Virtual clinical trial simulations for a novel KRASG12C inhibitor (ASP2453) in non-small cell lung cancer
Collaboration with Astellas Pharma - Published in CPT: Pharmacometrics & Systems Pharmacology
Model-Informed Drug Development of the Masked Anti-PD-L1 Antibody CX-072
Collaboration with CytomX Therapeutics - Published in Clinical Pharmacology & Therapeutics
Abstract
CX‑072 is an anti‑PD‑L1 (programmed death ligand 1) Probody therapeutic (Pb‐Tx) designed to be preferentially activated by proteases in the tumor microenvironment and not in healthy tissue. Here, we report the model‐informed drug development of CX‐072. A quantitative systems pharmacology (QSP) model that captured known mechanisms of Pb‐Tx activation, biodistribution, elimination, and target engagement was used to inform clinical translation.
Phase 1 Safety of ICOS Agonist Antibody JTX-2011 Alone and with Nivolumab in Advanced Solid Tumors
Collaboration with Jounce - Presented at ASCO Annual Meeting 2017
Overview
In this collaboration with Jounce Therapeutics, we developed a quantitative systems pharmacology (QSP) model describing target binding by JTX-2011 and target mediated drug disposition in blood, tumor and non-tumor tissues based on preclinical potency and non-linear PK data across species. The model was translated to predict PK and target engagement (TE) in humans to facilitate dose selection. The QSP model predicted >95% TE for 21 days at the top planned dose.
Mechanistic Quantitative Pharmacology Strategies for the Early Clinical Development of Bispecific Antibodies in Oncology
Abstract
Bispecific antibodies (bsAbs) have become an integral component of the therapeutic research strategy to treat cancer. In addition to clinically validated immune cell re‐targeting, bsAbs are being designed for tumor targeting and as dual immune modulators. Explorative preclinical and emerging clinical data indicate potential for enhanced efficacy and reduced systemic toxicity.
Mechanistic PKPD Models of Protein Therapeutics for Early Clinical Development
Abstract
Mechanistic PKPD models support FIH trial design, development of targeted immunotherapies, and understanding complex PK properties and covariates.
Computational Exploration of ADC Pharmacokinetics
Abstract
The pharmacokinetics of antibody drug conjugate (ADC) therapeutics typically show a discrepancy between the PK of total antibody (conjugated and unconjugated antibody) and that of conjugated antibody, carrying one or more payload molecules. This discrepancy is often attributed to deconjugation (Kamath, 2014), however recent evidence suggests that the underlying mechanisms may be more complex.
Non-clinical Studies to Clinical Design Using QSP Model of T Cell Engaging Bispecifics
Collaboration with Pfizer - Presented at AAPS 2019 PharmSci 360
Modeling to Support Dose Justification for Anti-PD-L1 Clinical Candidate CK-301 in Oncology Patients
Collaboration with Checkpoint Therapeutics - Presented at SITC Annual Meeting 2019
Abstract
Background: Mathematical modeling was used in conjunction with in vitro, preclinical and clinical data to facilitate dose selection of CK-301 (also known as TG-1501), an anti-PD-L1 monoclonal antibody (mAb), for ongoing and future clinical trials in oncology patients.