Rgenta Therapeutics has announced the dosing of the first patients in its Phase 1a/b clinical trial of RGT-61159, a novel oral small molecule targeting MYB for the treatment of advanced adenoid cystic carcinoma (ACC) and colorectal cancer (CRC). This first-in-human study aims to evaluate the safety, tolerability, pharmacokinetics, and target engagement of RGT-61159 in patients with relapsed or refractory ACC or CRC.
Targeting MYB in Advanced Cancers
RGT-61159 is designed to modulate the splicing of the transcription factor MYB, leading to the inhibition of oncogenic MYB protein production. Aberrant MYB expression is implicated in various cancers, including ACC, AML, T-ALL, CRC, SCLC, and breast cancer. In ACC, overactivation of the MYB oncogene is a hallmark, present in over 90% of cases. Similarly, MYB is significantly overexpressed in 80-85% of CRC cases, correlating with tumor aggressiveness and poor prognosis.
Clinical Trial Details
The Phase 1a/b trial is a multi-center, open-label study involving dose escalation and expansion in patients with advanced relapsed or refractory ACC or CRC. The study's primary objectives include assessing the safety and tolerability of RGT-61159, while secondary objectives involve evaluating pharmacokinetics, target engagement, and preliminary clinical efficacy. Additional trial details are available at ClinicalTrials.gov (NCT06462183).
Unmet Medical Needs in ACC and CRC
ACC is a rare and aggressive malignancy, affecting an estimated 200,000 people worldwide, with approximately 11,000 cases in the US. Treatment options are limited, often involving surgery and/or radiation, which frequently fail to control local recurrence and distant metastases. There are currently no effective targeted therapies available for patients with recurrent and/or metastatic ACC.
CRC is the third most prevalent cancer and the second leading cause of cancer-related mortality globally, with over 1.9 million cases diagnosed in 2022. Despite advances in early detection and targeted therapies, a significant proportion of patients present with or develop metastases, leading to poor outcomes, especially in those who have exhausted standard-of-care options.
Expert Commentary
"Currently, there are no effective systemic treatment options for ACC. Patients with this rare and aggressive cancer, which carries a high risk of recurrence and metastasis, face an urgent need for innovative treatment approaches," said Lillian Siu, M.D., director of the Phase I Program at the Princess Margaret Cancer Centre. Alexander Spira, M.D., Ph.D., chief executive officer of NEXT Oncology-Virginia, added, "RGT-61159 has a novel mechanism of action and targets a known oncogenic driver. We are pleased to collaborate with Rgenta in exploring the potential of this new agent."
