Hugh Giovinazzo

Pharmaceutical Industry Perspectives on Exposure‐Response Confounding in Large Molecule Therapeutics: Results From an IQ Consortium Survey

Engie Salama, Manisha Lamba, Sihem Ait‐Oudhia, Ellen Wang et autres

Exposure-response (ER) analyses assessing the efficacy of large molecule therapeutics are often susceptible to confounding, where associations between drug exposure and patient disease severity can obscure true ER signals and complicate dose selection. To better understand the pharmaceutical industry perspectives on this …

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Triptolide sensitizes cancer cells to nucleoside DNA methyltransferase inhibitors through inhibition of DCTPP1-mediated cell-intrinsic resistance

Jianyong Liu, Qingli He, Jianya Zhou, Ajay Vaghasia et autres

Abnormal DNA hypermethylation mediated by DNA methyltransferases (DNMT) is a nearly universal hallmark of human cancers. However, while DNA methyltransferase inhibitors (DNMTi) such as decitabine and azacitidine are effective in treating myelodysplatic syndrome/leukemia, they have had limited utility for the majority of …

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Consideration of adjusted ideal body weight dosing in BG-C9074 (B7-H4–targeting ADC) from pharmacokinetics, efficacy, and safety perspectives.

Hugh Giovinazzo, Ramil Abdrashitov, Yaogeng Wang, Garret Winkler et autres

3029 Background: B7-H4 is a transmembrane glycoprotein that is upregulated in a variety of solid tumors. BG-C9074 is an investigational topoisomerase I inhibitor antibody-drug conjugate (ADC) that targets B7-H4. We present results of the pharmacokinetic (PK) and exposure-response (ER) analyses supporting the …

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A phase 1 study of BGB-B2033 (GPC3 x 4-1BB bispecific antibody) monotherapy in patients with selected advanced or metastatic solid tumors: First disclosure of clinical data.

Hong Jae Chon, J Hong, Xueli Bai, Tao Zhang et autres

3016 Background: GPC3 is a tumor-specific antigen that is highly expressed in hepatocellular carcinoma (HCC) and squamous non-small cell lung cancer. 4-1BB is a co-stimulatory receptor on activated T cells that promotes proliferation, survival and cytolysis of T cells. BGB-B2033, a novel, …

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First-in-human study of BG-C9074 (B7-H4–targeting ADC) in advanced solid tumors: Dose escalation and safety expansion.

Binghe Xu, Linda R. Mileshkin, Andrew Parsonson, Qi Gao et autres

3013 Background: B7-H4, a transmembrane glycoprotein, has limited expression in normal tissue, but is upregulated in a variety of solid tumors. BG-C9074 is an investigational topoisomerase I inhibitor antibody-drug conjugate (ADC) that targets B7-H4. We present results of monotherapy dose escalation and …

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A phase I study of the OX40 agonist BGB-A445 with or without tislelizumab, an anti–PD-1 monoclonal antibody, in patients with advanced solid tumors: dose-escalation results

Jayesh Desai, Sanjeev Deva, Bo Gao, Kunyu Yang et autres

PURPOSE: OX40 may stimulate T-cell activation, potentially enhanced with checkpointinhibition. Results are from the dose-escalation part of an ongoing, multicenter, open-label study (NCT04215978, registered 30 December 2019) investigating OX40 agonist BGB-A445 alone or with anti-PD-1 antibody tislelizumab in patients with advanced solid …

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A phase 1 study of the OX40 agonist BGB-A445, with or without tislelizumab, an anti-PD-1 monoclonal antibody, in patients with advanced NSCLC, HNSCC, or NPC.

Min Hee Hong, Byoung Chul Cho, Sanjeev Deva, Fang Ma et autres

2525 Background: BGB-A445 is a monoclonal antibody OX40 agonist that does not compete with the natural OX40 ligand, reducing the likelihood of a hook effect and distinguishing it from other OX40-targeting therapies. Here, we present results from the dose expansion portion of …

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A phase 2 study of the OX40 agonist BGB-A445, in combination with docetaxel or BGB-15025, an HPK1 inhibitor, in patients with NSCLC pretreated by anti-PD-(L)1 antibodies.

Tae Min Kim, Hai‐Yan Liu, Byoung Chul Cho, Young Ju Lee et autres

e14513 Background: OX40, an immune costimulatory receptor mainly expressed on activated T cells, plays a role in T cell survival, proliferation, and proinflammatory cytokine expression. BGB-A445 is a novel mAb agonist against OX40 with high specificity and affinity that showed preclinical antitumor …

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First-in-human study of BG-C9074, a B7-H4-targeting ADC in patients with advanced solid tumors: Preliminary results of the dose-escalation phase.

Cesar A. Perez, Linda Mileshkin, Garret Albert Winkler, Shuai Yuan et autres

3033 Background: B7-H4 is a transmembrane glycoprotein in the B7 superfamily with limited expression in normal tissue but is upregulated in solid tumors including cholangiocarcinoma, breast, ovarian, and endometrial cancers. BG-C9074 is an investigational topoisomerase I inhibitor antibody-drug conjugate. This abstract presents …

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Alternative Dosing Regimens of Tislelizumab Using a Pharmacometrics Model‐Based Approach

Ahsan Rizwan, Hugh Giovinazzo, Yu Tian, Yuying Gao et autres

ABSTRACT Tislelizumab 200 mg once every 3 weeks (Q3W) is approved for the treatment of multiple cancers. We used a model‐based approach to propose three alternative dosing regimens, 150 mg Q2W, 300 mg Q4W, and 400 mg Q6W, with the aims of …

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Hepatic Dysfunction Quantified by HepQuant DuO Outperforms Child‐Pugh Classification in Predicting the Pharmacokinetics of Ampreloxetine

Jitendra Kanodia, Hugh Giovinazzo, Wayne Yates, David L. Bourdet et autres

HepQuant tests quantify liver function from clearance of deuterium‐ and 13C‐labeled cholates administered either intravenously and orally (SHUNT) or orally (DuO). Hepatic impairment studies have relied on clinical or laboratory criteria like Child‐Pugh classification to categorize the degree of hepatic dysfunction. We …

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Mononuclear phagocyte system function and nanoparticle pharmacology in obese and normal weight ovarian and endometrial cancer patients

David A. Barrow, Hugh Giovinazzo, Brittney Starling, G. Song et autres

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