RC48-ADC Combined With Bevacizumab in HER2-positive Advanced Colorectal Cancer

RC48-ADC Combined With Bevacizumab in HER2-positive Advanced Colorectal Cancer：a Single-arm, Non-randomized, Single-center Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: RC48-ADC plus Bevacizumab

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 Medication must be discontinued until disease progression, intolerable toxicity, informed consent is withdrawn, or investigator judgment is made.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).

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Caixia Dong; Phone Number: +86 15068882349; Email: dcx_1982@163.com
• Study Contact Backup: Name: Ying Yuan; Phone Number: +86 13858193601; Email: yuanying1999@zju.edu.cn

Study Locations

• China
  • Zhejinag
    • Hangzhou, Zhejinag, China, 310009
      • Recruiting
      • The Second Affiliated Hospital of Zhejiang University
      • Contact: Yuan Ying, ph.D & MD; Email: yuanying1999@zju.edu.cn
      • Contact: YUAN YING; Email: yuanying1999@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RC48-ADC plus Bevacizumab; 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.	Drug: RC48-ADC plus Bevacizumab; Administer RC48-ADC intravenously in combination with bevacizumab 5mg/kg once every two weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Objective Response Rate was defined as the proportion of patients with a best objective response of complete response (CR) or partial response (PR) according to RECIST criteria (version 1.1)	From Baseline to disease progress, up to 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Progression-free survival is defined as the time from enrollment to the first documented disease progression according to RECIST version 1.1, or to death from any cause, whichever occurred first	From Baseline to primary completion date, about 2 years
Overal survival	Time from randomization to death (from any cause)	From Baseline to primary completion date, about 5 years

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Study Chair: Ying Yuan, The Second Affiliated Hospital of Medical College of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2023
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: March 13, 2023
• First Submitted That Met QC Criteria: March 24, 2023
• First Posted (Actual): March 27, 2023

Study Record Updates

• Last Update Posted (Actual): October 31, 2023
• Last Update Submitted That Met QC Criteria: October 30, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Colorectal Cancer; Her2-positive; RC48-ADC
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: 2023-010

Drug and device information, study documents

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