Quanta Therapeutics Presents Late-Breaking Data for QTX3544, an Oral G12V-Preferring Multi-KRAS Inhibitor, at AACR Annual Meeting 2025
- Preclinical data demonstrates synergy of QTX3544 with EGFR inhibitors, broadly enhancing anti-tumor activity -
- Data supports ongoing Phase 1 clinical trial for QTX3544 as monotherapy and in combination with cetuximab in patients with KRASG12V mutations -
SOUTH SAN FRANCISCO, Calif., April 28, 2025 (GLOBE NEWSWIRE) -- Quanta Therapeutics, a privately-held clinical-stage biopharmaceutical company leading the development of innovative, oral therapeutics for RAS-driven cancers, today announced late-breaking preclinical data for QTX3544, an oral, G12V-preferring, dual ON/OFF state, multi-KRAS inhibitor currently being evaluated in a Phase 1 clinical trial in patients with KRASG12V mutation. Data are being presented at the American Association for Cancer Research (AACR) Annual Meeting 2025 being held April 25-30, 2025, in Chicago, Illinois.
“There is a high unmet need for effective treatments in KRASG12V-mutated cancers, the second most prevalent in KRAS-driven cancers, for which there are no current targeted treatments, including colorectal and pancreatic cancers. Using a clinically validated approach against G12C mutations, we aim to combine allosteric KRAS inhibition and EGFR blockade to enhance the depth and durability of tumor response against G12V,” said Leonardo Faoro, MD, MBA, Chief Medical Officer of Quanta Therapeutics. “QTX3544 has shown high potency against multiple KRAS variants, particularly G12V. These preclinical data support the clinical strategy to combine QTX3544 and cetuximab to enhance the therapeutic activity against KRASG12V-driven cancers. We look forward to evaluating this combination in the ongoing Phase 1 clinical trial.”
“We continue to generate promising data supporting our unique pipeline of KRAS-directed agents, as we advance three distinct candidates in the clinic targeting high prevalence KRAS mutations across solid tumors with major unmet need. QTX3034 and QTX3046 are being developed for G12D-mutant and QTX3544 for G12V-mutant KRAS-driven cancers,” said Perry Nisen, MD, PhD, Chief Executive Officer of Quanta. “We are building a compelling clinical package across our three lead programs and are on track to share proof-of-concept data later this year as our pipeline continues to progress.”
Studies evaluating the potential synergy between QTX3544 and EGFR inhibitors (afatinib and cetuximab) in KRASG12V-driven cancer cell lines and tumor models demonstrated:
- QTX3544 synergized with EGFR inhibitors and potently inhibited KRASG12V-mutant cell proliferation in cell viability assays.
- Combined treatment of QTX3544 with afatinib led to a deeper suppression of MAPK signaling and enhanced inhibition of KRASG12V-driven cancer cell survival in colony formation assays.
- Combination treatment of QTX3544 with cetuximab significantly enhanced anti-tumor efficacy and elicited greater tumor regressions in pancreatic and colorectal KRASG12V-mutant cell line-derived xenograft models, as well as in a patient-derived colorectal tumor xenograft model.
AACR presentation information:
Title: QTX3544, a potent and selective G12V-preferring KRAS inhibitor, synergizes with EGFR inhibitors for enhanced anti-tumor activity
Date and Time: Wednesday, April 30, 2025; 9:00 AM - 12:00 PM
Session Name: Late-Breaking Research: Experimental and Molecular Therapeutics 4
Abstract Number: LB430
Location: Poster Section 51
About QTX3544
QTX3544 is an allosteric, G12V-preferring multi-KRAS inhibitor. The QTX3544 Phase 1 clinical trial is initially enrolling patients with KRASG12V mutation in dose escalation cohorts as monotherapy and in combination with cetuximab. The Phase 1 clinical endpoints include safety and tolerability, determination of the maximum tolerated dose/recommended Phase 2 dose, pharmacokinetic properties, anti-tumor activity, and molecular markers. The clinical trial is being conducted at clinical sites in the US. More information about the QTX3544 clinical trial (NCT06715124) can be found on https://clinicaltrials.gov/.
About RAS and the MAPK Pathway
The mitogen-activated protein kinase (MAPK) pathway is a central signaling cascade that regulates cellular growth, proliferation, differentiation, and survival. When one of the proteins in the pathway is mutationally activated, it can drive tumor development and growth. RAS is the most frequently mutated oncogene in cancer, with KRAS mutations occurring in nearly one-quarter of all human cancers. RAS mutations impair the ability of RAS to convert from its active GTP-bound “ON” form into its inactive GDP-bound “OFF” state, leading to the sustained activation of the MAPK signaling pathway and ultimately driving tumorigenesis. KRAS mutations, especially G12D, G12V, and G12C, are highly prevalent in pancreatic, colorectal, and lung cancers. First-generation KRAS inhibitors have demonstrated clinical benefit, but their impact is limited to a subset of patients with a single type of KRAS mutation (G12C).
About Quanta Therapeutics
Quanta Therapeutics is a private biopharmaceutical company focused on the most prevalent and elusive target in oncology—RAS. Our vision is to develop novel small molecule cancer medicines by selectively targeting protein-protein interactions that are key to oncogenic RAS activity. Driving Quanta's success is our unique high-throughput platform that applies Second Harmonic Generation (SHG) optical technology to identify allosteric modulators of protein complexes. The Quanta team has extensive drug development expertise and substantial research experience in the RAS space. By applying innovative medicinal chemistry and its unique protein conformation detection technology, Quanta aims to advance differentiated, next-generation RAS programs that address the resistance paradigms of targeted therapy in oncology. Quanta’s KRAS inhibitor pipeline includes three programs: QTX3034, a multi-KRAS inhibitor with G12D-preferring activity (G12D+ multi-KRAS), currently in a Phase 1 clinical trial as monotherapy and in combination with cetuximab; QTX3046, a G12D-selective KRAS inhibitor, currently in a Phase 1 clinical trial as monotherapy and in combination with cetuximab; QTX3544, a multi-KRAS inhibitor with G12V-preferring activity (G12V+ multi-KRAS) currently in a Phase 1 clinical trial as a monotherapy and in combination in patients with KRASG12V-driven solid tumors. Quanta is headquartered in South San Francisco, CA, and has a site in Radnor, PA. Find more information at https://www.quantatx.com/. Follow us on LinkedIn: Quanta Therapeutics.
CONTACT: Quanta Therapeutics Heather Meeks 661-992-6907 heather.meeks@quantatx.com Media Contact Kelli Perkins kelli@redhousecomms.com
