FDA Alignment Reached on Phase 3 Design for RGT-61159 in ACC

Rgenta Therapeutics has completed an end-of-phase 2 meeting with the FDA and reached alignment on the design of a phase 3 trial of RGT-61159, an oral small molecule targeting the MYB oncogene, in patients with adenoid cystic carcinoma (ACC).¹ The company plans to begin the phase 3 study in the first quarter of 2027.

The planned trial follows preliminary data from the ongoing phase 1a/b study of RGT-61159 (NCT06462183)² in patients with relapsed or refractory ACC or colorectal cancer (CRC), which were presented at ASCO 2026.¹

"Gaining alignment with the FDA on advancing RGT-61159 directly into a phase 3 trial is a significant milestone for Rgenta and the patients we intend to serve,” said Simon Xi, PhD, co-founder and chief executive officer, Rgenta Therapeutics, in a news release.

Phase 3 Trial Design

The planned phase 3 trial is a double-blind, placebo-controlled study that will enroll approximately 150 patients with biomarker-selected, locally advanced, incurable, recurrent or metastatic ACC.¹ Patients will be randomized 2:2:1 to receive oral RGT-61159 at 84 mg once daily, RGT-61159 at 60 mg once daily, or placebo, and all patients will receive best supportive care.

The primary end point is progression-free survival (PFS). Key secondary end points include overall survival (OS), safety, and tolerability. Trial sites are expected in North America and Europe.

Phase 1a/b Data and Clinical Context

In the multicenter, open-label, dose-escalation and expansion phase 1a/b study, the disease control rate was 84.6% (n = 33/39) among evaluable patients treated at or below the recommended phase 2 dose (RP2D), including 3 patients who achieved a partial response per RECIST criteria. Responses deepened with longer treatment: patients with partial responses remained on study for a mean of 8.2 months, and all ongoing patients across the trial had a mean on-study duration of 7.3 months.

The release characterized RGT-61159 as well tolerated at the RP2Ds, with dose-dependent reductions in MYB mRNA and a half-life that supports once-daily oral dosing. The most common adverse events were fatigue, anemia, diarrhea, and nausea.

"The phase 3 clinical trial of RGT-61159 is expected to be the first study of its kind in ACC, marking an important step toward developing new treatment options for these patients. Early clinical data have demonstrated anti-tumor activity and a tolerable safety profile with once-daily oral dosing,” said Alan L. Ho, MD, chief of the Head and Neck Oncology Service, Memorial Sloan Kettering Cancer Center, in the news release.

RGT-61159 and ACC Background

RGT-61159 is an orally available small molecule designed to modulate splicing of the transcription factor MYB, thereby inhibiting production of oncogenic MYB protein, which may inhibit proliferation or induce cell death in cancer cells that overexpress MYB. Aberrant MYB expression has also been demonstrated in acute myeloid leukemia, T-cell acute lymphoblastic leukemia, CRC, small cell lung cancer, and breast cancer.

ACC is a rare malignancy that is estimated to affect approximately 200,000 people worldwide, including 11,000 in the US, and is the second most common cancer arising in the salivary gland. The disease tends to infiltrate surrounding nerves and metastasize to distant sites, and overactivation of MYB is noted in more than 90% of cases. Surgery and radiation, which are among the treatment options, often fail to control local recurrence and distant metastases. No targeted therapies are available for recurrent or metastatic disease.

The FDA granted orphan drug designation to RGT-61159 for the treatment of ACC in September 2025.³

REFERENCES

1. Rgenta Therapeutics announces successful end-of-phase 2 meeting with FDA and alignment on phase 3 trial design for RGT-61159 in patients with adenoid cystic carcinoma (ACC). News release. Rgenta Therapeutics. October 22, 2026. Accessed October 22, 2026. https://tinyurl.com/ydwpm37d

2. Study of safety and efficacy of RGT-61159 in adults with relapsed/refractory adenoid cystic carcinoma (ACC) or colorectal carcinoma (CRC). ClinicalTrials.gov. Updated September 17, 2026. Accessed October 22, 2026. https://clinicaltrials.gov/study/NCT06462183

3. Rgenta Therapeutics receives orphan drug designation from the U.S. FDA for RGT-61159 for the treatment of adenoid cystic carcinoma (ACC). News release. Rgenta Therapeutics. September 17, 2025. Accessed October 22, 2026. https://tinyurl.com/5fdwh8ww