LR26007 / Frontier Medicines, LG Chem - LARVOL DELTA

A Study of LG00313112 in Participants With Advanced Solid Malignancies Harboring a TP53 Y220C Mutation (clinicaltrials.gov) - P1/2 | N=250 | Not yet recruiting | Sponsor: LG Chem

First-in-human • New P1/2 trial • P53mut • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Estrogen Receptor Positive Breast Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Small Cell Lung Cancer • Solid Tumor • TP53

LG Chem secures FDA clearance for phase 1/2 trial of TP53-mutant solid tumor drug candidate (Korea Biomedical Review) - "The company said Tuesday that it has received clearance from the U.S. Food and Drug Administration (FDA) to initiate a phase 1/2 clinical trial of its investigational anticancer drug candidate, LG00313112...The phase 1 portion will evaluate the safety, tolerability, recommended phase 2 dose, and preliminary efficacy of LG00313112 in patients with advanced solid tumors carrying the TP53 Y220C mutation, including ovarian, lung, and breast cancers. The subsequent phase 2 study will further assess the drug's efficacy based on the phase 1 findings."

IND • New P1 trial • P53mut • Breast Cancer • Lung Cancer • Ovarian Cancer • Solid Tumor

Restoring the function of the guardian of the genome: FMC-220 a highly potent and selective covalent activator of p53 Y220C (AACR 2025) - "In contrast to reversible Y220C binders including rezatapopt, covalent engagement of Y220C results in persistent activation of p53 following drug washout that leads to enhanced Y220C mutant cancer cell senescence and death. In addition, FMC-220 is very well tolerated in vivo. Together, these data demonstrate the promise of FMC-220, a first-in-class covalent activator of p53 Y220C, with the potential to deliver improved outcomes for patients with Y220C mutation positive tumors."

Oncology • KRAS • TP53

FMC-220, a highly potent and selective covalent activator of p53 Y220C, is broadly active in p53 Y220C containing PDX models across cancer indications (AACR-NCI-EORTC 2025) - "ChIPseq analysis demonstrated that FMC-220 delivers far more durable activation and ​persistent engagement of target gene promoters than noncovalent strategies such as rezatapopt (PC14586). In addition, FMC-220 combines effectively with other therapeutics including MDM2 inhibitors or DNA damaging agents. Together, these data demonstrate the promise of FMC-220, a first-in-class covalent activator of p53 Y220C, with the potential to deliver improved outcomes for patients with Y220C mutation positive tumors."

Oncology • KRAS • TP53

Frontier Medicines Unveils New Preclinical Data for FMC-220, a First-in-Class Covalent p53 Y220C Activator, at AACR 2025 (GlobeNewswire) - "Preclinical studies showed FMC-220 delivers unprecedented potency, selective engagement, and durable anti-tumor activity at low doses across a broad range of tumor models, including those harboring co-mutations such as those in KRAS. The company plans to file an Investigational New Drug (IND) application for FMC-220 in the second half of 2025."

IND • Preclinical • Solid Tumor

Frontier Medicines Announces FMC-220, the First Covalent p53 Y220C Activator Development Candidate, with Best-in-Class Potential (GlobeNewswire) - "Frontier Medicines...announced the selection of FMC-220, the first covalent p53^Y220C activator designed to overcome the limitations of potency and durability seen in non-covalent approaches...Preclinical studies demonstrate that FMC-220 delivers unprecedented potency and durable anti-tumor activity both in vitro and in vivo, achieving pronounced tumor regression at low doses. This innovative drug candidate leverages a covalent design to deliver prolonged target engagement, driving durable activation of p53 function inducing tumor cell senescence and importantly, cell death....FMC-220 in patients with solid tumors and other cancers are ongoing, with a planned Investigational New Drug (IND) application submission to the U.S. Food and Drug Administration (FDA) in the second half of 2025."

IND • New molecule • Preclinical • Solid Tumor