PF-06263507 / Pfizer - LARVOL DELTA

Phase I dose escalation trial to evaluate safety and preliminary efficacy of ACR246, an innovative 5T4- antibody drug conjugate (ADC), in patients (pts) with advanced solid tumors (ESMO 2024) - P1 | "Previously, several 5T4-ADCs were developed and advanced to phase 1 clinical trials, including PF-06263507, ASN004 and SYD1875. Dose limiting toxicity (DLT) will be assessed at each dose level. The DLT evaluation period will be 21 days."

Clinical • Metastases • P1 data • Oncology • Solid Tumor • TPBG

[VIRTUAL] Introduction to the preclinical profile of SYD1875, a novel site-specifically conjugated duocarmycin-based 5T4-targeting antibody-drug conjugate (AACR 2021) - P1 | "SYD1875 showed superior in vitro cytotoxicity and in vivo activity compared to A1-mcMMAF -also known as PF-6263507-, a 5T4-targeting ADC that is no longer in clinical development. The GLP toxicity study in cynomolgus monkey showed an acceptable toxicity and PK profile. A first-in-human dose-finding trial was initiated to evaluate safety and explore efficacy (NCT04202705)."

Preclinical • Oncology • TPBG

ASN004, a 5T4-targeting scFv-Fc antibody-drug conjugate with high drug-to-antibody ratio, induces complete and durable tumor regressions in preclinical models. (PubMed, Mol Cancer Ther) - "In head-to-head studies, superior activity of ASN004 was demonstrated against trastuzumab-DM1, in a low-5T4/high-HER2 expressing gastric tumor model, and 10-fold greater potency was found for ASN004 against the 5T4-targeted ADC PF-06263507 in a lung tumor model. In marmoset monkeys, ASN004 was well tolerated at doses up to 1.5 mg/kg Q3W iv, and showed dose-dependent exposure, linear pharmacokinetics, and markedly low exposure of free payload drug. Taken together, these findings identify ASN004 as a promising new ADC therapeutic for clinical evaluation in a broad range of solid tumor types."

Journal • Preclinical • Cervical Cancer • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Solid Tumor • HER-2 • TPBG

Pfizer pipeline: As of July 28, 2015 (Pfizer Press Release) - Projects Discontinued from Development since April 28, 2015: [1] PF-03084014 (Gamma-Secretase Inhibitor) in Triple Negative Breast Cancer; [2] PD-0325901 in Cancer (in combination with PF-05212384); [3] PF-06263507 in Cancer (Biologic)."

Discontinued • Breast Cancer • Oncology