A Study of RC48-ADC Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer With or Without Liver Metastases

NCT ID: NCT03500380

Last Updated: 2024-02-20

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 301 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-24
• Study Completion Date: 2024-12-31

Brief Summary

This is a randomized, open, parallel-controlled, multicenter, phase II/III, seamless design clinical trial to compare the efficacy and safety of RC48-ADC with capecitabine + lapatinib in locally advanced or metastatic human epidermal growth factor receptor 2 (HER2) positive breast cancer and HER2-positive advanced breast cancer with liver metastasis.

Conditions

Breast Neoplasms; Breast Diseases; Capecitabine; HER2-positive Breast Cancer; HER2 Positive Breast Carcinoma; HER2-positive Advanced Breast With Liver Metastases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RC48-ADC

Participants will receive RC48-ADC 2.0 mg/kg intravenous (IV) infusion each 14-day treatment cycle until disease progression (PD) (as assessed by the investigator), unmanageable toxicity, or study termination.

Group Type: EXPERIMENTAL

RC48-ADC

Intervention Type: DRUG

RC48-ADC 2.0 mg/kg IV every 14 days

Lapatinib + Capecitabine

Participants will receive lapatinib 1250 mg orally once daily during each 21-day cycle + capecitabine 2000 mg/m\^2 orally daily on Days 1-14 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination.

Group Type: ACTIVE_COMPARATOR

Lapatinib

Intervention Type: DRUG

Lapatinib 1250 mg orally once daily during each 21-day cycle.

Capecitabine

Intervention Type: DRUG

Capecitabine 2000 mg/m\^2 orally daily on Days 1-14 of each 21-day treatment cycle.

Interventions

RC48-ADC

RC48-ADC 2.0 mg/kg IV every 14 days

Intervention Type: DRUG

Lapatinib

Lapatinib 1250 mg orally once daily during each 21-day cycle.

Intervention Type: DRUG

Capecitabine

Capecitabine 2000 mg/m\^2 orally daily on Days 1-14 of each 21-day treatment cycle.

Intervention Type: DRUG

Other Intervention Names

RC48

Eligibility Criteria

Inclusion Criteria

• Voluntarily agree to participate in the study and sign the informed consent form.
• Subjects aged 18 - 70 years (inclusive), and the subject who have not reached the age of 71 years old will be considered to be ≤ 70 years of age.
• Expected survival ≥ 12 weeks.
• ECOG PS score 0 or 1.
• Female subjects should be surgically sterilized or in post-menopausal status, or agree to use at least one medically accepted contraceptive methods (such as intrauterine device, contraceptive drug or condom) during study treatment period and for up to 6 months after the study treatment is completed, and the blood pregnancy test must be negative within 7 days prior to study enrollment, and they must not be lactating. For male subjects: all the subjects should be surgically sterilized or agree to use one of the medically approved contraceptive methods during the study treatment period and for an additional of 6 months after the end of the study treatment period.
• Able to understand study requirements, willing and able to comply with study protocol and follow-up procedures.

With Adequate Organ Function

• Bone marrow function:

Hemoglobin ≥ 9 g/dL; Absolute neutrophil count ≥ 1.5×109/L; Platelets ≥ 100 × 109/L;

• Liver function (based on the normal values specified by study site):

Serum total bilirubin ≤ 1.5 × the upper limit of normal (ULN); Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) ≤ 2.5 × ULN in the absence of liver metastases, while ALT, AST and ALP ≤ 5 × ULN in the presence of liver metastases;

• Renal function (based on the normal values specified by study site):

Serum creatinine ≤ 1.5 × ULN, or creatinine clearance (CrCl) ≥ 60 mL/min as calculated by Cockcroft-Gault formula, or 24-hour urine Crcl ≥ 60 mL/min;

• Cardiac function:

New York Heart Association (NYHA) classification < Grade III; Left ventricular ejection fraction ≥ 50%; Tumor Related Criteria

• Histologically and/or cytologically confirmed invasive locally advanced or metastatic breast cancer that is incurable and unresectable;
• Positive HER2 expression (positive defined as: IHC 3+ or FISH+); previous test results of HER2 expression provided by the subjects (have to be confirmed by the investigator) and those obtained from the study site or the central laboratory were both acceptable; subject are able to provide samples from primary or metastatic tumor sites for HER2 test (either paraffin blocks, paraffin-embedded sections, or sections prepared using freshly excised tissues);
• With prior taxane therapy (monotherapy or in combination with other drugs, treatment duration should be ≥ 2 cycles);
• With prior adjuvant therapy, have received treatment with trastuzumab or its biosimilar for patients with locally advanced cancer or metastasis during relapse and metastasis (monotherapy or in combination with other drugs, such as for ≥ 3 months in the adjuvant therapy phase, and ≥ 6 weeks in the post-relapse and metastatic phase);
• With evidence of tumor progression during or after the most recent treatment as confirmed by the investigator or with documented history;
• No more than 2 lines of chemotherapy received after relapse/metastasis. The number of chemotherapy lines is restricted to chemotherapeutic drugs, and each chemotherapy regimen is counted as a number of chemotherapy line, excluding targeted drugs and/or endocrine drugs; the same maintenance treatment as the previous chemotherapy regimen will not be counted.
• With at least one measurable lesion per RECIST v1.1.

• Had previously participated in the study of randomized controlled period and received lapatinib plus capecitabine, and received no anti-tumor treatment after disease progression (RECIST v1.1 criteria);
• The general situation part refers to the selection criteria of the first stage randomized control period.

• The general situation part refers to the selection criteria of the first stage randomized control period.

• Had previously participated in the study of randomized controlled period and received lapatinib plus capecitabine, and received no anti-tumor treatment after disease progression (RECIST v1.1 criteria);
• Expected survival ≥ 12 weeks;
• ECOG PS score 0 or 1;
• Female subjects should be surgically sterilized or in post-menopausal status, or agree to use at least one medically accepted contraceptive methods (such as intrauterine device, contraceptive drug or condom) during study treatment period and for up to 6 months after the study treatment is completed, and the blood pregnancy test must be negative within 7 days prior to study enrollment, and they must not be lactating. For male subjects: all the subjects should be surgically sterilized or agree to use one of the medically approved contraceptive methods during the study treatment period and for an additional of 6 months after the end of the study treatment period.
• Able to understand study requirements, willing and able to comply with study protocol and follow-up procedures.

With Adequate Organ Function

• Bone marrow function:

Hemoglobin ≥ 9 g/dL; Absolute neutrophil count ≥ 1.5×109/L; Platelets ≥ 100 × 109/L;

• Liver function (based on the normal values specified by study site):

Serum total bilirubin ≤ 1.5 × the upper limit of normal (ULN); Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) ≤ 2.5 × ULN in the absence of liver metastases, while ALT, AST and ALP ≤ 5 × ULN in the presence of liver metastases;

• Renal function (based on the normal values specified by study site):

Serum creatinine ≤ 1.5 × ULN, or creatinine clearance (CrCl) ≥ 60 mL/min as calculated by Cockcroft-Gault formula, or 24-hour urine Crcl ≥ 60 mL/min;

• Cardiac function:

New York Heart Association (NYHA) classification < Grade III; Left ventricular ejection fraction ≥ 50%;

Exclusion Criteria

• Use of investigational drugs within 4 weeks prior to study treatment;
• Have received major surgeries within 4 weeks prior to study treatment and have not recovered yet;
• Have received a live vaccine inoculation within 4 weeks prior to the start of study drug administration or was scheduled to receive any vaccine during the study;
• Have experienced arterial/venous thromboembolic events, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis and pulmonary embolism within 1 year prior to the initiation of study treatment;
• Suffering uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung disease, interstitial lung disease, cirrhosis, etc.;
• Currently suffering from active infections requiring systemic treatment;
• With history of active tuberculosis;
• With positive HIV test result;
• Patients with active hepatitis B or C (HBsAg positive and HBV DNA positive; HCVAb positive);
• Presence of effusion in the third space (including massive hydrothorax or ascites) that cannot be controlled by drainage or other methods;
• With known hypersensitivity or delayed-type hypersensitivity to certain components of RC48-ADC, capecitabine, lapatinib or similar drugs;
• With pre-existing gastrointestinal disorders that may affect absorption, such as ileus, ulcerative colitis, chronic diarrhea, inability to swallow, and other conditions that may affect drug administration and absorption;
• With known psychiatric disorders or drug abuse disorders that might have an impact on compliance with protocol requirements;
• Have any other diseases, metabolic disorders, abnormal physical examination findings or abnormal laboratory test results, which, judged by the investigator, are reasonably to suspect a disease or condition as a contraindication of the study drug, or may interfere the interpretation of the study results in the future, or that put the patient at a high risk;
• Women who are pregnant or during lactation period or women/men with childbearing plans;
• Subjects who are estimated to have poor compliance with the clinical study or the investigator determines that there are other factors not appropriate to participate in the study;
• Presence of brain metastases and/or carcinomatous meningitis.
• Had any other malignancy within 5 years prior to signing of the informed consent (except for non-melanoma skin cancer, cervix carcinoma in situ or other tumor that have been effectively treated and considered to be cured);
• Have received prior chemotherapy, radiotherapy, immunotherapy within 4 weeks prior to the first dose of the study drug;
• Have received hormonal therapy for breast cancer within 2 weeks prior to the start of study treatment;
• Patients who received palliative radiotherapy for bone metastases within 2 weeks before the start of study treatment;
• Have received anti-tumor traditional Chinese medicine within 2 weeks prior to the start of study treatment;
• Have received capecitabine within 6 months prior to the start of study treatment, or have failed to respond to prior treatment with capecitabine (including progression while on capecitabine treatment or maintenance of clinical efficacy for a period of less than 6 months after treatment), or with intolerance to capecitabine. Patients who have received capecitabine as adjuvant therapy and have discontinued this therapy for ≥ 6 months are eligible;
• The toxicity of prior anti-tumor therapy had not recovered to CTCAE [Version 4.03] Grade 0-1, with the following exceptions: a). alopecia; b). pigmentation; c). long-term toxicity caused by radiotherapy, which are considered as irreversible by the investigator;
• With prior systemic therapy with or participation in clinical studies with HER2 tyrosine kinase inhibitors (TKIs);
• With prior treatment with T-DM1 or had participated in clinical studies with same class of drugs.
• With known hypersensitivity to 5-fluorouracil or known dihydropyrimidine dehydrogenase deficiency.

• Have received major surgeries within 4 weeks prior to study treatment and have not recovered yet;
• Have received a live vaccine inoculation within 4 weeks prior to the start of study drug administration or was scheduled to receive any vaccine during the study (except the COVID-19 vaccine);
• Have experienced arterial/venous thromboembolic events, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis and pulmonary embolism within 1 year prior to the initiation of study treatment;
• Suffering uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung disease, interstitial lung disease, cirrhosis, etc.;
• Currently suffering from active infections requiring systemic treatment;
• With positive HIV test result;
• Patients with active hepatitis B or C (HBsAg positive and HBV DNA positive; HCVAb positive);
• Presence of effusiona in the third space (including massive hydrothorax or ascites) that cannot be controlled by drainage or other means;
• With known hypersensitivity or delayed-type hypersensitivity to certain components of RC48-ADC or similar drugs;
• With known psychiatric disorders or drug abuse disorders that might have an impact on compliance with protocol requirements;
• Have any other diseases, metabolic disorders, abnormal physical examination findings or abnormal laboratory test results, which, judged by the investigator, are reasonably to suspect a disease or condition as a contraindication of the study drug, or may interfere the interpretation of the study results in the future, or that put the patient at a high risk;
• Women who are pregnant or in lactation period or women/men with childbearing plans;
• Subjects who are estimated to have poor compliance with the protocol of this cross-over period or the investigator determines that there are other factors not appropriate to participate in the study;
• Presence of brain metastases and/or carcinomatous meningitis. Have received prior treatment for brain metastases may be considered for participating in this study, provided that the diseases were stable, had no disease progression as confirmed by imaging examinations within 4 weeks prior to the first dose of the investigational product (IP), and that all neurological symptoms have recovered to baseline level without any evidence of newly emerging or spread brain metastases; moreover, treatment with radiation, surgery or steroids was discontinued at least 14 days prior to the first dose of study drug. This exception did not include cancerous meningitis, which should be excluded regardless of the stability of its clinical status;
• Patients who received palliative radiotherapy for bone metastases within 2 weeks before the start of study treatment;
• Received treatment with lapatinib and/or capecitabine within 2 weeks prior to the first dose of the study drug;
• The toxicity of prior anti-tumor therapy had not recovered to CTCAE [Version 4.03] Grade 0-1, with the following exceptions: a). alopecia; b). pigmentation; c). long-term toxicity caused by radiotherapy, which are considered as irreversible by the investigator;

• The toxicity of prior anti-tumor therapy had not recovered to CTCAE [Version 5.0] Grade 0-1, with the following exceptions: a). alopecia; b). pigmentation; c). long-term toxicity caused by radiotherapy, which are considered as irreversible by the investigator;

• The toxicity of prior anti-tumor therapy had not recovered to CTCAE [Version 5.0] Grade 0-1, with the following exceptions: a. alopecia; b. pigmentation; c. long-term toxicity caused by radiotherapy, which are considered as irreversible by the investigator;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

RemeGen Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Liaoning Cancer Hospital & Institute

Shenyang, Liaoning, China

The First Hospital of China Medical University

Shenyang, Liaoning, China

An Yang Cancer Hospital

Anyang, , China

Beijing Luhe Hospital

Beijing, , China

Peking University People's Hospital

Beijing, , China

The First Affiliated Hospital of Bengbu Medical College

Bengbu, , China

Bin Zhou No.1 People's Hospital

Binzhou, , China

Jilin Cancer Hospital

Changchun, , China

The First Hospital Jilin University

Changchun, , China

The First Hospital of Jilin University

Changchun, , China

Hunan Cancer Hospital

Changsha, , China

The Second Xiyang Hospital of Central South University

Changsha, , China

Xiangya Hospital Central South University

Changsha, , China

Heping Hospital Affiliated to Changzhi Medical College

Changzhi, , China

Affiliated Hospital of Chengde Medical University

Chengde, , China

West China Hospital,Sichuan University

Chengdu, , China

Chongqing University Three gorges Hospital

Chongqing, , China

The Southwest Hospital of AMU

Chongqing, , China

The Second Hospital of Dalian Medical University

Dalian, , China

Fujian Cancer Hospital

Fuzhou, , China

Guangdong Provincial People's Hospital

Guangzhou, , China

Sun Yat-Sen Memorial Hospital

Guangzhou, , China

The Affiliated Tumor Hospital of Guangzhou Medical University

Guangzhou, , China

Guizhou Cancer Hospital

Guiyang, , China

The First Affiliated Hospital of Medical School of Zhejiang University

Hangzhou, , China

The Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, , China

Zhejiang Cancer Hospital

Hangzhou, , China

Harbin Medical University Cancer Hospital

Ha’erbin, , China

Anhui Cancer Hospital

Hefei, , China

Anhui Province Hospital

Hefei, , China

The First Affiliated Hospital of Anhui Medical University

Hefei, , China

Qilu Hospital of Shandong University

Jinan, , China

The First People's Hospital of Jining

Jining, , China

Yunnan Cancer Hospital

Kunming, , China

Linyi Cancer Hospital

Linyi, , China

The First Affiliated Hospital of Henan University of Science & Technology

Luoyang, , China

Jiangsu Cancer Hospital

Nanjing, , China

The Affiliated Tumor Hospital of Guangxi Medical University

Nanning, , China

The Second People's Hospital of Neijiang

Neijiang, , China

Hospital of Qingdao University

Qingdao, , China

Fudan University Shanghai Cancer Center

Shanghai, , China

Shanghai Changhai Hospital

Shanghai, , China

Shanghai Ruijin Hospital

Shanghai, , China

Cancer Hospital of Shantou University Medical College

Shantou, , China

Yue Bei People's Hospital

Shaoguan, , China

The Fourth Hospital of Hebei Medical University

Shijiazhuang, , China

Shanxi Bethune Hospital

Taiyuan, , China

Shanxi Cancer Hospital

Taiyuan, , China

Taizhou Enze Medical Center

Taizhou, , China

Tai'an City Central Hospital

Tai’an, , China

Tianjin Cancer Hospitial

Tianjin, , China

Weihai Municipal Hospital

Weihai, , China

Hubei Cancer Hospital

Wuhan, , China

Tongji Medical College of HUST

Wuhan, , China

Wuhan Union Hospital

Wuhan, , China

The First Affiliated Hospital of the Fourth Military University of P.L.A.

Xi'an, , China

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, , China

Xing Tai People's Hospital

Xingtai, , China

The First Affiliated Hospital of Xinxiang Medical University

Xinxiang, , China

The Affiliated Hospital of Xuzhou Medical University

Xuzhou, , China

Xuzhou Central Hospital

Xuzhou, , China

Yanbian University Hospital

Yanbian, , China

Yantai Yuhuangding Hospital

Yantai, , China

Yuncheng Central Hospital

Yuncheng, , China

Henan Cancer Hospital

Zhengzhou, , China

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, , China

Countries

China

Other Identifiers

RC48-C006

Identifier Type: -

Identifier Source: org_study_id