A Study of HA121-28 Tablets in Advanced Biliary Tract Cancer

This study is a multicenter, open-label, single-arm phase II study to evaluate efficacy, safety, and pharmacokinetics characteristics of HA121-28 tablets in advanced biliary tract cancer (BTC). A total of approximately 30 subjects with advanced BTC will be enrolled. The subjects will undergo a 3 weeks-on and 1week-off treatment scheme with HA121-28 tablets 600 mg orally once daily in the 28-day cycle until disease progression or intolerable toxic reaction, whichever occurs first.


Eligibility Criteria:
Inclusion Criteria:

* Be willing to participate in the clinical trial and sign the informed consent;
* Histologically/cytologically confirmed unresectable locally advanced or metastatic BTC (including cholangiocarcinoma or gallbladder cancer) with failure of or intolerance to the prior therapy (including disease progression within 6 months after adjuvant chemotherapy) and with at least one measurable lesion based on RECIST 1.1 criteria;
* Aged 18 to 75 years (inclusive);
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0\~1;
* Routine blood test results must meet the following criteria without blood transfusion within 14 days: 1) Hemoglobin (Hb)≥90 g/L; 2) Absolute neutrophil count (ANC)≥1.5 x 10\^9/L; 3) Platelet count (PLT)≥75×10\^9/L;
* Coagulation test results must meet the following criteria: International Normalized Ratio (INR) \<1.5 or Activated Partial Thromboplastin Time (APTT) \<1.5×ULN;
* Other laboratory test results must meet all the following criteria: 1) Total bilirubin (TBIL)≤1.5×ULN, Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)≤2.5×ULN (TBIL≤3×ULN, ALT and AST≤5×ULN in the subjects with liver metastasis); 2) Serum creatinine≤1.5×ULN；3) Serum albumin≥28g/L;
* Male and female subjects of childbearing potential must agree to take effective contraception for the duration of treatment and for 6 months after completion of study drug administration; female subjects must have negative results of serum/urine pregnancy test within 7 days prior to enrollment and must not be breastfeeding.

Exclusion Criteria:

* Subjects with ampullary carcinoma;
* Subjects who had participated in other clinical trials and received the treatment within 4 weeks prior to enrolment;
* The time interval between the end of the last antitumor treatment and the first administration of HA121-28 tablets \< 4 weeks (for any antitumor treatment, including but not limited to chemotherapy, radiotherapy and targeted therapy), or \< 2 weeks (for local palliative radiotherapy for pain relief or traditional Chinese medicine with approved indications for cancer);
* Urine protein≥2+ and urine protein \> 1.0g/24h;
* History of other malignancies within the past 5 years prior to enrolment, except for cured cervical carcinoma in situ, non-melanoma skin cancer, superficial bladder tumor, and early esophageal and gastrointestinal cancers that were confined to the mucosal layer and resected under endoscopy;
* History of any solid-organ or bone-marrow transplantation (except the transplantation without immunosuppression such as corneal and hair transplantation);
* Unremitted toxic reaction\>grade 1 due to any previous treatment at the time of enrollment (except for hair loss and pigmentation) which is considered to influence the safety evaluation;
* ECG meets one of the following criteria: 1) QT/QTc interval≥450ms, congenital long QT syndrome (LQTS) or family history of LQTS; 2) any clinically significant abnormalities of rhythm, conduction or morphology in the resting ECG requiring therapeutic intervention;
* Left ventricular ejection fraction (LVEF) \<50% in echocardiogram;
* Severe concomitant diseases which may have influence on the safety of the subjects or the completion of the study based on the investigator' judgement such as uncontrolled hypertension (systolic pressure ≥150 mmHg or diastolic pressure ≥100 mmHg after treatment);
* High risk factors of gastrointestinal diseases such as gastrointestinal perforation and abdominal fistula;
* Subjects with spinal cord, meningeal or brain metastasis (except for asymptomatic or stable brain metastasis within 4 weeks prior to administration);
* Subjects with hepatopathy meet one of the following criteria: 1) HBsAg positive and HBV DNA \>2000 IU/mL（or \>1×10\^4 copies/mL）; 2) HCV antibody positive and HCV RNA positive; 3) cirrhosis;
* HIV antibody positive;
* Subjects have history of surgery within 4 weeks prior to administration or have not been recovered from any previous invasive procedure, except for biliary stenting, biliary drainage, etc.;
* Not suitable for the study in the investigator's opinion.