PF-06650808 / Pfizer - LARVOL DELTA

Joint Disposition Properties and Comprehensive Pharmacokinetic Characterization of Antibody-Drug Conjugates. (PubMed, AAPS J) - "For instance, the linker stability estimates for PF-06650808, PF-06647020, and PF-06664178 were 0.31, 0.14, and 0.096, respectively, from the JDM-based analyses vs. 0.23, 0.11, and 0.086 by the model-based approach. Additionally, the JDMs were estimated for a number of FDA-approved or otherwise well-documented ADCs, showing their utilities in comparing ADCs in terms of favorable PK characteristics."

Journal • PK/PD data

Antibody-drug conjugate (ADC) joint disposition properties and their clinical utilities for comparative assessments in terms of favorable pharmacokinetic (PK) characteristics. (ASCO 2022) - " The joint disposition metrics representing linker stability (AUCmAb/AUCTab), therapeutic exposure ratio (CLPL/CLADC) and effective drug-antibody ratio (DAR) (AUCCPL/AUCADC), were derived mathematically from a framework of typical ADC designs and verified via modeling approaches using PK data of 3 clinical candidates, an anti-Trop2 ADC (PF-06664178) [King GT, et al. Invest New Drugs 2018;36(5):836-847], an anti-Notch3 ADC (PF-06650808) [Rosen LS, et al. Invest New Drugs 2020;38(1):120-130], and an anti-PTK7 ADC (PF-06647020) [Maitland ML, et al... Three joint disposition metrics were derived for integrated PK characterization of ADCs using conventional PK analytes. Their clinical utilities were explored in assessing among ADCs in terms of favorable PK characteristics. Analyses of additional ADCs may be needed to further validate these metrics for broader usage."

Clinical • PK/PD data • Oncology • NOTCH3

A phase I, dose-escalation study of PF-06650808, an anti-Notch3 antibody-drug conjugate, in patients with breast cancer and other advanced solid tumors. (PubMed, Invest New Drugs) - P1 | "Tumor samples from all responders tested positive for NOTCH3 expression in a retrospective, exploratory analysis. Conclusions The anti-Notch3 ADC PF-06650808 has demonstrated a manageable safety profile and early signs of antitumor activity in patients with advanced BC."

Clinical • Journal • Alopecia • Breast Cancer • Dermatology • Fatigue • HER2 Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Pain • Pruritus • Solid Tumor