A5083922534- PARP inhibition in cancer therapy
- Cancer therapeutics and mechanisms
- Lung Cancer Research Studies
- Neutropenia and Cancer Infections
- DNA Repair Mechanisms
- Chronic Myeloid Leukemia Treatments
- Cancer, Hypoxia, and Metabolism
- Ovarian cancer diagnosis and treatment
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Glioma Diagnosis and Treatment
- Advanced Breast Cancer Therapies
- Chronic Lymphocytic Leukemia Research
- Cell death mechanisms and regulation
- Peptidase Inhibition and Analysis
- Acute Myeloid Leukemia Research
- Cancer Immunotherapy and Biomarkers
- Phagocytosis and Immune Regulation
- Toxin Mechanisms and Immunotoxins
- Biosimilars and Bioanalytical Methods
- Cancer Treatment and Pharmacology
- Calcium signaling and nucleotide metabolism
- Angiogenesis and VEGF in Cancer
- Advanced Causal Inference Techniques
- Insect Resistance and Genetics
- Growth Hormone and Insulin-like Growth Factors
CSL (Switzerland)
2024
AbbVie (United States)
2016-2024
University of Florida
2016
Columbus Oncology and Hematology Associates
2016
Reckitt Benckiser (United States)
2016
Temple University
2011-2012
Targeting the BCL-X
Venetoclax is a selective, first-in-class, B-cell lymphoma-2 inhibitor that has demonstrated clinical efficacy in several hematological malignancies. Two studies evaluated the relative bioavailability of venetoclax healthy subjects: (1) bioequivalence study to compare film-coated tablet with an earlier uncoated and (2) food effect evaluate on pharmacokinetics. Both were open-label, single-dose, crossover studies. In study, 15 subjects received single dose 50 mg under nonfasting conditions,...
This study examined safety, pharmacokinetics, and efficacy of veliparib, a PARP inhibitor, combined with carboplatin etoposide in patients extensive-stage (ED) small cell lung cancer (SCLC) other solid tumors.The 3 + design was used for dose escalation oral veliparib combination (AUC 5 on day 1) (100 mg/m2 days 1-3) 21-day cycles. Veliparib explored from 80 to 240 mg b.i.d. 7-day, 14-day, or continuous schedules. Patients without disease progression continued maintenance monotherapy...
Abstract Eftozanermin alfa (eftoza), a second-generation tumor necrosis factor-related apoptosis-inducing ligand receptor (TRAIL-R) agonist, induces apoptosis in cells by activation of death receptors 4/5. This phase 1 dose-escalation/dose-optimization study evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary activity eftoza patients with advanced solid tumors. Patients received 2.5–15 mg/kg intravenously on day or 1/day 8 every 21 days dose-escalation phase, 1.25–7.5...
Metronomic dosed (MD) chemotherapy as opposed to conventional (CD) is considered an alternate strategy target angiogenesis and limit host toxicity. Although this approach promising, there has not been any attempt define optimal metronomic dosing regimens by integrating pharmacokinetic (PK) with pharmacodynamic (PD) measurements. The aim of study was compare the pharmacokinetics pharmacodynamics temozolomide [TMZ, 8-carbamoyl-3-methylidazo(5,1-<i>d</i>)-1,2,3,5-terrazin-4(3<i>H</i>)-one]...
Both combinations of the PARP inhibitor veliparib plus platinum doublet chemotherapy (CT), and programmed death receptor-1 (PD-1) nivolumab CT have demonstrated encouraging efficacy for treatment non-small cell lung cancer (NSCLC). This phase 1 dose-escalation study (NCT02944396) evaluated quadruple combination with in patients unresectable advanced/metastatic NSCLC.Patients were enrolled into five dosing cohorts: received 120 mg twice daily (BID) combined 360 mg, carboplatin AUC 6...
Veliparib (ABT-888) is a potent, orally bioavailable poly(ADP-ribose) polymerase-1 and -2 inhibitor. This phase 1 study evaluated the tolerability, pharmacokinetic profile, safety, preliminary antitumor activity of single-agent veliparib in Japanese patients with advanced solid tumors. Eligible were assigned to treatment at 200 or 400 mg dose; was self-administered twice daily on days 1-28 28-day cycles. Dose escalation, following 3 + design, defined dose-limiting toxicities, maximum...
This phase 1, open‐label, dose‐escalation study was conducted to determine the safety, tolerability, pharmacokinetics and preliminary efficacy of veliparib with carboplatin weekly paclitaxel in Japanese women newly diagnosed, advanced ovarian cancer. Patients received at 100 or 150 mg b.i.d. on days 1–21 (area under concentration–time curve 6 mg/mL•min) day 1 80 mg/m 2 8 15 every 3 weeks for up 21‐day cycles. Dose escalation followed a + design dose‐limiting toxicities, maximum tolerated...
Veliparib is a potent poly(ADP)-ribose polymerase (PARP) 1 and 2 inhibitor that impedes repair of DNA damage induced by cytotoxic radiation therapies. This phase study evaluated veliparib in combination with chemoradiotherapy patients unresectable stage III non-small cell lung cancer (NSCLC).Patients received orally twice daily (BID) escalating doses (60-240 mg, Day -3 to day after last dose radiation) combined weekly carboplatin (area under the curve [AUC] mg/mL/min), paclitaxel (45 mg/m2),...
Veliparib (ABT-888) is an orally bioavailable potent inhibitor of poly(ADP-ribose) polymerase (PARP)-1 and PARP-2. This phase 1 study evaluated the effect veliparib on corrected QT interval using Fridericia's formula (QTcF). Eligible patients with advanced solid tumors received single-dose oral (200 mg or 400 mg) placebo in a 6-sequence, 3-period crossover design. The primary endpoint was difference mean baseline-adjusted QTcF between (∆∆QTcF) at six post-dose time points. Absence clinically...
8510 Background: CRT is standard treatment (Tx) for pts with unresectable stage III NSCLC. Vel, a potent oral PARP1/2 inhibitor, interferes repair of chemotherapy- or radiation-induced DNA damage. In phase 2 study, Vel showed favorable efficacy vs placebo when added to C/P in IV The reported 1 trial assessed the safety and + C/P-based Tx NSCLC (NCT02412371). Methods: Eligible (≥18 yr, NSCLC, no prior therapy) received weekly C area under curve (AUC) P 45 mg/m 60 Gy (2 Gy/day) RT over 6–9...
BRCA-Mutated Advanced Breast Cancer (BROCADE3) is a phase 3 study, evaluating veliparib in combination with carboplatin/paclitaxel continuation as monotherapy if discontinued patients germline BRCA1/2 mutation-associated, advanced human epidermal growth factor receptor 2-negative breast cancer. The objective of the current analysis was to characterize exposure-response relationships for efficacy (progression-free survival [PFS]) and safety this study. Exposure-efficacy analyses PFS were...
8530 Background: The majority of SCLC cases are diagnosed as ED, for which there is a poor prognosis and no curative treatment (Tx). V, potent PARP inhibitor, has been shown in preclinical studies to enhance the antitumor activity platinum-based agents E against SCLC. presented phase 1 dose-escalation (NCT02289690) evaluated V combined with Cb/E. Methods: Pts (≥18 years) ED or other advanced/metastatic solid tumors ≤1 line prior cytotoxic therapy ECOG performance score 0/1 were included....
To assess the impact of coronavirus disease 2019 (COVID-19) pandemic on clinical trials design and conduct, a Working Group was formed by Clinical Pharmacology Leadership within International Consortium for Innovation Quality in Pharmaceutical Development. The collected summarized data IQ member companies' experience conduct trials, extent missed doses missing pharmacokinetic/pharmacodynamic data, implementation mitigation strategies. As August 30, 2023, there have been over 770 million...