IDRx Updates Phase 1 Data on IDRX-42 for GIST Patients

IDRx, Inc., a clinical-stage biopharmaceutical company focused on innovative cancer treatments, has revealed promising preliminary data from the Phase 1 segment of its ongoing StrateGIST 1 study. This study involves IDRX-42, a novel tyrosine kinase inhibitor (TKI) targeting advanced gastrointestinal stromal tumors (GIST) with KIT mutations. The findings will be presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

IDRX-42 is designed to address both the activating mutations and a range of resistance mutations found in KIT-driven GIST. This new therapy aims to overcome the limitations of existing TKIs, which often fail to provide long-lasting responses or come with significant adverse effects. According to Professor Patrick Schöffski, M.D., M.P.H., of University Hospitals Leuven, IDRX-42 shows significant potential in fulfilling the unmet needs for next-generation GIST therapies.

Key findings from the study, as of April 28, 2024, include data on 73 patients treated across various dose cohorts, ranging from 120 mg once daily to 600 mg twice daily. All patients had KIT-mutant GIST, and 66 were evaluable for efficacy. Notably, dose escalation did not reach a maximum tolerated dose, and the trial has moved into the Phase 1b dose confirmation stage using a 300mg tablet formulation.

Patients in the study were heavily pretreated, with many having undergone multiple prior lines of therapy. Specifically, 19% had received one prior line, 11% had two prior lines, and 70% had three or more. Despite this, 74% of the participants remained on study treatment, with a median treatment duration of 16 weeks. All second-line patients continued treatment at the time of data cut-off.

The objective response rate (ORR) was noteworthy. Across all lines of therapy, the ORR was 23%, with all responses being partial. Among second-line patients, the ORR was even higher at 43%. Additionally, reductions in the mutant allele fraction of circulating tumor DNA (ctDNA) were consistently observed, indicating the drug's efficacy against both activating and resistance mutations.

Regarding safety, IDRX-42 exhibited a favorable profile. The most common treatment-related adverse events (TRAEs) were low-grade gastrointestinal symptoms and fatigue. Dose modifications due to TRAEs were rare, with only 6% dose reductions and 9% dose interruptions at the 400 mg daily dose level. No discontinuations due to TRAEs were reported.

Dose-limiting toxicities (DLTs) were found in three patients at higher doses (600 mg, 800 mg, and 1200 mg). All three patients chose to reduce their dose and continued in the study, with two achieving partial responses at a reduced dose of 400 mg daily.

IDRx’s CEO, Tim Clackson, Ph.D., emphasized that these preliminary results underscore IDRX-42's potential as a best-in-class treatment for GIST. He highlighted plans to advance the drug into earlier lines of therapy, a sentiment echoed by David Kerstein, M.D., Chief Medical Officer of IDRx. Dr. Kerstein noted the drug's promising activity and manageable safety profile, which includes a notable lack of adverse events typically associated with off-target effects.

The StrateGIST 1 study aims to further evaluate IDRX-42’s safety, tolerability, pharmacokinetics, and preliminary antitumor activity in patients with advanced GIST, particularly those resistant to prior TKI treatments. This study is ongoing at multiple sites, including locations in the U.S. and Europe.

IDRX-42 is a highly selective KIT inhibitor that has demonstrated superior antitumor activity in preclinical models compared to currently approved therapies. The company, founded in 2021, focuses on developing precision therapies designed to counteract tumor escape mechanisms and extend the duration of response to treatment. IDRx’s pipeline also includes another KIT inhibitor, IDRX-73.

In summary, IDRX-42 shows substantial promise for treating GIST, with early data suggesting significant efficacy and a manageable safety profile. The company is poised to continue its development, aiming to offer new hope for patients with this challenging cancer.