💬In plain words
What the trial is, and whether it could suit you
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.
Sign in to get the eligibility rules as simple questions to take to your doctor.
📋 Eligibility rules (as published)
Inclusion Criteria:
1. 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.
2. Male and female subjects of ≥18 years of age, inclusive, at the time of signing the informed consent.
3. 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.
4. Must have at least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
5. Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 at Screening.
6. Able to provide archived or fresh tumor tissue samples for CD47 expression, immune score, and whole-exome sequencing (WES) analysis, if applicable.
7. Have a life expectancy of ≥12 weeks (according to the Investigator's judgment).
8. 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).
9. A) Female subjects should meet at least 1 of the following criteria before they can participate in the study:
1. Females who have no childbearing potential (i.e., physiologically incapable of pregnancy), including those who have undergone hysterectomy, bilateral oophorectomy, or bilateral salpingectomy.
2. Postmenopausal (total cessation of menses for ≥ 1 year).
3. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test during the Screening Period (within 7 days prior to the first dose of the study intervention), must not be lactating, and must be willing to practice a highly effective contraceptive method throughout the study (i.e., from study entry up to 6 months after the last dose of the study intervention). A highly effective method of contraception is defined as one that results in a low failure rate, i.e., less than 1% per year when used consistently and correctly. For the definition of WOCBP and highly effective methods of contraception.
B) Male subjects are eligible to participate in the study if they have undergone a vasectomy or agree to use a highly effective method of contraception and refrain from donating sperm from study entry up to 6 months after the last dose of the study intervention.
Exclusion Criteria:
Subjects are excluded from the study if any of the following criteria apply:
-Medical Conditions
1. With a known history of hypersensitivity to any components of the study intervention.
2. 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.
3. 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.
4. 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.
5. 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).
6. 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.)
6\. With known inherited or acquired bleeding diso
HealthTeky