Clinical trial NCT04329429: A Study of RC48-ADC in Subjects With HER2 Overexpressed Metastatic Biliary Tract Cancer
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Biliary Tract Cancer
Lead sponsor: RemeGen Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-04-01
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 24 months
Secondary outcomes:
measure: Duration of Objective Response (DOR)
timeFrame: 24 months
measure: Progression Free Survival (PFS)
timeFrame: 24 months
measure: Overall Survival(OS)
timeFrame: Up to 24 months
measure: Disease control rate (DCR)
timeFrame: 24 months
measure: Adverse Events
timeFrame: 28 days after the last dose of study treatment
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Cancer Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing 302 Hospital/5th Medical Center of Chinese PLA General of Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Cancer Hospital & Institute
state: Beijing
city: Chongqing
country: China
facility: The First Hospital Affiliated to AMU (Southwest Hospital)
state: Chongqing
city: Guangzhou
country: China
facility: Sun Yat-Sen university Cancer Center
state: Guangdong
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Chang chun
country: China
facility: First Hospital of Jilin University
state: Jilin
city: Jinan
country: China
facility: Shandong Cancer Hospital Affiliated to Shandong University
state: Shandong
city: Shanghai
country: China
facility: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University
state: Shanghai
city: Shanghai
country: China
facility: Xinhua Hospital
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital, Fudan University
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University
state: Zhejiang
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shanghai
country: China
facility: Tongji University Shanghai East Hospital
Study officials:
affiliation: RemeGen Co., Ltd.
name: Jianmin Fang, Ph.D
role: STUDY_DIRECTOR
References: