A Study of RC48-ADC in Subjects With HER2 Overexpressed Metastatic Biliary Tract Cancer

NCT ID: NCT04329429

Last Updated: 2023-12-20

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-24
• Study Completion Date: 2024-06-30

Brief Summary

This study will evaluate the efficacy and safety of intravenous RC48-ADC in patients with locally advanced or metastatic HER2 overexpressed biliary tract cancer who have failed first-line chemotherapy.

Detailed Description

This study will evaluate the efficacy and safety of intravenous RC48-ADC in patients with locally advanced or metastatic HER2 overexpressed biliary tract cancer who have failed first-line chemotherapy.

Conditions

Biliary Tract Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RC48-ADC

Participants will be treated with RC48-ADC 2.5 mg/kg, once every 2 weeks (Q2W) until investigator-assessed loss of clinical benefit, unacceptable toxicity, investigator or participant's decision to withdraw from therapy, or death (whichever occurs first)

Group Type: EXPERIMENTAL

RC48-ADC

Intervention Type: DRUG

The eligible patients will be treated with RC48-ADC, an antibody-drug conjugate, 2.5 mg/kg, once every two weeks until investigator-assessed loss of clinical benefit, unacceptable toxicity, investigator or participant's decision to withdraw from therapy, or death (whichever occurs first)

Interventions

RC48-ADC

The eligible patients will be treated with RC48-ADC, an antibody-drug conjugate, 2.5 mg/kg, once every two weeks until investigator-assessed loss of clinical benefit, unacceptable toxicity, investigator or participant's decision to withdraw from therapy, or death (whichever occurs first)

Intervention Type: DRUG

Other Intervention Names

Recombinant Humanized anti-HER2 Monoclonal Antibody-MMAE Conjugate For Injection

Eligibility Criteria

Inclusion Criteria

• Voluntary agreement to provide written informed consent.
• Male or female, Age ≥ 18 years.
• Predicted survival ≥ 12 weeks.
• Diagnosed with histologically or cytologically-confirmed locally advanced or metastatic biliary tract cancer, including extra- or intra-hepatic bile duct cancer, gallbladder cancer, and ampulla cancer.
• Patients who have previously failed first-line chemotherapy. First-line chemotherapy failure is defined as disease progression (with imaging evidence of disease progression) during or within three months after treatment based on a two-drug combination of gemcitabine, platinum, or fluorouracil, or patients still cannot tolerate drug toxicity after two standardized drug reductions, or the disease progresses or relapses during neoadjuvant / adjuvant therapy or within six months after the end of treatment.
• At least one measurable lesion according to RECIST 1.1. The measurable lesion has not been treated with local treatment, including local radiotherapy, ablation and interventional treatment.
• HER2 overexpression (i.e. IHC 2+or 3+) as confirmed by the central laboratory. Subject is able to provide specimens from primary or metastatic lesions for HER2 tests.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Adequate organ function, evidenced by the following laboratory results:

Left ventricular ejection fraction ≥ 50 %. Hemoglobin (HGB) ≥ 90 g/L; WBC count≥ 3.0×10^9/L; Neutrophil count ≥ 1.5×10^9/L; Platelets ≥ 80×10^9/L.

Total bilirubin ≤ 1.5× ULN; AST and ALT ≤ 2.5×ULN or ≤ 5 x ULN with hepatic metastasis; Serum creatinine ≤1.5×ULN, or ≥ 50 ml/min of creatinine clearance (CrCl) according to Cockcroft-Gault formula.

• All female subjects will be considered to be of child-bearing potential unless they are postmenopausal, or have been sterilized surgically.Female subjects of child-bearing potential must agree to use at least one form of highly effective contraception. Female subjects must have serum pregnancy test negative within 7 days before study enrollment and must be non-lactating. Male subjects and their female partner who are of child-bearing potential must agree to use at least one form of highly effective contraception.
• Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.

Exclusion Criteria

• Received chemotherapy (treated with nitrosourea and mitomycin C within 6 weeks, oral fluorouracil within 2 weeks), radiotherapy (palliative local radiotherapy for bone metastases within 2 weeks before dosing), targeted therapy (the elution period of small molecule targeted drug is 2 weeks or 5 half-lives, whichever is longer), immunotherapy, or Chinese traditional medicine therapy (used Chinese traditional medicine with anti-tumor indications within one week) within 4 weeks before enrollment.
• Patients with biliary obstruction were excluded, unless the biliary obstruction was locally treated, such as endoscopic stent implantation, percutaneous liver puncture drainage, etc., with total bilirubin is reduced to 1.5 times of ULN.
• Have a history of malignancies other than biliary malignancies (except cured cervical carcinoma in situ or basal cell carcinoma of the skin and other malignancies that have been cured for 5 years).
• Previously received the treatment of other antibody-drug conjugates, e.g. T-DM1 and SGN-35.
• Have central nervous system (CNS) metastases and / or cancerous meningitis. Subjects who have received brain metastasis treatment may consider participating in this study, provided that the condition is stable for at least 6 months, and no disease progression has been confirmed by imaging examination within 4 weeks before administration, and all neurological symptoms have returned to baseline Level, no evidence of new or enlarged brain metastases, and discontinuation of radiation, surgery, or steroid treatment at least 28 days before the first dose of study treatment. This exception does not include cancerous meningitis, which should be ruled out regardless of its clinical status.
• Have severe, uncontrollable companion diseases, including combined uncontrollable infections, active tuberculosis, uncontrollable diabetes, and cardiovascular disease (New York Heart Association classification of Grade III or Grade IV heart failure, above Grade II cardiac conduction blockage, myocardial infarction, unstable arrhythmia or unstable angina in the past 12 months, cerebral infarction within 6 months, etc.), lung disease (History of interstitial pneumonia, obstructive pulmonary disease, and symptomatic bronchi spasm), deep vein thrombosis or pulmonary embolism within 12 months, decompensated liver cirrhosis.
• Have active autoimmune diseases that require systemic treatment (such as disease-modifying drugs, corticosteroids, or immunosuppressive drugs) in the past 2 years, the related alternative treatments (such as thyroxine, insulin, or adrenal or pituitary insufficiency corticosteroid replacement therapy) are permitted.
• Toxicity of previous anti-tumor treatment not recovered to CTCAE Grade 0-1 (with exception of Grade 2 alopecia), except for those who have hair loss, pigmentation, anemia, weakness and those who cannot recover from the long-term toxicity caused by radiotherapy.
• HIV positive; HBsAg positive with HBV-DNA positive (≥2000 copies/ml); HCV positive, except for patients with HCV positive and HCV-RNA negative in PCR test.
• History of major surgery within 4 weeks of planned start of trial treatment, or patients with previous allogeneic hematopoietic stem cell transplant or organ transplant.
• Has received anti-cancer vaccine within 4 weeks of planned start of trial treatment, or planned to receive anti-cancer vaccine during trial treatment.
• Pleural or abdominal effusion with clinical symptoms that requires ongoing treatment.
• Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

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

Sponsors

RemeGen Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jianmin Fang, Ph.D

Role: STUDY_DIRECTOR

RemeGen Co., Ltd.

Locations

Anhui Provincial Cancer Hospital

Hefei, Anhui, China

Beijing 302 Hospital/5th Medical Center of Chinese PLA General of Hospital

Beijing, Beijing Municipality, China

Peking University Cancer Hospital & Institute

Beijing, Beijing Municipality, China

The First Hospital Affiliated to AMU (Southwest Hospital)

Chongqing, Chongqing Municipality, China

Sun Yat-Sen university Cancer Center

Guangzhou, Guangdong, China

Hunan Cancer Hospital

Changsha, Hunan, China

First Hospital of Jilin University

Changchun, Jilin, China

Shandong Cancer Hospital Affiliated to Shandong University

Jinan, Shandong, China

Eastern Hepatobiliary Surgery Hospital, Second Military Medical University

Shanghai, Shanghai Municipality, China

Xinhua Hospital

Shanghai, Shanghai Municipality, China

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, China

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Tianjin Cancer Hospital

Tianjin, Tianjin Municipality, China

The First Affiliated Hospital, Zhejiang University

Hangzhou, Zhejiang, China

Fudan University Shanghai Cancer Center

Shanghai, , China

Tongji University Shanghai East Hospital

Shanghai, , China

Countries

China

Other Identifiers

RC48-C010

Identifier Type: -

Identifier Source: org_study_id