IDRx Releases Updated Phase 1 Data for IDRX-42 in Advanced GIST at CTOS 2024

IDRx, Inc., a clinical-stage biopharmaceutical company located in Plymouth, Massachusetts, has recently shared updated clinical data from its ongoing Phase 1/1b trial, StrateGIST 1. This trial involves the investigational drug IDRX-42, which is targeted toward patients with advanced gastrointestinal stromal tumors (GIST). The latest data highlight the drug's promising anti-tumor activity and will be presented at the Connective Tissue Oncology Society (CTOS) Annual Meeting in San Diego.

IDRX-42 is an oral, small molecule, tyrosine kinase inhibitor (TKI) specifically designed to target prevalent KIT mutations. These mutations drive tumor growth and lead to resistance against current therapies. Despite the potential of KIT-targeted TKIs, their effectiveness has been limited due to drug resistance and poor tolerability.

Suzanne George, M.D., Chief of the Division of Sarcoma at the Dana-Farber Cancer Institute, noted that the updated data from StrateGIST 1 are highly encouraging. The clinical activity observed in patients with various KIT mutations is promising, and IDRX-42's differentiated profile offers hope for meeting the critical needs of GIST patients.

Tim Clackson, Ph.D., CEO of IDRx, expressed excitement about the emerging durability data from StrateGIST 1. The data support plans to advance IDRX-42 into late-phase development, with a randomized Phase 3 trial, StrateGIST 3, set to evaluate the efficacy and safety of IDRX-42 compared to sunitinib in second-line GIST patients.

As of September 30, 2024, 89 patients with KIT-mutant GIST have been treated with IDRX-42 in the Phase 1 portion of StrateGIST 1, with doses ranging from 120 mg to 1200 mg daily. Among these, 87 patients were evaluable for efficacy. The trial has completed dose escalation and initiated the Phase 1b dose confirmation portion, utilizing a 300 mg tablet formulation.

Patients in the trial had a median of four prior lines of therapy. The overall response rate (ORR) by modified RECIST criteria in the evaluable population was 29%, including one complete response and 24 partial responses. The recommended Phase 1b dose showed an ORR of 26%, with a 53% ORR in second-line patients.

IDRX-42 was generally well tolerated, with treatment-related adverse events mostly being low grade. The most common adverse events included gastrointestinal symptoms and fatigue. The Phase 1b portion of the trial, which began enrollment in May 2024, includes cohorts for first-, second-, and later-line therapies.

Gastrointestinal stromal tumor (GIST) is a prevalent subtype of soft tissue sarcoma in the gastrointestinal tract, with 4,000 to 6,000 new cases diagnosed annually in the United States. Approximately 80% of GIST cases involve KIT mutations. Resistance to current treatments like imatinib remains a significant challenge, highlighting the need for new therapies.

The StrateGIST 1 study aims to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of IDRX-42 in patients with GIST who have progressed on standard therapies. The study is ongoing in multiple countries, including the United States, United Kingdom, Belgium, and others.

IDRX-42 has shown superior anti-tumor activity in pre-clinical studies compared to imatinib and sunitinib, particularly in tumors with KIT mutations. The drug has been granted Fast Track and Orphan Drug designations by the U.S. Food and Drug Administration for treating GIST after progression on imatinib.

IDRx, founded in 2021, focuses on developing precision therapeutics for cancers with well-characterized biology and unmet medical needs. The company's lead program, IDRX-42, aims to improve outcomes for GIST patients and address the limitations of current precision cancer medicines.