Study of Safety and Efficacy of RGT-61159 in Adults With Relapsed/Refractory Adenoid Cystic Carcinoma (ACC) or Colorectal Carcinoma (CRC)

This first-in-human, Phase 1, multi-center, open-label, non-randomized study, is designed to evaluate safety, tolerability, and anti-tumor activity of once-daily RGT-61159 in patients with advanced R/R ACC or R/R CRC for whom standard therapy with proven clinical benefit does not exist, is no longer effective, or is not appropriate. RGT-61159 is an oral, small molecule MYB inhibitor.

Inclusion criteria

• Histologically confirmed ACC or CRC
• Radiographically measurable disease as assessed per RECIST 1.1, with at least 1 site of disease that is measurable and that has not been previously irradiated; or, if the patient has had previous radiation to the target lesion(s), there must be evidence of progression since the radiation
• Patients with locally relapsed/refractory (R/R) advanced or metastatic ACC not amenable to potentially curative surgery or radiotherapy and progression of disease within 12 months at study entry
• Patients with CRC must have locally R/R advanced or metastatic disease not amenable to potentially curative surgery or radiotherapy; must have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidines-, oxaliplatin-, and irinotecan-based chemotherapies, anti-VEGF agents, and if RAS wild-type, an anti-EGFR therapy.
• Adequate hematologic status, organ function, renal function, liver function and prothrombin time (PT) or INR ≤ 1.5 × ULN and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN
• Resolved acute effects of any prior therapy to baseline

Exclusion criteria

• Major surgery or significant traumatic injury within 28 days prior to Cycle 1 Day 1
• Chemotherapy within 14 days prior to Cycle 1 Day 1
• Use of nitrosoureas or mitomycin C within 6 weeks prior to Cycle 1 Day 1
• Radiation therapy within 21 days prior to Cycle 1 Day 1
• Investigational drug use, targeted therapy, or biologic therapy within 28 days or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1
• Ongoing systemic infection requiring treatment with antibiotic, antiviral, or antifungal treatment
• Active known second malignancy
• Clinically significant cardiac disease
• Infection with human immunodeficiency virus (HIV)-1 or HIV-2 unless it's well-controlled HIV (eg, cluster of differentiation 4 [CD4] > 350/mm3 and undetectable viral load)
• Current active liver disease including hepatitis A (hepatitis A [HepA] virus immunoglobulin M [IgM] positive), hepatitis B (hepatitis B virus [HBV] surface antigen positive), or hepatitis C (hepatitis C virus [HCV] antibody positive, confirmed by HCV RNA)
• Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant small bowel resection that would preclude adequate absorption
• Uncontrolled diabetes
• Treatment with a long-acting hematopoietic growth factor within 14 days before Cycle 1 Day 1 or a short-acting hematopoietic growth factor within 7 days before Cycle 1 Day 1
• Treatment with high-dose chemotherapy and stem-cell rescue (autologous stem cell transplant) or allogeneic stem cell transplant within 90 days before Cycle 1 Day 1
• Patients with central nervous system (CNS) metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroid throughout this indication for at least 4 weeks before starting treatment in this study
• History of solid organ transplantation
• Coronavirus disease 2019 (COVID-19) vaccination within 14 days prior to first dose of study drug
• Prior treatment with a MYB inhibitor