A Study of RC48-ADC in Subjects With Advanced Breast Cancer

A Phase Ib Study to Evaluate the Efficacy, Safety and Pharmacokinetics of RC48-ADC for Injection in Subjects With Advanced Breast Cancer With HER2 Positive or HER2 Low Expression

This study will evaluate the efficacy, safety and pharmacokinetics of RC48-ADC for injection in subjects with advanced breast cancer with HER2 positive or HER2 low expression

Study Overview

• Status: Completed
• Conditions: Advanced Breast Cancer
• Intervention / Treatment: Drug: RC48-ADC 1.5 mg/kg (HER2 Positive); Drug: RC48-ADC 2.0 mg/kg (HER2 Positive); Drug: RC48-ADC 2.5 mg/kg (HER2 Positive); Drug: RC48-ADC 2.0 mg/kg (HER2 Low Expression)

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Harbin, China
    • Affiliated Cancer Hospital of Harbin Medical University
  • Hebei, China
    • The Fourth Hospital of Hebei Medical University
  • Nanjing, China
    • Jiangsu Cancer Hospital
  • Beijing
    • Beijing, Beijing, China, 100021
      • Cancer Hospital Chinese Academy of Medical Sciences
  • Jilin
    • Changchun, Jilin, China
      • The first bethune hospital of jilin unversity
  • Liaoning
    • Shenyang, Liaoning, China
      • Liaoning cancer Hospital & Institute
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Zhejiang Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntary signed informed consent;
2. Female, aged between 18 to 70 years;
3. ECOG performance status score of 0 or 1;
4. Life expectancy greater than 12 weeks；

5. Patients with locally advanced or metastatic breast cancer diagnosed by histology or cytology, and:

   1. Core cohort: standard treatment is ineffective (the disease progresses or has no remission after treatment) or cannot tolerate standard treatment, or HER2 positive who cannot receive standard treatment (immunohistochemistry is 2+ and confirmed by fluorescence in situ hybridization [FISH] Positive, or immunohistochemical 3+) patients;
   2. Explorative cohort:standard treatment is ineffective (the disease progresses or has no remission after treatment) or cannot tolerate standard treatment, or had no optional standard treatment for HER2 immunohistochemistry 2+ with FISH negative or HER2 immunohistochemistry 1+ (FISH negative or untested). Subjects in the explorative cohort can provide HER2 detection of tumor primary or metastatic site specimens;
6. Measurable lesion according to the RECIST 1.1;
7. Adequate organ function:

(1)absolute neutrophil count(ANC) >= 1.5 x 10(9)/L; (2) platelets>=100*10(9)/L; (3)Total serum bilirubin <=1.5*ULN; (4)serum aspartate transaminase (AST）and serum alanine transaminase (ALT) <=2.5*ULN, or AST and ALT<=5*ULN with hepatic metastasis; (5) Serum creatinine clearance rate >= 45 mL/min; (6) INR<=1.5*ULN and APTT<=1.5*ULN; 8.Women of child-bearing potential and men must agree to use adequate contraception (e.g., condoms, implants, injectables, combined oral contraceptives, some intrauterine devices, complete sexual abstinence, or sterilized partner) prior to study entry and during the period of therapy and for 6 months after the last dose of study drug; 9.Left ventricular ejection fraction (LVEF) >= 50%.

Exclusion Criteria:

1. Women who are pregnant (positive blood test before medication) or breastfeeding;
2. Patients received anti-cancer therapy within 4 weeks before study drug treatment;, including chemotherapy, radiotherapy, surgery or hormone therapy, molecular targeted therapy (including trastuzumab etc.); Using Trastuzumab emtansine(T-DM1) or participating in the clinical trial on ADC drugs targeting HER2 and bispecific antibodies targeting HER2;
3. The patient have third interstitial fluid (a large number of pleural effusion or ascites) which has clinical symptom or can not be controlled by drainage or other methods;
4. Received Palliative radiation therapy for bone metastases within 2 weeks before study drug treatment;
5. Toxicity of previous anti-tumor treatment has not recovered to CTCAE [version 4.0] 0-1, except for hair loss;
6. Participated in other clinical trials within 4 weeks;
7. Known hypersensitivity or delayed hypersensitivity to the some components of RC48-ADC or similar drugs;
8. The active infection with clinical significance according to the researcher's judgment;
9. Diagnosed with HBsAg or HBcAb positive and HBV DNA positive, or HCV Ab positive, or HIV Ab positive.
10. Have a history of immunodeficiency, including a positive HIV test, or other acquired, congenital immunity Epidemic defects, or a history of organ transplantation;
11. Uncontrolled systemic diseases such as diabetes, hypertension, Pulmonary fibrosis, acute lung disease, interstitial lung disease, etc.
12. Congestive heart failure with grade 2 or higher (including grade 2) of the New York Institute of Cardiology (NYHA) of the United States in the history of diseases such as acute myocardial infarction, unstable angina, stroke, or transient ischemic attack within 6 months prior to entry ;
13. Insufficient adherence to participate in this clinical study;
14. Patients who had received systemic steroid therapy for a long time(Patients who had received systemic steroid therapy for short time and stopped drug more than 2 weeks could be enrolled );
15. Primary brain or metastatic tumor;
16. Peripheral neuropathy with grade≥2;
17. People with a history of mental illness that is difficult to control.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RC48-ADC 1.5 mg/kg (HER2 Positive)	Drug: RC48-ADC 1.5 mg/kg (HER2 Positive); 15 advanced breast cancer participants with HER2 Positive will be treated with RC48-ADC at a dose of 1.5 mg/kg, every 2 weeks. They will continue the medication until one of the following conditions occurred: disease progression, intolerance of toxicity, withdrawal of informed consent, or treatment for 1 year.
Experimental: RC48-ADC 2.0 mg/kg (HER2 Positive)	Drug: RC48-ADC 2.0 mg/kg (HER2 Positive); 15 advanced breast cancer participants with HER2 Positive will be treated with RC48-ADC at a dose of 2.0mg/kg, every 2 weeks. They will continue the medication until one of the following conditions occurred: disease progression, intolerance of toxicity, withdrawal of informed consent, or treatment for 1 year.
Experimental: RC48-ADC 2.5 mg/kg (HER2 Positive)	Drug: RC48-ADC 2.5 mg/kg (HER2 Positive); 15 advanced breast cancer participants with HER2 Positive will be treated with RC48-ADC at a dose of 2.5 mg/kg, every 2 weeks. They will continue the medication until one of the following conditions occurred: disease progression, intolerance of toxicity, withdrawal of informed consent, or treatment for 1 year.
Experimental: RC48-ADC 2.0 mg/kg (HER2 Low Expression)	Drug: RC48-ADC 2.0 mg/kg (HER2 Low Expression); 45 advanced breast cancer participants with HER2 Low Expression will be treated with RC48-ADC at a dose of 2.0 mg/kg, every 2 weeks. They will continue the medication until one of the following conditions occurred: disease progression, intolerance of toxicity, withdrawal of informed consent, or treatment for 1 year.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RP2D	Recommended Phase II Dose	Estimated 2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum Observed Plasma Concentration	Estimated 2 year
AUC	Area Under Curve	Estimated 2 year
Tmax	Time for Cmax	Estimated 2 year
Overall response Rate (ORR)	As per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 - to estimate the anti-tumor activity of RC48-ADC.	Estimated 2 year
Clinical Benefit Rate (CBR)	Clinical Benefit Rate was defined as the percentage of patients with complete remission (CR) partial remission (PR) stable (SD) not less than 4 months.	Estimated 2 year
Progression Free Survival (PFS)	Progression-free Survival (PFS) (median) was determined using the number of months measured from the initial date of treatment to the date of documented progression, or the date of death (in the absence of progression) of participants. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	Estimated 2 year

Collaborators and Investigators

• Sponsor: RemeGen Co., Ltd.
• Investigators: Study Director: Jianmin Fang, RemeGen Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2016
• Primary Completion (Actual): July 31, 2022
• Study Completion (Actual): April 7, 2023

Study Registration Dates

• First Submitted: January 4, 2017
• First Submitted That Met QC Criteria: February 9, 2017
• First Posted (Actual): February 14, 2017

Study Record Updates

• Last Update Posted (Actual): December 18, 2023
• Last Update Submitted That Met QC Criteria: December 14, 2023
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: C003 CANCER

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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