A5040293397- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Peptidase Inhibition and Analysis
- Acute Myeloid Leukemia Research
- Lung Cancer Treatments and Mutations
- Breast Cancer Treatment Studies
- Acute Lymphoblastic Leukemia research
- Chronic Myeloid Leukemia Treatments
- Nanoparticle-Based Drug Delivery
- Brain Metastases and Treatment
- Radiopharmaceutical Chemistry and Applications
- Lung Cancer Research Studies
- Graphene and Nanomaterials Applications
- Protein purification and stability
- Histone Deacetylase Inhibitors Research
- Pancreatic and Hepatic Oncology Research
- Chronic Lymphocytic Leukemia Research
- CAR-T cell therapy research
- Nanoplatforms for cancer theranostics
- Colorectal Cancer Treatments and Studies
- Computational Drug Discovery Methods
- Blood groups and transfusion
- Cancer therapeutics and mechanisms
- Protein Degradation and Inhibitors
- Glycosylation and Glycoproteins Research
University of South Florida
2021
Dana-Farber Cancer Institute
2021
Pfizer (United Kingdom)
2021
Roche (Switzerland)
2021
Seagen (Canada)
2021
Bristol-Myers Squibb (Germany)
2021
Boehringer Ingelheim (India)
2021
Merck (Germany)
2021
Eterna Therapeutics (United States)
2021
California Institute for Regenerative Medicine
2021
Effective therapies are needed for the treatment of patients with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer (MBC) brain metastases. A trastuzumab radioisotope has been shown to localize in metastases HER2-positive MBC, and intracranial xenograft models have demonstrated a dose-dependent response trastuzumab.
Abstract Background: Efbalropendekin alfa (EBA) is an engineered IL-15/IL-15Rα-Fc fusion protein with optimized potency, designed to improve systemic exposure and pharmacodynamics (PD) while decreasing acute toxicity. It aims enhance anti-tumor immunity via IL-15-mediated signaling on NK cells CD8+ T cells. This first-in-human study evaluated the safety, tolerability, pharmacokinetics (PK), PD, activity of EBA ± atezolizumab (ATZ) in Phase 1a (Ph 1a) Ph 1b. Methods: Patients (pts) aged ≥18...
Abstract The objective of this research was to characterize the venetoclax exposure‐efficacy and exposure‐safety relationships determine its optimal dose in elderly patients with newly diagnosed acute myeloid leukemia (AML) receiving combination low intensity therapies (hypomethylating agent [HMA; azacitidine or decitabine] low‐dose cytarabine [LDAC]). A total 212 from HMA study 92 LDAC were included analyses. Those who received at least one had measurable response (201 83 studies,...
The aim of the study was to characterize population pharmacokinetics (PK) intravenous formulation trastuzumab, assess impact patient and pathological covariates on trastuzumab PK, perform simulations support dosing recommendations in special situations.Serum concentrations were obtained from 1582 patients with metastatic breast cancer (MBC), early (EBC), advanced gastric (AGC), or other tumor types/healthy volunteers 18 phase I, II, III trials analyzed by nonlinear mixed-effects modeling.A...
Abstract Adding pertuzumab to trastuzumab (both monoclonal antibodies targeting human epidermal growth factor receptor 2 [HER2]) has proven survival benefits when combined with chemotherapy for patients HER2‐positive breast cancer. The combination of and together in 1 vial subcutaneous (SC) administration is being developed as a ready‐to‐use formulation reduce the treatment burden on while improving healthcare efficiency. An open‐label, 2‐part, phase Ib dose‐finding study (NCT02738970) was...
Abstract Purpose To characterize pertuzumab pharmacokinetics (PK) in FeDeriCa (NCT03493854: fixed-dose combination of and trastuzumab for subcutaneous injection [PH FDC SC] versus intravenous plus trastuzumab); derive individual exposures the PH SC arm subsequent exposure–response (ER) analyses; compare observed PK with predicted from a previous model; assess whether affects PK; evaluate exposure–efficacy –safety relationships support approved dosing regimen. Methods Population...
C-terminal lysine (CTK) is often classified as a potential critical quality attribute for therapeutic antibodies being developed subcutaneous (SC) administration because of its to impact antibody SC bioavailability/pharmacokinetics (PK). This classification both inflates development costs and increases comparability risks antibodies. However, prior risk assessments CTK have not fully considered biotransformation in the space, which may play an important role given that circulating...
To characterize the pharmacokinetics (PK) of, and perform an exploratory exposure-response (E-R) analysis for, pertuzumab in patients with HER2-positive early breast cancer (EBC) within APHINITY study (NCT01358877, BIG 4-11/BO25126/TOC4939G).A previously developed two-compartment linear population pharmacokinetic (popPK) model was subjected to external validation examine appropriateness for describing concentrations from study. Pharmacokinetic drug-drug interactions (DDIs) between...
To characterize the pharmacokinetics (PK) of pertuzumab and trastuzumab in patients with HER2-positive metastatic gastric or gastroesophageal junction cancer randomized, double-blind, phase III JACOB study (NCT01774786), to evaluate appropriateness regimen these patients. Patients received 840 mg intravenous placebo plus q3w chemotherapy. Pertuzumab were administered until disease progression unacceptable toxicity. Chemotherapy was for up six cycles Serum concentrations measured. PK...
Abstract Background: Intravenous pertuzumab (P IV) + trastuzumab (H chemotherapy (CT) improves outcomes in patients (pts) with HER2-positive breast cancer, compared H CT.A new subcutaneous (SC) formulation, for the first time combining two monoclonal antibodies, P H, recombinant human hyaluronidase one vial, was developed. This ready-to-use fixed-dose combination (PH FDC) is administered subcutaneously into thigh over 5-8 minutes. The dose of SC confirmed phase III HannaH trial (NCT00950300)...
In the APHINITY study (NCT01358877, BIG 4-11/BO25126/TOC4939G), pertuzumab added to trastuzumab and chemotherapy significantly improved invasive disease-free survival as adjuvant treatment for patients with HER2-positive early breast cancer. The objective of this analysis was assess pharmacokinetics in combination Chinese Samples pharmacokinetic were taken from during cycle 1 at steady-state 10. Noncompartmental used estimate minimum maximum serum concentrations (Cmax Cmin), area under...
2525 Background: The aim of this analysis was to develop a PPK model for IV trastuzumab (Herceptin), assess the impact patient covariates on PK, and perform simulations support dosing recommendations. Methods: Serum concentration data (26,040 samples) from 1582 patients with metastatic breast cancer (MBC), early (EBC), advanced gastric (AGC) or other tumor types, 6 healthy volunteers in 18 Phase I, II, III trials were analyzed using nonlinear mixed-effects modeling (NONMEM). Monte Carlo...
PERJETA (pertuzumab), administered with Herceptin (trastuzumab), is used in the treatment of human epidermal growth factor receptor 2-positive breast cancer. Pertuzumab currently approved an initial loading dose 840 mg, followed by a 420-mg maintenance intravenously every 3 weeks. A reloading required if there ≥6-week delay treatment. In response to potential disruption due COVID-19, impact delays and alternative dosing regimens on intravenous pertuzumab for cancer presented. Simulations...
2564 Background: The phase 2a, dose-finding JOSHUA study reported increased P clearance (CL; 37% lower steady-state Cmin [Cmin,ss]) in pts with HER2+ mGEJC/GC vs metastatic breast cancer (MBC). Based on these data, 840 mg q3w was selected for testing the 3 JACOB (NCT01774786) to achieve similar concentrations (conc) BC studies then 420 dose. In JACOB, while there evidence of treatment activity, addition trastuzumab (H) and chemotherapy (CT) 1st-line therapy did not significantly improve...