A phase 1 trial evaluating the safety, tolerability, PK, and preliminary efficacy of QTX3034, an oral G12D-preferring multi-KRAS inhibitor, in patients with solid tumors with KRASG12D mutation
Abstract
TPS3172 Background: KRAS is one of the most mutated driver oncogenes across solid tumors, and KRAS G12D missense mutations have high prevalence in pancreatic, colorectal (CRC), and endometrial cancers. QTX3034 is a highly-selective, non-covalent, orally bioavailable, multi-KRAS inhibitor with potent activity across several KRAS variants, particularly G12D. QTX3034 binds to GDP-bound forms of mutant and wild-type KRAS with (sub)nanomolar affinities, allosterically inhibiting its conversion to the active state. QTX3034 inhibits KRAS signaling in in vitro studies and displays synergy with EGFR inhibitors. In vivo evaluation of QTX3034 resulted in significant tumor growth inhibition across various tumor models, with tumor regressions observed in 100% of animals in both HPAC pancreatic and GP2D colorectal KRAS G12D xenograft models. QTX3034 exhibits brain penetration in preclinical studies, including an orthotopic model of intracranial efficacy. This clinical trial is now enrolling patients with advanced solid tumors harboring a KRASG12D mutation. Methods: This is a first-in-human, multicenter, open-label phase 1 study in adult patients with advanced solid tumors with KRASG12D mutations, without prior direct KRAS inhibitor treatment (NCT06227377). The primary objectives are to evaluate the safety and tolerability and to determine maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of QTX3034 alone, and in combination with cetuximab. Secondary objectives are…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 30 participants or records.
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