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

NCT04329429 | Unknown Phase 2

• 1 other identifier: RC48-C010
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 16

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.

Conditions

Biliary Tract Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR)

  24 months

Secondary Outcomes (5)

• Duration of Objective Response (DOR)

  24 months

• Progression Free Survival (PFS)

  24 months

• Overall Survival(OS)

  Up to 24 months

• Disease control rate (DCR)

  24 months

• Adverse Events

  28 days after the last dose of study treatment

Study Arms (1)

RC48-ADC

EXPERIMENTAL

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

Interventions

RC48-ADC 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)

Also known as: Recombinant Humanized anti-HER2 Monoclonal Antibody-MMAE Conjugate For Injection

RC48-ADC

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• RemeGen Co., Ltd.: lead

Study Sites (16)

Anhui Provincial Cancer Hospital

Hefei, Anhui, China

Location

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

Beijing, Beijing Municipality, China

Location

Peking University Cancer Hospital & Institute

Beijing, Beijing Municipality, China

Location

The First Hospital Affiliated to AMU (Southwest Hospital)

Chongqing, Chongqing Municipality, China

Location

Sun Yat-Sen university Cancer Center

Guangzhou, Guangdong, China

Location

Hunan Cancer Hospital

Changsha, Hunan, China

Location

First Hospital of Jilin University

Changchun, Jilin, China

Location

Shandong Cancer Hospital Affiliated to Shandong University

Jinan, Shandong, China

Location

Eastern Hepatobiliary Surgery Hospital, Second Military Medical University

Shanghai, Shanghai Municipality, China

Location

Xinhua Hospital

Shanghai, Shanghai Municipality, China

Location

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Location

Tianjin Cancer Hospital

Tianjin, Tianjin Municipality, China

Location

The First Affiliated Hospital, Zhejiang University

Hangzhou, Zhejiang, China

Location

Fudan University Shanghai Cancer Center

Shanghai, China

Location

Tongji University Shanghai East Hospital

Shanghai, China

Location

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

Injections

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Jianmin Fang, Ph.D

  RemeGen Co., Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2020
• First Posted: April 1, 2020
• Study Start: August 24, 2020
• Primary Completion: November 3, 2023
• Study Completion: June 30, 2024
• Last Updated: December 20, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (16)