Publications by authors named "Anita Moein"

Purpose: Among cases of breast cancer, estrogen receptor-positive (ER +), PIK3CA-mutant, HER2- advanced breast cancer stands as a particularly complex clinical indication where approximately 40% of ER + /HER2- breast carcinomas present mutations in the PIK3CA gene. A significant hurdle in treating ER + breast cancer lies in surmounting the challenges of endocrine resistance. In the clinical setting, a multifaceted approach is essential for this indication, one that not only explores the effectiveness of individual treatments but also delves into the potential gains in therapeutic outcome from combination therapies.

View Article and Find Full Text PDF

Background And Objectives: Despite significant progress in biomedical research, the rate of success in oncology drug development remains inferior to that of other therapeutic fields. Mechanistic models provide comprehensive understanding of the therapeutic effects of drugs, which is crucial for designing effective clinical trials. This study was performed to acquire a better understanding of PI3K-AKT-TOR pathway modulation and preclinical to clinical translational bridging for a specific compound, apitolisib (PI3K/mTOR inhibitor), by developing integrated mechanistic models.

View Article and Find Full Text PDF

Cancer remains a significant global health challenge, and despite remarkable advancements in therapeutic strategies, poor tolerability of drugs (causing dose reduction/interruptions) and/or the emergence of drug resistance are major obstacles to successful treatment outcomes. Metastatic renal cell carcinoma (mRCC) accounts for 2% of global cancer diagnoses and deaths. Despite the initial success of targeted therapies in mRCC, challenges remain to overcome drug resistance that limits the long-term efficacy of these treatments.

View Article and Find Full Text PDF

The Mayo Clinical Score is used in clinical trials to describe the clinical status of patients with ulcerative colitis (UC). It comprises four subscores: rectal bleeding (RB), stool frequency (SF), physician's global assessment, and endoscopy (ENDO). According to recent US Food and Drug Administration guidelines (Ulcerative colitis: developing drugs for treatment, Guidance Document, https://www.

View Article and Find Full Text PDF

Inappropriate and chronic activation of the cytosolic NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome, a key component of innate immunity, likely underlies several inflammatory diseases, including coronary artery disease. This first-in-human phase I trial evaluated safety, pharmacokinetics (PKs), and pharmacodynamics (PDs) of oral, single (150-1800 mg) and multiple (300 or 900 mg twice daily for 7 days) ascending doses (SADs and MADs) of GDC-2394, a small-molecule inhibitor of NLRP3, versus placebo in healthy volunteers. The study also assessed the food effect on GDC-2394 and its CYP3A4 induction potential in food-effect (FE) and drug-drug interaction (DDI) stages, respectively.

View Article and Find Full Text PDF

Etrolizumab is an IgG1-humanized monoclonal antibody that specifically targets the β7 subunit of α4β7 and α4Eβ7 integrins, and it has been evaluated for the treatment of moderately-to-severely active ulcerative colitis (UC). Population pharmacokinetic (PK) analysis was performed to characterize etrolizumab PK properties in patients with moderately-to-severely active UC and evaluate covariate impacts on exposure. The population PK model was developed based on etrolizumab serum concentrations from patients with moderately-to-severely active UC enrolled in six studies (one phase I, one phase II, and four phase III) and validated using another phase III clinical trial.

View Article and Find Full Text PDF

Etrolizumab is an IgG1-humanized monoclonal anti-β7 integrin antibody. Phase III trials with induction and/or maintenance phases were conducted in patients with moderately-to-severely active ulcerative colitis (UC) who were either previously treated with tumor necrosis factor (TNF) inhibitors (HICKORY) or were TNF inhibitor naïve (HIBISCUS I/II, LAUREL, and GARDENIA). A total of eight exposure-response analyses were conducted for two clinical outcomes (remission and endoscopic improvement) at the end of induction for studies HIBISCUS I/II (combined) and HICKORY and at the end of maintenance for studies HICKORY and LAUREL.

View Article and Find Full Text PDF

Compared with intravenous formulations, subcutaneous (s.c.) formulations of therapeutic monoclonal antibodies may provide increased patient access and more convenient administration options, although historically high-volume s.

View Article and Find Full Text PDF

Background: Crenezumab, a fully humanized anti-beta-amyloid (Aβ) immunoglobulin G4 (IgG4) monoclonal antibody, binds to both monomeric and aggregated forms of Aβ. We assessed the pharmacokinetics (PK)/pharmacodynamics (PD) of crenezumab and its interaction with monomeric Aβ(1-40) and Aβ(1-42) peptides in serum/plasma and cerebrospinal fluid (CSF) samples from the phase II ABBY and BLAZE studies and the phase Ib GN29632 study.

Methods: In ABBY, BLAZE, and GN29632 studies, patients with mild-to-moderate AD were treated with either placebo or crenezumab (300 mg subcutaneously every 2 weeks [q2w], or 15 mg/kg, 30 mg/kg, 45 mg/kg, 60 mg/kg, or 120 mg/kg intravenously q4w).

View Article and Find Full Text PDF

GDC-0853 is a small molecule inhibitor of Bruton's tyrosine kinase (BTK) that is highly selective and noncovalent, leading to reversible binding. In double-blind, randomized, and placebo-controlled phase I healthy volunteer studies, GDC-0853 was well tolerated, with no dose-limiting adverse events (AEs) or serious AEs. The maximum tolerated dose was not reached during dose escalation (≤600 mg, single ascending dose (SAD) study; ≤250 mg twice daily (b.

View Article and Find Full Text PDF