Clinical trial NCT05785325: RC48-ADC Combined With Bevacizumab in HER2-positive Advanced Colorectal Cancer
Official title: RC48-ADC Combined With Bevacizumab in HER2-positive Advanced Colorectal Cancer：a Single-arm, Non-randomized, Single-center Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: RC48-ADC
Her2-positive
Colorectal Cancer
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
First posted: 2023-03-27
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A phase II clinical study of RC48-ADC combined with Bevacizumab as late-line treatment in patients with HER2-expressed metastatic colorectal cancer. A total of 30 patients are planned to be enrolled.

Detailed description: This is a single-arm, non-randomized, single-center trial. Enroll 30 patients with HER2-expressed metastatic colorectal cancer and failure of standard therapy. Divide into 2 cohorts, including 10 patients with low HER2 expression (IHC 2+/FISH negative) and 20 patients with high HER2 expression (IHC 2+/FISH positive or IHC3+). Administer RC48-ADC intravenously in combination with bevacizumab 5mg/kg once every two weeks. Medication must be discontinued until disease progression, intolerable toxicity, informed consent is withdrawn, or investigator judgment is made. The primary endpoints is objective response rate (ORR), and secondary endpoints are progression-free survival (PFS), overall survival (OS), and adverse effects (AE).

Eligibility criteria: Inclusion Criteria:

1. Age 18 or above, male or female;
2. Advanced inoperable colorectal cancer confirmed by pathology;
3. At least 1 measurable lesion meeting RECIST v1.1 criteria;
4. Patients who had received at least oxaliplatin, irinotecan, and fluorouracil for advanced or metastatic disease progressed or were intolerant were admitted to the study; Patients who had previously received anti-HER2 therapy such as trastuzumab and lapatinib were allowed to be included;
5. ECOG PS: 0-2 points;
6. Patients with HER2 expression: IHC results 2+ or 3+.
7. Predicted survival ≥12 weeks;
8. Women of childbearing age must already be using reliable contraception or have had a pregnancy test (serum or urine) with negative results within 7 days prior to inclusion and be willing to use an appropriate method of contraception during the trial period and 8 weeks after the last test drug administration. For males, consent is required to use an appropriate method of contraception or surgical sterilization during the trial period and 8 weeks after the last administration of the trial drug;
9. The subjects voluntarily joined the study and signed the informed consent. The subjects had good compliance and cooperated with follow-up visits.

Exclusion Criteria:

1. Known allergy to MMAE conjugate of recombinant humanized anti-HER2 monoclonal antibody for injection;
2. Clinical symptoms or diseases of the heart that are not well controlled, such as heart failure of grade 2 or above; b. Unstable angina pectoris; c. Myocardial infarction within 1 year; d. Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention;
3. There are contraindications for the use of bevacizumab such as severe active bleeding, severe arteriovenous thrombosis events, gastrointestinal obstruction and perforation, and uncontrolled hypertension
4. Major surgical treatment, open biopsy, or significant traumatic injury was received within 28 years prior to treatment
5. In the investigator's judgment, subjects had other factors that might have led to the termination of the study, such as other serious medical conditions (including mental illness) requiring concomitant treatment, serious laboratory abnormalities, and family or social factors that might have affected subjects' safety or the collection of data and samples.

Primary outcomes:
measure: Objective Response Rate
timeFrame: From Baseline to disease progress, up to 18 months
Secondary outcomes:
measure: Progression free survival
timeFrame: From Baseline to primary completion date, about 2 years
measure: Overal survival
timeFrame: From Baseline to primary completion date, about 5 years
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The second affiliated hospital of Zhejiang University
state: Zhejinag
Study officials:
affiliation: The Second Affiliated Hospital of Medical College of Zhejiang University
name: Ying Yuan
role: STUDY_CHAIR
References: