A Study of ABT-301 Plus Tislelizumab With Bevacizumab in pMMR/Non-MSI-H Locally Advanced or mCRC

NCT07244705 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: ABT-301-103
• Study Type: interventional
• Target: 66
• Locations: 2 countries
• Sites: 15

Brief Summary

The goal of this clinical trial is to evaluate the safety and tolerability of escalating doses of ABT-301 in combination with fixed doses of tislelizumab 200 mg IV infusion and bevacizumab 7.5 mg/kg IV infusion Q3W, in participants with pMMR/non-MSI-H colorectal cancer (CRC). It will also determine the maximum tolerated dose (MTD) and select the recommended Phase 2 dose (RP2D) of ABT-301. Participants will receive ABT-301 administered once daily (QD ±3 hours) or twice daily (Q12H ±3 hours, at least 9 hours apart) with water in 21-day treatment cycles. Tislelizumab 200 mg IV and bevacizumab 7.5 mg/kg IV Q3W will be given in both parts of the study.

Conditions

Colorectal Cancer (Diagnosis); Colorectal Cancer Metastatic; Colorectal Cancer (CRC); Immunotherapy

Outcome Measures

Primary Outcomes (3)

• Part I - To evaluate the safety and tolerability of escalating doses of ABT-301 in combination with fixed doses of tislelizumab 200 mg IV infusion and bevacizumab 7.5 mg/kg IV infusion Q3W, in participants with pMMR/non-MSI-H CRC.

  Endpoints include: Adverse Event will be graded using the NCI CTCAE V5.0.

  From screening to 90 days after last dose

• Part I - To determine the Maximum tolerated dose (MTD) and select the recommended Phase 2 dose (RP2D) of ABT-301.

  Endpoints include: Incidence of DLTs during the first cycle of treatment.

  From the first dose of ABT-301 to the completion of the first 21-day cycle of ABT-301 treatment in the last cohort.

• Part II - To evaluate the efficacy of two dosages/schemes of ABT-301 in combination with tislelizumab and bevacizumab.

  Endpoint: ORR per Investigator assessment, according to RECIST version 1.1.

  From baseline until progression of disease or death, whichever occurs first. (up to 28 months)

Secondary Outcomes (18)

• Part I - Objective Response Rate (ORR) per Investigator Assessment According to RECIST v1.1

  From baseline until progression of disease or death, whichever occurs first. (up to 28 months)

• Part I - Duration of Response (DOR) per Investigator Assessment According to RECIST v1.1

  From baseline until progression of disease or death, whichever occurs first. (up to 28 months)

• Part I - Progression-Free Survival (PFS) per Investigator Assessment According to RECIST v1.1

  From baseline until progression of disease or death, whichever occurs first. (up to 28 months)

• Part I - Overall Survival (OS)

  From baseline until progression of disease or death, whichever occurs first. (up to 28 months)

• Part I - To characterize the PK of repeated doses of ABT-301 in participants with pMMR/non-MSI-H CRC.

  From Cycle 1 Day 1 through Cycle 2 Day 1 (each cycle is 21 days)

Study Arms (2)

Part 1 (Dose Escalation Phase)

EXPERIMENTAL

Drug: ABT-301; Drug: Tislelizumab; Drug: Bevacizumab (Avastin)

Part 2 (Dose Optimization Phase)

EXPERIMENTAL

Drug: ABT-301; Drug: Tislelizumab; Drug: Bevacizumab (Avastin)

Interventions

ABT-301 DRUG

ABT-301 is an oral histone deacetylase inhibitor (HDACi) administered in capsule form once daily (QD ±3 hours) or every 12 hours (Q12H ±3 hours, with at least 9 hours between doses) with water in 21-day treatment cycles. In Part 1 (dose-escalation phase), participants receive escalating doses of ABT-301 (50 mg QD, 100 mg QD, 50 mg Q12H, 150 mg QD, or 75 mg Q12H). Tislelizumab 200 mg and bevacizumab 7.5 mg/kg will be administered through IV infusion on Day 1 of every 21-day treatment cycle. This phase aims to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of ABT-301 when combined with tislelizumab and bevacizumab. In Part 2 (dose-optimization phase), two ABT-301 doses/schedules will be selected for further evaluation of antitumor activity, safety, and tolerability in adults with pMMR/non-MSI-H colorectal cancer (CRC).

Also known as: MPT0E028, Imofinostat

Part 1 (Dose Escalation Phase); Part 2 (Dose Optimization Phase)

Tislelizumab DRUG

Tislelizumab is a humanized immunoglobulin G4-variant monoclonal antibody (mAb) blocking programmed cell death protein 1 (PD-1). Tislelizumab 200 mg will be administered through IV infusion on Day 1 of every 21-day treatment cycle in combination with ABT-301 and bevacizumab throughout both parts of the study.

Part 1 (Dose Escalation Phase); Part 2 (Dose Optimization Phase)

Bevacizumab (Avastin) DRUG

Bevacizumab (Avastin®) is a recombinant humanized monoclonal IgG1 antibody which binds to and neutralizes VEGF. Neutralization of VEGF by bevacizumab has been shown to inhibit the VEGF-induced proliferation of human endothelial cells in vitro and to decrease micro-vessel density and interstitial pressure in tumor xenografts in vivo. Bevacizumab 7.5 mg/kg will be administered through IV infusion on Day 1 of every 21-day treatment cycle in combination with ABT-301 and tislelizumab, throughout both parts of the study.

Part 1 (Dose Escalation Phase); Part 2 (Dose Optimization Phase)

Eligibility Criteria

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

You may qualify if:

• Participant must be ≥18 years at the time of signing the informed consent.
• Participant with pMMR/non-MSI-H advanced/recurrent histologically confirmed CRC with at least one measurable lesion, per RECIST version 1.1.
• Participant must have received ≥2 lines of prior systemic therapy (including but not limited to chemotherapeutic agents of 5-fluorouracil, oxaliplatin, irinotecan; participant may or may not have received biologic agents such as cetuximab, panitumumab, aflibercept, ramucirumab, bevacizumab; tyrosine kinase inhibitors of regorafenib, fruquintinib).
• NOTE: Participants with BRAF V600E, HER2 amplification/ mutation, KRAS G12C mutation, NTRK gene fusion, RET fusion, may or may not have received relevant targeted therapy and failed.
• Participant must submit an archival formalin-fixed, paraffin-embedded tumor specimen collected within 5 years before screening. If archival specimens are unavailable, alternative samples, such as colon endoscopy biopsy, are acceptable.
• NOTE: For participants who consent to join the exploratory biomarker study, a fresh biopsy sample is required during the screening and treatment periods. Exceptions may be granted if tumor tissue cannot be obtained due to specific circumstances.
• Tumor tissues were identified as pMMR by immunohistochemistry (IHC) method or nonMSI-H by polymerase chain reaction (PCR) (Appendix 13).
• ECOG Performance Status of 0 or 1.
• Adequate hematologic and end-organ function, defined by laboratory data obtained within 7 days prior to the first dose of study intervention:
• Absolute neutrophil count ≥1.5 × 109/L (1500/μL) without granulocyte colony-stimulating factor support.
• Lymphocyte count \>0.5 × 109/L (500/µL).
• Platelet count \>100 × 109/L (100,000/μL), without transfusion.
• Hemoglobin \>90 g/L (9 g/dL), participants may be transfused to meet this criterion.
• AST, ALT, and ALP \<2.5 × ULN (must be ≤5 × ULN for participants with liver metastases).
• Total serum bilirubin \<1.5 × ULN (\<3 × ULN in the presence of documented Gilbert's syndrome \[unconjugated hyperbilirubinemia\] or liver metastases at baseline).

You may not qualify if:

• History of leptomeningeal disease.
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, multiple sclerosis, or ankylosing spondylitis.
• EXCEPTIONS:
• Participants with the following conditions are eligible for the study: autoimmune-related hypothyroidism on thyroid-replacement hormone are eligible for the study. Participants with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Participants with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., participants with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met: 1. Rash must cover \<10% of body surface area 2. Disease is well controlled at baseline and requires only low-potency topical corticosteroids 3. No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
• EXCEPTIONS:
• o History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Active tuberculosis.
• Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within three months prior to initiation of study intervention, unstable arrhythmia, or unstable angina.
• NOTE: Participants are not eligible for the study if they have or are
• A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>450 milliseconds).
• A history of additional risk factors for torsades de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
• Using concomitant medications that prolong the QT/QTc interval. - Major surgical procedure, other than for diagnosis, within four weeks prior to initiation of study intervention, or anticipation of need for a major surgical procedure during the study.
• History of malignancy other than CRC within five years prior to screening.

Sponsors & Collaborators

• Anbogen Therapeutics, Inc.: lead
• Fortrea: collaborator

Study Sites (15)

Liverpool Cancer Therapy Centre

Liverpool, New South Wales, 2170, Australia

NOT YET RECRUITING

Macquarie University Hospital (MUH)

Macquarie Park, New South Wales, 2109, Australia

NOT YET RECRUITING

Scientia Clinical Research

Randwick, New South Wales, 2031, Australia

RECRUITING

Greenslopes Private Hospital - Cyril Gilbert Cancer Centre

Greenslopes, Queensland, 4120, Australia

NOT YET RECRUITING

The Queen Elizabeth Hospital (TQEH)

Woodville South, South Australia, 5011, Australia

NOT YET RECRUITING

Monash University - Faculty of Medicine, Nursing and Health Sciences

Clayton, Victoria, 3800, Australia

NOT YET RECRUITING

Austin Health - Cancer Clinical Trials Centre (CCTC)

Heidelberg, Victoria, 3084, Australia

NOT YET RECRUITING

Linear Clinical Research

Nedlands, Western Australia, 6009, Australia

NOT YET RECRUITING

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

NOT YET RECRUITING

E-Da Cancer Hospital

Kaohsiung City, 824, Taiwan

NOT YET RECRUITING

Chang Gung Medical Foundation, Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 833, Taiwan

NOT YET RECRUITING

Taipei Medical University Shuang Ho Hospital, Ministry of Health and Welfare

New Taipei City, 235, Taiwan

NOT YET RECRUITING

National Cheng Kung University Hospital

Tainan, 701, Taiwan

NOT YET RECRUITING

National Taiwan University Hospital - Cancer Center

Taipei, 100, Taiwan

NOT YET RECRUITING

Chang Gung Medical Foundation, Linkou Chang Gung Memorial Hospital

Taoyuan District, 333, Taiwan

NOT YET RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms; Disease

Interventions

3-(1-benzenesulfonyl-2,3-dihydro-1H-indol-5-yl)-N-hydroxyacrylamide; tislelizumab; Bevacizumab

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; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Ryan Hua

CONTACT

+886-2-8979-8616; abt301-103@anbogen.com

Study Design

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

Study Record Dates

• First Submitted: November 10, 2025
• First Posted: November 24, 2025
• Study Start: November 1, 2025
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: November 24, 2025

Record last verified: 2025-11

Locations

TW (7); AU (8)