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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT04329429
Recruitment Status : Recruiting
First Posted : April 1, 2020
Last Update Posted : September 16, 2021
Information provided by (Responsible Party):
RemeGen Co., Ltd.

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.

Condition or disease Intervention/treatment Phase
Biliary Tract Cancer Drug: RC48-ADC Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 57 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Single-arm, Multi-center, Phase II Study of RC48-ADC in Subjects With HER2 Overexpressed Locally Advanced or Metastatic Biliary Tract Cancer (BTC) Who Have Failed First-line Chemotherapy
Actual Study Start Date : August 24, 2020
Estimated Primary Completion Date : August 1, 2023
Estimated Study Completion Date : December 31, 2023

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: 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)
Drug: 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)
Other Name: Recombinant Humanized anti-HER2 Monoclonal Antibody-MMAE Conjugate For Injection

Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: 24 months ]
    Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR)

Secondary Outcome Measures :
  1. Duration of Objective Response (DOR) [ Time Frame: 24 months ]
    DOR was defined as the time from first documented OR to first documented PD or death from any cause, whichever occurred earlier

  2. Progression Free Survival (PFS) [ Time Frame: 24 months ]
    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.

  3. Overall Survival(OS) [ Time Frame: Up to 24 months ]
    OS was defined as the time from the first study treatment to the date of death from any cause.

  4. Disease control rate (DCR) [ Time Frame: 24 months ]
    DCR was defined as the proportion of patients who achieved an objective response or maintained stable disease

  5. Adverse Events [ Time Frame: 28 days after the last dose of study treatment ]
    Incidence of Adverse Events

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04329429

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Contact: Xiaohong Su, MD 086-13910166369 xiaohong.su@remegen.cn

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China, Anhui
Anhui Provincial Cancer Hospital Recruiting
Hefei, Anhui, China
Contact: Yifu He, M.D.         
China, Beijing
Beijing 302 Hospital/5th Medical Center of Chinese PLA General of Hospital Recruiting
Beijing, Beijing, China
Contact: Yinying Lu, M.D.         
Peking University Cancer Hospital & Institute Recruiting
Beijing, Beijing, China
Contact: Chunyi Hao, M.D.         
China, Chongqing
The First Hospital Affiliated to AMU (Southwest Hospital) Recruiting
Chongqing, Chongqing, China
Contact: Houjie Liang, M.D.         
China, Guangdong
Sun Yat-Sen university Cancer Center Recruiting
Guangzhou, Guangdong, China
Contact: Yajin Chen, M.D.         
China, Hunan
Hunan Cancer Hospital Recruiting
Changsha, Hunan, China
Contact: Shanzhi Gu, M.D.         
Hunan Cancer Hospital Recruiting
Changsha, Hunan, China
Contact: Ruocai Xu, M.D.         
China, Jilin
First Hospital of Jilin University Recruiting
Chang chun, Jilin, China
Contact: Wei Li, M.D.         
China, Shandong
Shandong Cancer Hospital Affiliated to Shandong University Recruiting
Jinan, Shandong, China
Contact: Zuoxing Niu, M.D.         
China, Shanghai
Eastern Hepatobiliary Surgery Hospital, Second Military Medical University Recruiting
Shanghai, Shanghai, China
Contact: Heping Hu, M.D.         
Xinhua Hospital Recruiting
Shanghai, Shanghai, China
Contact: Yingbin Liu, M.D.         
Zhongshan Hospital, Fudan University Recruiting
Shanghai, Shanghai, China
Contact: Lan Zhang, M.D.         
China, Sichuan
West China Hospital, Sichuan University Recruiting
Chengdu, Sichuan, China
Contact: Shuang Zhang, M.D.         
China, Tianjin
Tianjin Cancer Hospital Recruiting
Tianjin, Tianjin, China
Contact: Tianqiang Song, M.D.         
China, Zhejiang
The First Affiliated Hospital, Zhejiang University Recruiting
Hangzhou, Zhejiang, China
Contact: Weijia Fang, M.D.         
Fudan University Shanghai Cancer Center Recruiting
Shanghai, China
Contact: Zhiqiang Meng, MD         
Tongji University Shanghai East Hospital Recruiting
Shanghai, China
Contact: Jin Li, MD    086-13761222111    lijin@csco.org.cn   
Sponsors and Collaborators
RemeGen Co., Ltd.
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Responsible Party: RemeGen Co., Ltd.
ClinicalTrials.gov Identifier: NCT04329429    
Other Study ID Numbers: RC48-C010
First Posted: April 1, 2020    Key Record Dates
Last Update Posted: September 16, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Biliary Tract Diseases
Digestive System Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents