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

Official title

A Phase 1a/1b, First-in-human, Multicenter Study to Assess the Efficacy and Safety of RGT-61159 for Treatment of Patients With Relapsed/Refractory Adenoid Cystic Carcinoma (ACC) or Colorectal Carcinoma (CRC)

Overview

Phase 1 study to evaluate safety, tolerability and anti-tumor activity of RGT-61159 in patients with ACC or CRC

Detailed description

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.

Interventions

• Drug RGT-61159
  Oral MYB inhibitor

Primary outcome measures

• Number and type of dose-limiting toxicities (DLTs) in first cycle of administration [Time frame: 21 days]
• Number and type of adverse events [Time frame: Through study completion, estimated as 30 days after last dose of study drug]
• Recommended Phase 2 Dose (RP2D) [Time frame: Assessed at the end of Cycle 1 for each subject (each cycle 21 days)]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 8 centers

• Dana-Farber Cancer Institute — Boston
• University of Michigan — Ann Arbor
• Washington University School of Medicine — St Louis
• Laura & Isaac Perlmutter Cancer Center at NYU Langone Health — New York
• Memorial Sloan Kettering Cancer Center — New York
• MD Anderson Cancer Center — Houston
• Next Oncology VA — Fairfax
• Fred Hutchinson Cancer Center — Seattle

Canada · 2 centers

• Ottawa Hospital Cancer Centre — Ottawa
• Princess Margaret Cancer Center — Toronto

Identifiers

NCT: NCT06462183 · RGT61159-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗