PF-06952229 / Pfizer - LARVOL DELTA

Nonclinical Profile of PF-06952229 (MDV6058), a Novel TGFβRI/Activin Like Kinase 5 (ALK-5) Inhibitor Supports Clinical Evaluation in Cancer. (PubMed, J Pharmacol Exp Ther) - "Additionally, a nonclinical toxicology package without cardiovascular liabilities and generally monitorable toxicity profile has been completed. The compound presents an acceptable ICHS9 compliant profile for the intended-to-treat cancer patients."

Journal • Cardiovascular • Colon Cancer • Colorectal Cancer • Hematological Disorders • Oncology • Solid Tumor • TGFB1 • TGFBR1

PF-06952229, a selective TGF-β-R1 inhibitor: preclinical development and a first-in-human, phase I, dose-escalation study in advanced solid tumors. (PubMed, ESMO Open) - P1 | "Antitumor activity of PF-06952229 was observed in preclinical studies. PF-06952229 was generally well tolerated with manageable toxicity; a small group of patients achieved durable responses and/or disease stabilization."

Journal • Metastases • P1 data • Preclinical • Cardiovascular • Genito-urinary Cancer • Hematological Disorders • Hypertension • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • TGFB1

Discovery of MDV6058 (PF-06952229), a Selective and Potent TGFβR1 Inhibitor: Design, Synthesis and Optimization. (PubMed, Bioorg Med Chem Lett) - "A solvent-exposed part of this molecule was used to analogue and modulate cell activity, liver microsome stability and mouse pharmacokinetics. The evolution of SAR that led to the selection of 2 (MDV6058 / PF-06952229) as a preclinical lead compound is described."

Journal • Oncology • TGFB1 • TGFBR1

PF-06952229 Treatment in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=49 | Terminated | Sponsor: Pfizer | Completed ➔ Terminated; The decision to stop enrollment was due to strategic considerations and not due to any specific safety reasons or request from a regulatory authority.

Trial termination • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Liver Cancer • Lung Cancer • Melanoma • Mesothelioma • Oncology • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

PF-06952229 Treatment in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=49 | Completed | Sponsor: Pfizer | Active, not recruiting ➔ Completed

Trial completion • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Liver Cancer • Lung Cancer • Melanoma • Mesothelioma • Oncology • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

PF-06952229 Treatment in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=47; Active, not recruiting; Sponsor: Pfizer; Recruiting ➔ Active, not recruiting; N=90 ➔ 47

Enrollment change • Enrollment closed • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Liver Cancer • Lung Cancer • Melanoma • Mesothelioma • Oncology • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • MRI

PF-06952229 Treatment in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=90; Recruiting; Sponsor: Pfizer; Trial completion date: Jun 2025 ➔ Apr 2022; Trial primary completion date: Aug 2023 ➔ Apr 2022

Clinical • Trial completion date • Trial primary completion date • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Liver Cancer • Lung Cancer • Melanoma • Mesothelioma • Oncology • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • MRI

PF-06952229 Treatment in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=105; Recruiting; Sponsor: Pfizer; Trial completion date: Aug 2023 ➔ Dec 2024

Clinical • Trial completion date • Breast Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Prostate Cancer • Solid Tumor • HER-2

PF-06952229 Treatment in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=100; Recruiting; Sponsor: Pfizer; Trial completion date: Sep 2024 ➔ Aug 2023

Clinical • Trial completion date • Breast Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Prostate Cancer • Solid Tumor • HER-2

PF-06952229 Treatment in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=100; Recruiting; Sponsor: Pfizer; Trial completion date: Jun 2024 ➔ Sep 2024; Trial primary completion date: Aug 2022 ➔ Nov 2022

Clinical • Trial completion date • Trial primary completion date • HER-2

PF-06952229 Treatment in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=100; Recruiting; Sponsor: Pfizer; Active, not recruiting ➔ Recruiting; N=15 ➔ 100

Clinical • Enrollment change • Enrollment open • HER-2

PF-06952229 Treatment in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=15; Active, not recruiting; Sponsor: Pfizer; Recruiting ➔ Active, not recruiting; N=100 ➔ 15; Trial completion date: Oct 2023 ➔ Feb 2024; Trial primary completion date: Dec 2021 ➔ Apr 2022

Clinical • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date