Safety and Efficacy of Tegavivint in Patients With Metastatic Colorectal Carcinoma

NCT07463599 | Recruiting Phase 1 FDA Drug

• 1 other identifier: ITER-003-CRC
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 1

Brief Summary

This trial will evaluate the safety, tolerability, and preliminary efficacy of tegavivint as monotherapy (single) and in combination with standard therapies in patients with metastatic colorectal carcinoma (mCRC).

Conditions

Metastatic Colorectal Carcinoma (mCRC); Colorectal Cancer (CRC); Adenomatous Polyposis Coli (APC) Gene Mutation; Catenin Beta-1 (CTNNB1) Gene Mutation

Outcome Measures

Primary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  To establish the safety of tegavivint monotherapy treatment related toxicities as per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTC AE V5.0)

  ~24 months

• Maximum Tolerated Dose (MTD)/Administered Dose

  To determine the MTD and/or Recommended Phase 2 dose (RP2D) of tegavivint monotherapy. The dose escalation/de-escalation decisions will be made based on isotonic regression of dose-limiting toxicity (DLT) rates across all dose levels. The MTD will be selected as the dose with an estimated DLT probability closest to the target of 30% among the doses tested.

  ~24 months

Secondary Outcomes (6)

• Response Rates

  ~24 months

• Maximum Observed Concentration (Cmax) of Tegavivint [Pharmacokinetics (PK)]

  ~24 months

• Time to Maximum Observed Concentration (Tmax) of Tegavivint [Pharmacokinetics (PK)]

  ~24 months

• Elimination Half-Life (t1/2) of Tegavivint [Pharmacokinetics (PK)]

  ~24 months

• Total Body Clearance (CL) of Tegavivint [Pharmacokinetics (PK)]

  ~24 months

Other Outcomes (4)

• Expression Level of β-catenin [Pharmacodynamics (PD)]

  ~36 months

• Levels of Circulating Tumor DNA (ctDNA) [Pharmacodynamics (PD)]

  ~36 months

• Expression Levels of Wnt-Responsive Proteins in Serum [Pharmacodynamics (PD)]

  ~36 months

Study Arms (6)

Part 1 - Tegavivint Monotherapy Dose Escalation

EXPERIMENTAL

Limited tegavivint monotherapy dose escalation using a Bayesian optimal interval (BOIN) design, starting at 6.5 mg/kg intravenously (IV) (weekly on day 1, 8, 15, and 22 of a 28-day cycle) to determine the MTD and/or RP2D. Dosing may be de-escalated to 5 mg/kg or escalated to 8 or 10 mg/kg dependent on isotonic regression of DLT rates across all dose levels.

Drug: Tegavivint

Part 2 - Tegavivint Monotherapy Phase 2 Dose Expansion

EXPERIMENTAL

Expansion cohort receiving tegavivint monotherapy at RP2D determined in Part 1 dose escalation to assess the safety profile and preliminary efficacy of tegavivint monotherapy using the Bayesian Optimal Phase 2 (BOP2) design.

Drug: Tegavivint

Part 3 - Arm A: Combination Dose Escalation of Tegavivint + Standard of Care Treatment

EXPERIMENTAL

Drug: Tegavivint

Part 4 - Arm A: Tegavivint + Stand of Care Expansion

EXPERIMENTAL

Drug: Tegavivint

Part 3 - Arm B: Tegavivint + Stand of Care Escalation

EXPERIMENTAL

Drug: Tegavivint

Part 4 - Arm B: Tegavivint + Standard of Care Dose Expansion

EXPERIMENTAL

Drug: Tegavivint

Interventions

Tegavivint DRUG

Tegavivint is a first-in-class chemical inhibitor that interferes with the binding of Transducin beta-like protein 1 (TBL1) to beta-catenin.

Also known as: BC2059

Part 1 - Tegavivint Monotherapy Dose Escalation; Part 2 - Tegavivint Monotherapy Phase 2 Dose Expansion; Part 3 - Arm A: Combination Dose Escalation of Tegavivint + Standard of Care Treatment; Part 3 - Arm B: Tegavivint + Stand of Care Escalation; Part 4 - Arm A: Tegavivint + Stand of Care Expansion; Part 4 - Arm B: Tegavivint + Standard of Care Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form (ICF)
• Male or female, 18 years of age or older
• Histologically and/or cytologically documented metastatic colorectal adenocarcinoma (all other histological types are excluded)
• a. RAS, BRAF, and MSI/ dMMR (Mismatch repair deficiency) status for each patient must be documented.
• Disease progression or intolerance to ≥ 2 lines of systemic therapy for advanced/metastatic disease, including the following prior therapies unless contraindicated: fluoropyrimidine-, oxaliplatin- and irinotecan-based regimens, an anti-vascular endothelial growth factor (VEGF) therapy, and if RAS wild-type, an anti-epidermal growth factor receptor (EGFR) therapy.
• Prior treatment with trifluridine-tipiracil or fruquintinib is allowed
• Patients with BRAF-mutant tumors must have been treated with a BRAF inhibitor
• Patients with microsatellite-high or mismatch repair deficient tumors must have been treated with immune checkpoint inhibitors
• Measurable disease as defined by RECIST 1.1. Lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, may be considered measurable if progression has been demonstrated in such lesions.
• Willingness and ability to provide tumor biopsies during screening and while on treatment. On trial, biopsies considered low risk are required, moderate risk procedures are optional, and no high-risk procedures are allowed.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 prior to the first dose of the investigational product(s)
• Patients must have organ and marrow function as defined below during screening and performed by local laboratories within 7 days of the first dose of the investigational product(s):
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
• Platelets ≥ 100 × 109/L; no transfusion within 7 days prior to the screening laboratory assessment
• Hemoglobin ≥ 9 g/dL

You may not qualify if:

• Patients receiving therapy with other anti-neoplastic or experimental agents.
• Patients receiving concomitant strong or moderate inhibitors of CYP3A4/5 that cannot be discontinued 7 days or 5 half-lives (whichever is longer) prior to Cycle 1 Day 1.
• Patients receiving concomitant strong or moderate inducers of CYP3A4/5 that cannot be discontinued at least 14 days prior to Cycle 1 Day 1.
• Patients with known history of Gilbert's syndrome or other genetic conditions affecting UGT1A1 function.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to tegavivint, or other agents and excipients used in the trial including allergic reactions to Food, Drug, and Cosmetic (FD\&C) Yellow No. 5 (Tartrazine) or No. 6 (Sunset Yellow FCF).
• Malignant disease, other than that being treated in this trial. Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) who have undergone potentially curative therapy are not excluded. Other exceptions include malignancies that were treated curatively and have not recurred within 3 years prior to Cycle 1 Day 1 and any malignancy considered indolent and that has never required therapy.
• Lack of peripheral venous or central venous access or any condition that would interfere with drug administration or collection of trial samples.
• Inability to swallow capsules or tablets.
• Known central nervous system (CNS) involvement including carcinomatous meningitis.
• Patients with large varices at risk of significant bleeding that are not being treated with conventional medical intervention: beta blockers or endoscopic treatment. Assessment of varices for patients in whom conventional medical intervention for known varices is already in place should be performed by endoscopy as per local standard of care.
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within 6 months before the start of trial medication.
• Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, or hypertension including any of the following:
• Congestive heart failure, New York Heart Association (NYHA) \> Class II
• Uncontrolled hypertension (systolic blood pressure \>150 mmHg or diastolic pressure \> 90 mmHg despite optimal medical management)
• Unstable angina pectoris or cardiac arrhythmia

Sponsors & Collaborators

• HonorHealth Research Institute: lead
• Iterion Therapeutics: collaborator

Study Sites (1)

Clinical Trials Nurse Navigator

Scottsdale, Arizona, 85258, United States

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms; Adenomatous Polyposis Coli

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Adenomatous Polyps; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplastic Syndromes, Hereditary; Intestinal Polyposis; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2026
• First Posted: March 11, 2026
• Study Start: February 17, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): July 1, 2029
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)