Clinical trial NCT03052634: A Study of RC48-ADC in Subjects With Advanced Breast Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Advanced Breast Cancer
Lead sponsor: RemeGen Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2017-02-14
Enrollment: 112
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: RP2D
timeFrame: Estimated 2 year
Secondary outcomes:
measure: Cmax
timeFrame: Estimated 2 year
measure: AUC
timeFrame: Estimated 2 year
measure: Tmax
timeFrame: Estimated 2 year
measure: Overall response Rate (ORR)
timeFrame: Estimated 2 year
measure: Clinical Benefit Rate (CBR)
timeFrame: Estimated 2 year
measure: Progression Free Survival (PFS)
timeFrame: Estimated 2 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Changchun
country: China
facility: The first bethune hospital of jilin unversity
state: Jilin
city: Shenyang
country: China
facility: Liaoning cancer hospital & institute
state: Liaoning
city: Hangzhou
country: China
facility: Zhejiang cancer hospital
state: Zhejiang
city: Harbin
country: China
facility: Affiliated cancer hospital of Harbin medical university
city: Hebei
country: China
facility: The fourth hospital of Hebei medical university
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
Study officials:
affiliation: RemeGen Co., Ltd.
name: Jianmin Fang
role: STUDY_DIRECTOR
References: