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

NCT03052634 | Completed Phase 1

• 1 other identifier: C003 CANCER
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 7

Brief Summary

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

Conditions

Advanced Breast Cancer

Outcome Measures

Primary Outcomes (1)

• RP2D

  Recommended Phase II Dose

  Estimated 2 year

Secondary Outcomes (6)

• Cmax

  Estimated 2 year

• AUC

  Estimated 2 year

• Tmax

  Estimated 2 year

• Overall response Rate (ORR)

  Estimated 2 year

• Clinical Benefit Rate (CBR)

  Estimated 2 year

Study Arms (4)

RC48-ADC 1.5 mg/kg (HER2 Positive)

EXPERIMENTAL

Drug: RC48-ADC 1.5 mg/kg (HER2 Positive)

RC48-ADC 2.0 mg/kg (HER2 Positive)

EXPERIMENTAL

Drug: RC48-ADC 2.0 mg/kg (HER2 Positive)

RC48-ADC 2.5 mg/kg (HER2 Positive)

EXPERIMENTAL

Drug: RC48-ADC 2.5 mg/kg (HER2 Positive)

RC48-ADC 2.0 mg/kg (HER2 Low Expression)

EXPERIMENTAL

Drug: RC48-ADC 2.0 mg/kg (HER2 Low Expression)

Interventions

RC48-ADC 1.5 mg/kg (HER2 Positive) DRUG

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.

RC48-ADC 1.5 mg/kg (HER2 Positive)

RC48-ADC 2.0 mg/kg (HER2 Positive) DRUG

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.

RC48-ADC 2.0 mg/kg (HER2 Positive)

RC48-ADC 2.5 mg/kg (HER2 Positive) DRUG

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.

RC48-ADC 2.5 mg/kg (HER2 Positive)

RC48-ADC 2.0 mg/kg (HER2 Low Expression) DRUG

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.

RC48-ADC 2.0 mg/kg (HER2 Low Expression)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary signed informed consent;
• Female, aged between 18 to 70 years;
• ECOG performance status score of 0 or 1;
• Life expectancy greater than 12 weeks；
• Patients with locally advanced or metastatic breast cancer diagnosed by histology or cytology, and:
• 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;
• 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;
• Measurable lesion according to the RECIST 1.1;
• 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%.

You may not qualify if:

• Women who are pregnant (positive blood test before medication) or breastfeeding;
• 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;
• 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;
• Received Palliative radiation therapy for bone metastases within 2 weeks before study drug treatment;
• Toxicity of previous anti-tumor treatment has not recovered to CTCAE \[version 4.0\] 0-1, except for hair loss;
• Participated in other clinical trials within 4 weeks;
• Known hypersensitivity or delayed hypersensitivity to the some components of RC48-ADC or similar drugs;
• The active infection with clinical significance according to the researcher's judgment;
• Diagnosed with HBsAg or HBcAb positive and HBV DNA positive, or HCV Ab positive, or HIV Ab positive.
• Have a history of immunodeficiency, including a positive HIV test, or other acquired, congenital immunity Epidemic defects, or a history of organ transplantation;
• Uncontrolled systemic diseases such as diabetes, hypertension, Pulmonary fibrosis, acute lung disease, interstitial lung disease, etc.
• 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 ;
• Insufficient adherence to participate in this clinical study;
• 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 );
• Primary brain or metastatic tumor;

Sponsors & Collaborators

• RemeGen Co., Ltd.: lead

Study Sites (7)

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

Location

The first bethune hospital of jilin unversity

Changchun, Jilin, China

Location

Liaoning cancer hospital & institute

Shenyang, Liaoning, China

Location

Zhejiang cancer hospital

Hangzhou, Zhejiang, China

Location

Affiliated cancer hospital of Harbin medical university

Harbin, China

Location

The fourth hospital of Hebei medical university

Hebei, China

Location

Jiangsu Cancer Hospital

Nanjing, China

Location

Study Officials

• Jianmin Fang

  RemeGen Co., Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2017
• First Posted: February 14, 2017
• Study Start: December 23, 2016
• Primary Completion: July 31, 2022
• Study Completion: April 7, 2023
• Last Updated: December 18, 2023

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (7)