Evaluate Preliminary Anti-tumor Activity of Elraglusib in Adult Participants With Advanced Solid Tumors

Phase 1/2 Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-Tumor Activity of Elraglusib Oral Tablets in Adult Participants With Advanced Solid Tumors.

This study is being done to test the safety of elraglusib when taken once a day and to assess:

• How the body processes the drug (pharmacokinetics)
• Assess potential effects of the drug on heart rhythm
• Find the highest daily dose that can be given without causing side effects

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Malignant Solid Tumor
• Intervention / Treatment: Drug: Elraglusib Oral Tablets

Detailed Description

The study is a Phase 1/2, open label, dose escalation, safety, PK, PD and antitumor activity study of elraglusib tablets in participants aged 18 years or older with a histologically or cytologically confirmed diagnosis of advanced metastatic or progressive malignant solid tumors who are intolerant of or the malignancy is refractory to established therapy know to provide clinical benefit for their condition, or the malignancy has relapsed after standard therapy. Participants must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 measured by computed tomography (CT) scan or MRI to be eligible.

The study's primary objective is to determine the MTD or MAD and DLTs of elraglusib tablets administered daily. The secondary objectives are to study the PK of elraglusib tablets, to evaluate preliminary antitumor activity of elraglusib when administered as tablets, and to establish the RDEs of elraglusib tablets in subsequent development.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must meet all of the following criteria to be eligible for inclusion in the study:

  1. Able to understand and voluntarily sign a written informed consent and is willing and able to comply with the protocol requirements including scheduled visits, treatment plan, laboratory tests and other study procedures
  2. Age ≥ 18 years

  3. Has histologically or cytologically confirmed diagnosis of advanced metastatic or progressive solid tumor characterized by one or more of the following:

     1. Participant is intolerant of existing therapy(ies) known to provide clinical benefit for their condition
     2. Malignancy is refractory to existing therapy(ies) known to potentially provide clinical benefit
     3. Malignancy has relapsed after standard therapy
     4. Participant has contraindication to or declines standard therapies
  4. Has at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, measured preferably by computed tomography (CT) scan or magnetic resonance image (MRI)

  5. Has laboratory function within specified parameters (may be repeated):

     1. Adequate bone marrow function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L; hemoglobin ≥ 8.5 g/dL, platelets ≥ 100 x 103/μL
     2. Adequate liver function: transaminases (aspartate aminotransferase/ alanine aminotransferase, AST/ALT) and alkaline phosphatase ≤ 2.5 x upper limit of normal (ULN) or ≤ 5 x the ULN if liver metastases are present; total bilirubin ≤ 1.5 x ULN or ≤ 3.0 x ULN if elevations are due to underlying disease or concomitant medication/diseases
     3. Adequate renal function: BSA-adjusted glomerular filtration rate (GFR) ≥ 60 mL/min determined by multiplying estimated GFR by participant's body surface area (BSA) and dividing by 1.73
  6. Eastern Co-operative Oncology Group (ECOG) Performance Status (PS) ≤ 2
  7. Women of childbearing potential must have a negative baseline blood or urine pregnancy test within 72 hours of first dose of study drug. Women may be neither breastfeeding nor intending to become pregnant during study participation and must agree to use effective contraceptive methods (hormonal or barrier method of birth control, or true abstinence) for the duration of study participation and in the following 6 months after discontinuation of study treatment
  8. Male participants with partners of childbearing potential must take appropriate precautions to avoid fathering a child from screening until 6 months after discontinuation of study treatment and use appropriate barrier contraception or true abstinence
  9. Must not be receiving any other investigational medicinal product

Exclusion Criteria:

• Participants who meet any of the following criteria will be excluded from the study:

  1. Pregnant or lactating
  2. Known to be hypersensitive to any of the components of elraglusib tablets or to the excipients used in its formulation
  3. Has not recovered from clinically significant toxicities as a result of prior anticancer therapy, except alopecia and/or infertility. Recovery is defined as ≤ Grade 2 severity per Common Terminology Criteria for Adverse Events (CTCAE), v6.0

  4. The following risk factors for abnormal heart rhythms/QT prolongation:

     1. A history of Torsade de pointes (TdP), other ventricular arrhythmias, or long QT syndrome
     2. A QT or QT interval corrected using Fridericia's formula (QTcF) > 470 msec at Screening from triplicate ECGs
  5. Has significant cardiovascular impairment: congestive heart failure greater than New York Heart Association (NYHA) Class II, family history of long QT syndrome, unstable angina, or stroke within 6 months of the first dose of study therapy
  6. Has had a myocardial infarction within 6 months of the first dose of study therapy or has ECG abnormalities that are deemed medically relevant by the investigator
  7. Has symptomatic brain metastases or leptomeningeal involvement as assessed by CT scan or MRI. Participants with stable brain metastases or leptomeningeal disease are eligible provided they have not required new treatments for this disease in a 28-day period before the first dose of study drug, and anticonvulsants and steroids are at a stable dose for a period of 14 days prior to the first dose of study drug
  8. Has had major surgery within 14 days prior to study entry or is planned to have major surgery during the course of the study (major surgery may be defined as any invasive operative procedure in which an extensive resection is performed, e.g., a body cavity is entered, organs are removed, or normal anatomy is altered. In general, if a mesenchymal barrier is opened [pleural cavity, peritoneum, meninges], the surgery is considered major)
  9. Has any medical and/or social condition which, in the opinion of the Investigator or Medical Monitor would preclude study participation

  10. Previous anticancer therapies with any of the following:

      1. Small molecule ≤ 14 days or 5× the terminal phase elimination t1/2, whichever is shorter, prior to the first dose of study drug
      2. Cytotoxic chemotherapy ≤ 14 days prior to the first dose of study drug
      3. Treatment with biologics (e.g., monoclonal antibodies, bispecific antibodies, cancer vaccines) ≤14 days prior to the first dose of study drug
      4. Broad field radiation therapy ≤14 days prior to the first dose of study drug
      5. Focal radiation therapy (including palliative) ≤ 7 days prior to the first dose of study drug
      6. Systemic and topical corticosteroids ≤ 7 days prior to the first dose of study drug
  11. Use of sensitive substrates of CYP3A4 with a narrow therapeutic from 14 days prior to first administration of study drug, during the study, and until Safety Follow-up Visit.
  12. Use of strong inhibitors or inducers of CYP2C19, CYP1A2 and CYP3A4 from 14 days prior to first administration of study drug, during the study, and until Safety Follow-up Visit.
  13. Use of inhibitors or inducers of major drug transporters (i.e., OATP1B1, OATP1B3, OCT1, OCT2 and MATE1/2K) from 14 days prior to first administration of study drug, during the study, and until the Safety Follow-up Visit.
  14. Concomitant participation in another clinical study with study drug(s) or device
  15. Unable to swallow a tablet or has any condition(s) that, in the opinion of the treating investigator, may affect gastrointestinal absorption
  16. Considered to be a member of a vulnerable population (for example, prisoners)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Elraglusib Monotherapy Dose escalation/de-escalation; Elraglusib 250 mg tablets will be administered once daily with food in 21-day cycles. DG-1: 125mg (Days 1, 3, 5 of a 21 day cycle) DG1: (Starting Dose) 125 mg/QD for 21 days DG2: 250mg/QD for 21 days DG3: 500mg QD for 21 days DG4: 750mg/QD for 21 days, Dosing will continue until MTD or MED is identified. Any higher dose levels which are explored will not exceed 50% increment relative to the prior cohort rounded down to the nearest 250 mg dose (or 125 mg dose if necessary).

Drug: Elraglusib Oral Tablets; Elraglusib Oral Tablet, 250 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and dose-limiting toxicities (DLTs) of elraglusib tablets	Dose escalation/de-escalation decisions and the MTD will be determined at the end of Cycle 1 (each cycle is 21/28days).	Determined at the end of Cycle 1 (each cycle is 21/28days) for each dose group tested up to 24 moths.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Assessment	Characterize Elraglusib Cmax	From date of first dose through completion of Initial 21-day cycle. (Assessed Cycle 1 Only-up to 28 days) for each dose cohort, up to 24 months.
Pharmacokinetic Assessment	Characterize Tmax	From date of first dose through completion of Initial 21-day cycle. (Assessed Cycle 1 Only-up to 28 days) for each dose cohort, up to 24 months.
Pharmacokinetic Assessment	Assessment of half-life (t1/2), area under the plasma concentration-time curve from time 0 to time t (AUC0→t).	From date of first dose through completion of initial 21-day cycle. (Assessed Cycle 1 Only-up to 28 days) for each cohort, up to 24 months.
Pharmacodynamic Assessment	Assess peripheral blood mononuclear cells (PBMCs, both cryopreserved and flash frozen).	From Day 1 Dosing through completion of Day 21 of Cycle 1 only. (Assessed Cycle 1 only, up to 28-days) for each dose cohort up to 24 months.
Pharmacodynamic Assessment	Plasma will be collected to analyze cfDNA.	From date of first dose through completion of Initial 21-day cycle. (Assessed Cycle 1 Only-up to 28 days) for each dose cohort, up to 24 months.
Pharmacodynamic Assessment	Plasma will be collected to analyze cytokines/chemokines.	From date of first dose through completion of Initial 21-day cycle. (Assessed Cycle 1 Only-up to 28 days) for each dose cohort, up to 24 months.
Tumor Assessments	Tumor response based on assessment of target and non-target lesions according to response evaluation criteria in solid tumors (RECIST) criteria.	Baseline and per standard of care every 9 (±1) weeks during treatment and during follow-up through disease progression for unto 30 months.
Electrocardiogram (ECG)	Electrocardiograms will be collected to assess cardiac repolarization (QT) interval.	Participation will be from Date of Screening through completion of the End of Treatment Visit, (EoT Visit), for up to 30 months. (Phase 1 Only)
Electrocardiogram (ECG)	Assessment of cardiac repolarization (QTc) interval.	Participation will be from Date of Screening through completion of the End of Treatment Visit, (EoT Visit), for up to 30 months. (Phase 1 Only)
Safety Assessments	Frequencies and severities of adverse events (AEs)/TEAEs, including DLTs, serious adverse events (SAEs), and laboratory abnormalities that occur in Cycle 1 as well as in later treatment cycles will be assessed for all patients.	From date of randomization until 30 days after receiving their last dose of study drug/completion of the End of Treatment Visit for up to 30 months.
Number of participants with clinically significant changes in laboratory parameters, vital signs, and physical examinations.	Blood and urine samples will be collected for analysis of lab parameters. Vital signs, physical examinations and organ-specific parameters will be collected at specified time points	Participants will be tracked from Date of first dose through completion of end of study/Treatment visit for up to 30 months.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Endpoint Evaluation	Progression-free survival (PFS) [Phase 1 only]	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first. Patient will be assessed up to 30 months or up to 12 months after patient receives last dose of study drug.
Exploratory	Overall survival (OS) (Phase 1 Only)	From date of randomization until the date of first documented progression, date of death from any cause, whichever came first, assessed up to 12 months after receiving their last dose of study drug.

Collaborators and Investigators

• Sponsor: Actuate Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: June 19, 2026
• First Submitted That Met QC Criteria: July 15, 2026
• First Posted (Actual): July 20, 2026

Study Record Updates

• Last Update Posted (Actual): July 20, 2026
• Last Update Submitted That Met QC Criteria: July 15, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: GSK3beta; Solid Tumor; Phase 1/2; Glycogen Synthase Kinase 3 Beta inhibitor; ATR/Chk1; Elraglusib; Elraglusib Oral tablet
• Other Study ID Numbers: Actuate 2601

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No