Phase 1 clinical trial underway evaluating QTX3046, a novel orally bioavailable and brain-penetrant, non-covalent allosteric G12D-selective-KRAS dual (OFF/ON)-state inhibitor, in patients with KRASG12D-mutated advanced solid tumors
First patient dosed with QTX3034, G12D-preferring oral multi-KRAS inhibitor, and EGFR inhibitor cetuximab in the combination portion of ongoing Phase 1 dose escalation in patients with KRASG12D-mutated colorectal cancer
GLP toxicology studies initiated for QTX3544, G12V-preferring oral multi-KRAS inhibitor, to support an anticipated IND filing in 4Q 2024
June 27, 2024
RADNOR, Pa. & SOUTH SAN FRANCISCO, Calif.; June 27, 2024 — Quanta Therapeutics, a privately-held clinical-stage biopharmaceutical company leading the development of innovative, oral therapeutics for RAS-driven cancers, announced the advancement of two clinical trials from its pipeline of KRAS-directed drug candidates. The first patient has been dosed in the monotherapy portion of a Phase 1 clinical trial evaluating QTX3046, a KRASG12D-selective inhibitor, and patient dosing has begun in the combination portion of the ongoing Phase 1 clinical trial assessing QTX3034, G12D-preferring multi-KRAS inhibitor, and cetuximab. Both clinical trials are enrolling patients with KRASG12D-mutated advanced solid tumors. Quanta has also initiated GLP toxicology studies for QTX3544, its G12V-preferring KRAS inhibitor, that will support an investigational new drug (IND) submission anticipated in the fourth quarter of 2024.
“We are pleased to now have two KRAS inhibitor programs in the clinic focused on treating G12D-mutated cancers,” said Leonardo Faoro, MD, MBA, Chief Medical Officer of Quanta Therapeutics. “The combination treatment with KRAS and EGFR inhibitors has shown promising efficacy in multiple KRASG12C-mutated tumor types. In order to achieve similar breakthroughs against the more prevalent G12D mutation, it will require oral small molecules with direct inhibition of the target and properties enabling use in combination treatments. We believe we are leading the field with the combination of oral, direct inhibition of KRASG12D and EGFR antibody therapy for difficult-to-treat solid tumors.”
“The Quanta team continues to make progress advancing our pipeline of novel KRAS inhibitors with chemically-distinct candidates targeting G12D and G12V,” said Perry Nisen, MD, PhD, Chief Executive Officer of Quanta. “With potentially best-in-class profiles for RAS-driven cancers, these drug candidates leverage our proprietary research and translational platform and are well positioned to address the significant unmet need for patients with KRAS-mutated cancer beyond G12C.”
Quanta’s lead programs are two chemically-distinct non-covalent, potent, orally bioavailable, allosteric clinical candidates targeting KRASG12D-mutated cancers. QTX3034 is a multi-KRAS inhibitor with G12D-preferring activity. QTX3046 is a KRASG12D-selective inhibitor. Both Phase 1 clinical trials are enrolling patients with KRASG12D mutations in dose escalation cohorts as monotherapy and in combination with cetuximab. Dose expansion cohorts will consist of patients with KRASG12D-mutant pancreatic, colorectal, lung, and endometrial cancers. Endpoints include safety and tolerability, determination of the maximum tolerated dose/recommended Phase 2 dose, pharmacokinetic properties, antitumor activity, and molecular markers. The clinical trials are being conducted at clinical sites in the US. More information about the QTX3034 clinical trial (NCT06227377) and the QTX3046 clinical trial (NCT06428500) can be found on https://clinicaltrials.gov/.
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).
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; QTX3544, a multi-KRAS inhibitor with G12V-preferring activity (G12V+ multi-KRAS) projected to submit IND in 4Q 2024. Quanta is headquartered in South San Francisco, CA, and has a site in Radnor, PA.
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Quanta Therapeutics
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