the most common kinase driver event across solid tumors, particularly breast cancer (BC). Alpelisib, an orthosteric inhibitor, validated mutant-PI3Kα as a therapeutic target; however, toxicity from non-selective inhibition of WT PI3Kα …

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Abstract 2795: A food effect and esomeprazole drug-drug interaction study of RLY-4008, a highly selective FGFR2 inhibitor, in healthy subjects

Jinshan Shen, Rick E. Blakesley, Kai Yu Jen, Fabien Ricard et autres

Abstract Background/Introduction: Effective therapies for FGFR2-driven cholangiocarcinoma (CCA) and other advanced solid tumors remain unmet medical needs. RLY-4008 is a potent, highly selective and irreversible FGFR2 inhibitor designed to target both primary FGFR2 oncogenic alterations and clinically relevant resistance mutations. RLY-4008 is …

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Abstract OT3-22-01: First-in-human global multi-center study of RLY-2608, a pan mutant and isoform selective PI3Kα inhibitor, as a single agent in advanced solid tumor patients and in combination with fulvestrant in patients with advanced breast cancer

Andreas S. Varkaris, Erika Paige Hamilton, Jason Timothy Henry, Alexander I. Spira et autres

Abstract Background: Targeting constitutively active mutant kinases with selective small molecule inhibitors is a key therapeutic pillar of precision oncology. Phosphatidylinositol-4,5bisphosphate-3 kinase, catalytic subunit alpha (PIK3CA) mutations leading to oncogenic activation of PI3Kα represent the largest opportunity for this approach in solid …

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First-in-human global multi-center study of RLY-2608, a pan-mutant and isoform-selective PI3Kα inhibitor, as a single agent in patients with advanced solid tumors and in combination with fulvestrant in patients with advanced breast cancer.

Cesar A. Perez, Jason Timothy Henry, Andreas S. Varkaris, Vivek Subbiah et autres

TPS1124 Background: Targeting constitutively active mutant kinases with selective small molecule inhibitors is a key therapeutic pillar of precision oncology. Phosphatidylinositol-4,5bisphosphate-3 kinase, catalytic subunit alpha ( PIK3CA) mutations leading to oncogenic activation of PI3Kα represent the largest opportunity for this approach in …

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Abstract CT244: A phase 1 study of IV MEDI5395, an oncolytic virus, in combination with durvalumab in patients with advanced solid tumors

Grace Kho Dy, Diwakar Davar, Evanthia Galanis, Danielle Townsley et autres

Abstract Background: Oncolytic viruses selectively infect tumors and activate antitumor immune responses via innate and adaptive pathways, which may potentiate the efficacy of immune checkpoint inhibitors. MEDI5395 is a recombinant Newcastle disease virus incorporating a granulocyte macrophage colony-stimulating factor (GM-CSF) transgene that …

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Disseminated and Congenital Toxoplasmosis in a Mother and Child With Activated PI3-Kinase δ Syndrome Type 2 (APDS2): Case Report and a Literature Review of Toxoplasma Infections in Primary Immunodeficiencies

Djuro Karanovic, Ian C. Michelow, Anthony R Hayward, Suk See De Ravin et autres

Phosphoinositide 3-kinase (PI3K) plays an integral role in lymphocyte function. Mutations in PIK3CD and PIK3R1, encoding the PI3K p110 and p85 subunits, respectively, cause increased PI3K activity and result in immunodeficiency with immune dysregulation. We describe here the first cases of disseminated …

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Management of Cytopenias in CTLA4 Haploinsufficiency Using Abatacept and Sirolimus

Gülbû Uzel, Djuro Karanovic, Hua Su, Amy Rump et autres

Abstract Background: CTLA4 is a homodimeric cell surface inhibitory receptor that plays a critical role in maintaining immune system homeostasis by suppressing T-lymphocyte activation and proliferation. Heterozygous germline, loss-of-function mutations in CTLA4, present with a diverse clinical phenotype of recurrent infections, lymphoproliferation, …

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Generalized Pruritus without Fixed Skin Lesions: A Rare Presentation of Adult Mastocytosis

Djuro Karanovic

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