Overview

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

Status:
Recruiting
Trial end date:
2023-12-31
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
RemeGen
RemeGen Co., Ltd.
Treatments:
Antibodies
Trastuzumab
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.