A5069542012- Lung Cancer Treatments and Mutations
- Multiple Myeloma Research and Treatments
- Cancer therapeutics and mechanisms
- Acute Lymphoblastic Leukemia research
- Monoclonal and Polyclonal Antibodies Research
- Colorectal Cancer Treatments and Studies
- CAR-T cell therapy research
- Tuberculosis Research and Epidemiology
- HER2/EGFR in Cancer Research
- Lung Cancer Research Studies
- Cancer Genomics and Diagnostics
- Pharmaceutical studies and practices
- Chronic Myeloid Leukemia Treatments
- Acute Myeloid Leukemia Research
- Pharmacological Effects and Toxicity Studies
- Graphene and Nanomaterials Applications
- Advanced Causal Inference Techniques
- Multiple and Secondary Primary Cancers
- Cardiac electrophysiology and arrhythmias
- Synthesis and Biological Activity
- Biosimilars and Bioanalytical Methods
- Bacteriophages and microbial interactions
- Economic and Financial Impacts of Cancer
- Muscle Physiology and Disorders
- Melanoma and MAPK Pathways
Pfizer (United States)
2018-2025
Pfizer (United Kingdom)
2024
University of California, San Francisco
2015-2020
Cytokine release syndrome (CRS) is a common, acute adverse event associated with T‐cell redirecting therapies such as bispecific antibodies (BsAbs). The nature of CRS events data makes it challenging to capture an unbiased exposure–response relationship commonly used models. For example, simple logistic regression models cannot handle traditional time‐varying exposure, and static exposure metrics chosen at early time points lower priming doses may underestimate the incidence CRS. Therefore,...
Objectives: Binimetinib is a reversible inhibitor of mitogen-activated extracellular signal regulated kinase 1 (MEK1) and MEK2 activity approved in combination with encorafenib for the treatment patients unresectable or metastatic melanoma non-small cell lung cancer select BRAF V600 mutations [1]. The primary metabolic pathway accounting binimetinib metabolism glucuronidation via UGT1A1 objectives this analysis were to describe population pharmacokinetics (popPK) evaluate potential...
Objectives: Bispecific antibodies (BsAb) are a rapidly evolving treatment modality for multiple myeloma (MM). Elranatamab, an approved BsAb, forms immune synapse between T-cells via surface marker CD3 and B-cell maturation antigens (BCMA) on tumor cells1. Membrane-bound BCMA can undergo shedding from the cell surface, leading to circulation of soluble (sBCMA), which is associated with disease burden reduces drug exposure may impact efficacy. Establishing recommended dose based non-clinical...
Elranatamab is a BCMA-CD3 bispecific antibody approved for the treatment of relapsed or refractory multiple myeloma. Cytokine release syndrome one most common adverse events associated with antibodies. We aimed to determine optimal elranatamab dosing regimen mitigating cytokine syndrome. Safety, pharmacokinetics, and exposure–response were analyzed across four clinical studies (MagnetisMM-1, MagnetisMM-2, MagnetisMM-3, MagnetisMM-9). Different priming regimens evaluated these included...
Gemtuzumab ozogamicin (Mylotarg; Pfizer, New York, NY) was the first antibody–drug conjugate to be approved for CD 33‐positive acute myeloid leukemia ( AML ). However, it voluntarily withdrawn from US market due lack of clinical benefit in confirmatory phase III trial. In 2012, several investigator cooperative studies using a different dosing regimen showed efficacy, but pharmacokinetic (PK) data were not collected these trials. Through simulation expected concentrations new regimens,...
Lorlatinib is a small molecule inhibitor of anaplastic lymphoma kinase (ALK) and c-ROS oncogene 1 (ROS1) tyrosine kinases approved for the treatment patients with ALK-positive advanced non-small cell lung cancer (NSCLC). In phase I/II study (NCT01970865), potential exposure-response (E-R) relationships between lorlatinib selected safety efficacy end points were evaluated in NSCLC. E-R assessed incidence > 10% all treated (n = 328). total, 4 assessed: hypercholesterolemia grade ≥ 3,...
Abstract Like other monoclonal antibodies, immune checkpoint inhibitors may be immunogenic in some patients, potentially affecting pharmacokinetics (PKs) and clinical outcomes. In post hoc analyses, we characterized antidrug antibody (ADA) development with avelumab monotherapy patients metastatic Merkel cell carcinoma (mMCC) from the JAVELIN 200 trial (first‐line [1L; N = 116] second‐line or later [≥2L; 88] cohorts) advanced urothelial (aUC) Bladder 100 (1L maintenance [ 350]) Solid Tumor...
Dacomitinib is an epidermal growth factor receptor (EGFR) inhibitor approved for the treatment of metastatic non-small cell lung cancer (NSCLC) in first line patients with EGFR activating mutations. taken orally once daily at 45 mg or without food, until disease progression unacceptable toxicity occurs. Oncology often can develop gastroesophageal reflux (GERD), which may require management acid-reducing agent. Proton pump inhibitors (PPIs), such as rabeprazole, inhibit sodium-potassium...
Duchenne muscular dystrophy (DMD) is a rare genetic disorder caused by decreased or absent dystrophin gene leading to progressive muscle degeneration and weakness in young boys. Disease progression models for the North Star Ambulatory Assessment (NSAA), functional measurement widely used assess outcomes clinical trials, were developed using longitudinal population modeling approach. The relationship between NSAA total score over time, loss of ambulation, potential covariates that may...
Aim The aim of this study was to characterize the effect inotuzumab ozogamicin on QT interval in patients with B‐cell malignancies. Methods Data were pooled from three clinical studies including 250 ( n = 2743) who received monotherapy. Patients relapsed/refractory acute lymphoblastic leukaemia (NCT01564784 and NCT01363297) 1.8 mg m −2 per cycle divided doses (mean C max 371 ng ml −1 ; considered therapeutic) non‐Hodgkin lymphoma (NCT00868608) as a single dose 569 supratherapeutic)....
Abstract Purpose Lorlatinib is a third-generation tyrosine kinase inhibitor currently approved for the treatment of anaplastic lymphoma (ALK)-positive metastatic non-small cell lung cancer. This open-label, phase 1, randomized two-sequence, two-treatment, two-period, crossover study investigated absolute oral bioavailability lorlatinib in healthy participants. Methods Eligible participants were to receive two treatments one sequences: 100 mg single dose followed by 50 intravenous (IV) dose,...
Abstract Exposure‐response (E‐R) analyses are an integral component of understanding the benefit/risk profile novel oncology therapeutics. These typically conducted using data from treatment arm to characterize relationship between drug exposure (low vs. high) and efficacy or safety outcomes. For example, outcomes patients with lower in (e.g., Q1) might be compared those higher (Q2, Q3, Q4). Outcomes lowest quartile may also control evaluate whether Q1 subgroup derived clinical benefit....
Abstract BACKGROUND: Avelumab, a monoclonal antibody targeting PD-L1, is currently approved in the USA combination with axitinib for first-line treatment of patients aRCC. This analysis evaluated relationship between potential covariates, including avelumab exposure, and efficacy endpoints progression-free survival (PFS; by blinded independent central review per Response Evaluation Criteria Solid Tumors [RECIST] criteria) objective response (OR; RECIST) METHODS: Exposure metrics all JAVELIN...