The Phase 1b/IIa, Open-label, Dose Escalation and Dose Expansion to Evaluate Safety, Tolerability, and Preliminary Efficacy of the Combination of HCB101, Cetuximab/Bevacizumab, and FOLFOX/FOLFIRI in Advanced or Metastatic Colorectal Cancer

NCT07204574 | Recruiting Phase 1 DMC

• 1 other identifier: 202401753A0
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a non-randomized, open-label, dose-escalation and dose-expansion phase I/II clinical study to evaluate the safety, tolerability, and efficacy of HCB101 in combination with Cetuximab/Bevacizumab, and FOLFOX/FOLFIRI in Advanced or Metastatic Colorectal Cancer. The trial consists of two phases: the dose-escalation phase (I) and the dose-expansion phase (II). Subjects will receive a weekly single dose of HCB101 IV infusion over 60 (±10) minutes on Days 1, 8, and 15 in each 21-day cycle in combination with Bevacizumab (5 mg/kg IV day 1; given every 14 days) /Cetuximab (500 mg/m2 IV day 1; given every 14 days) , and FOLFIRI/FOLFOX until unacceptable AE(s), radiographic or clinically documented disease progression, withdrawal of consent, loss to follow-up, death, or termination of the study whichever occurs first.

Conditions

CRC

Outcome Measures

Primary Outcomes (2)

• Number of subjects with MTD of HCB101 in combination with Cetuximab/Bevacizumab, and FOLFOX/FOLFIRI

  To evaluate the safety and efficacy of HCB101 in combination with Cetuximab/Bevacizumab, and FOLFOX/FOLFIRI

  2 Years

• Overall Rate Response (ORR)

  To evaluate the safety and efficacy of HCB101 in combination with Cetuximab/Bevacizumab, and FOLFOX/FOLFIRI

  2 Years

Secondary Outcomes (2)

• Number/incidence and percentage of subjects with AEs, SAEs, and TEAEs

  2 Years

• Progression-Free Survival (PFS)

  2 Years

Study Arms (1)

Experimental: HCB101+ Bevacizumab/Cetuximab+ Cetuximab/FOLFOX

EXPERIMENTAL

Drug: HCB101; Drug: Bevacizumab; Drug: Cetuximab (Erbitux); Drug: FOLFIRI (Fluorouracil (5-FU), leucovorin, irinotecan); Drug: FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil)

Interventions

HCB101 DRUG

QW

Experimental: HCB101+ Bevacizumab/Cetuximab+ Cetuximab/FOLFOX

Bevacizumab DRUG

5 mg/kg IV infusion, Day 1, Every 2 weeks

Experimental: HCB101+ Bevacizumab/Cetuximab+ Cetuximab/FOLFOX

Cetuximab (Erbitux) DRUG

* Initial dose: 400 mg/m² IV infusion, over \>2 hours, Day 1 * Maintenance dose: 250 mg/m² IV infusion, over 60 minutes, Day 1, weekly OR 500 mg/m² IV infusion, over \>2 hours, Day 1, every 2 weeks

Experimental: HCB101+ Bevacizumab/Cetuximab+ Cetuximab/FOLFOX

FOLFIRI (Fluorouracil (5-FU), leucovorin, irinotecan) DRUG

Irinotecan: 180 mg/m² IV infusion over 30-90 minutes, Day 1, Every 2 weeks Folinic acid (Leucovorin): 400 mg/m² IV infusion over 2 hours, Day 1, Every 2 weeks 5-Fluorouracil (5-FU): 400 mg/m² IV bolus, Day 1; then 1200 mg/(m²·day) × 2 days continuous IV infusion (total 2400 mg/m² over 46-48 hours, Every 2 weeks

Experimental: HCB101+ Bevacizumab/Cetuximab+ Cetuximab/FOLFOX

FOLFOX (Oxaliplatin/Leucovorin/5-Fluorouracil) DRUG

Folinic acid (Leucovorin): 400 mg/m² IV infusion over 2 hours, Day 1, Every 2 weeks 5-Fluorouracil (5-FU): 400 mg/m² IV bolus, Day 1; then 1200 mg/(m²·day) × 2 days continuous IV infusion (total 2400 mg/m² over 46-48 hours), Every 2 weeks Oxaliplatin: 85 mg/m² IV infusion over 2 hours, Day 1, Every 2 weeks

Experimental: HCB101+ Bevacizumab/Cetuximab+ Cetuximab/FOLFOX

Eligibility Criteria

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

You may qualify if:

• Subjects are able to understand and willing to provide signed informed consent as described in Appendix 1, Section 10.1.3, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol, including study visits and study-related procedures.
• Male and female subjects of ≥18 years of age, inclusive, at the time of signing the informed consent.
• With histologically/cytologically confirmed diagnosis of unresectable locally advanced or metastatic colorectal cancer, with both RAS and BRAF wild-type, who have experienced treatment failure with prior chemotherapy for locally advanced or metastatic disease (intended for second-line treatment). Previous chemotherapy may have included 5-FU, oxaliplatin, or irinotecan.
• Must have at least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 at Screening.
• Able to provide archived or fresh tumor tissue samples for CD47 expression, immune score, and whole-exome sequencing (WES) analysis, if applicable.
• Have a life expectancy of ≥12 weeks (according to the Investigator's judgment).
• Have adequate organ function, as indicated by the following laboratory parameters in below (had not received a blood transfusion, apheresis infusion, erythropoietin, granulocyte colony-stimulating factor, and other relevant medical support within 14 days prior to the administration of the first dose of study intervention).
• \-- a) Absolute neutrophil count ≥1.5 × 109/L
• \-- b) Platelets ≥75 × 109/L
• \-- c) Hemoglobin ≥9.5 g/dL
• d) Total bilirubin ≤1.5 × upper limit of normal (ULN), \<3.0 × ULN if known Gilbert's disease
• e) Alanine aminotransferase and aspartate aminotransferase ≤3× ULN and ≤5× ULN for subject with liver metastasis
• f) Creatinine clearance ≥30 mL/min (using Cockcroft Gault equation)
• g) Coagulation: International normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (aPTT) ≤1.5× ULN (The INR applies only to subjects who do not receive therapeutic anticoagulation).

You may not qualify if:

• Subjects are excluded from the study if any of the following criteria apply:
• Medical Conditions
• With a known history of hypersensitivity to any components of the study intervention.
• With other malignancies requiring treatment within 2 years prior to the first dose will be excluded, except for locally curable basal cell or squamous cell skin cancer treated with curative intent, and other malignancies with no recurrence within 2 years.
• Primary tumor in the central nervous system (CNS), or active or untreated CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate, provided they are clinically stable for at least 28 days and have no evidence of new or enlarging brain metastases and no requirements for high-dose corticosteroids 14 days prior to dosing with study intervention. Subjects on low-dose corticosteroids (\<20 mg prednisone or equivalent per day) may participate.
• Clinically significant cardiovascular condition, including:
• History of congestive heart failure (New York Heart Association Class \>2);
• History of unstable angina within 6 months prior to the first dose of study intervention;
• New-onset angina or myocardial infarction within 6 months prior to the first dose of study intervention;
• New-onset of atrial fibrillation, supraventricular arrhythmia, or ventricular arrhythmia within 6 months prior to the first dose of study intervention and still in unstable condition and requiring treatment or intervention. History of atrial fibrillation, supraventricular arrhythmia, or ventricular arrhythmia will be allowed, provided the condition is stably controlled.
• History or presence of an abnormal ECG that, in the Investigator's opinion, is clinically meaningful (including QT interval corrected for heart rate using Fridericia's correction \[QTcF\] \>470 msec at Screening, pacemaker installation, or previous diagnosis of congenital long QT syndrome).
• Any previous treatment-related toxicities which have not recovered to ≤ Grade 1 as evaluated by National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 or baseline, except alopecia and anemia (Note: subjects with chronic Grade 2 toxicities which are well managed and stable may be eligible per the discretion of the Investigator after discussion with the Sponsor and medical monitor, e.g., Grade 2 chemotherapy-induced neuropathy.)
• \. With known inherited or acquired bleeding disorders or bleeding diathesis. 7. Known congenital or acquired bleeding disorders or bleeding tendency. 8. Have RBC transfusion dependence defined as requiring more than 2 units of RBC transfusions during the 4-week period prior to Screening.
• \. With a previously documented diagnosis of hemolytic anemia or Evans Syndrome in the last 3 months.
• Prior/Concomitant Therapy/Treatment 10. Subjects who have undergone major surgery, or have undergone radical radiotherapy within 28 days prior to the first dose of study intervention.

Sponsors & Collaborators

• Chang Gung Memorial Hospital: lead
• FBD Biologics Limited: collaborator

Study Sites (1)

Linkou Chang-Gung Memorial Hospital

Taoyuan District, Taiwan

RECRUITING

MeSH Terms

Interventions

Bevacizumab; Cetuximab; Fluorouracil; Leucovorin; Irinotecan; Folfox protocol; Oxaliplatin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Camptothecin; Alkaloids; Coordination Complexes; Organic Chemicals

Study Officials

• Hung-Chih Hsu

  Chang Gung Memorial Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hung-Chih Hsu

CONTACT

+886-975-368-118; dannyhsuyoyo@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending Physician

Study Record Dates

• First Submitted: September 24, 2025
• First Posted: October 2, 2025
• Study Start: May 14, 2025
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: October 2, 2025

Record last verified: 2025-09

Locations

TW (1)