A Trial of SHR1258 in Patients With Biliary Tract Cancer

Inclusion Criteria:

• enrollment into the study:

  1. Signed and dated written informed consent which is approved by Institutional Review Board (IRB)/Ethics Committee (EC), willing and able to comply with scheduled treatment, all examinations at study visits, and other study procedures.
  2. Male or female, ≥18 years old.
  3. Histologically or cytologically confirmed (at a local laboratory) BTC
  4. Received up to two prior regimen of systemic therapy for advanced disease, including 1 gemcitabine-containing regimen, and experienced disease progression after or developed intolerance to the most recent prior therapy.
  5. Sufficient tumor tissue samples (archival or fresh biopsy samples) will be provided by all subjects prior to the administration of pyrotinib (for retrospective confirmation of HER2 alteration through a central laboratory if applicable).
  6. Must have measureable disease per RECIST v1.1. The definition of CT or MRI measurable lesion as the target lesion: according to RECIST v1.1, the long diameter of such lesion should be ≥ 10 mm by the CT scan or the short diameter of enlarged lymph nodes ≥ 15 mm.
  7. The laboratory test values must meet the functional level of important organs/systems meets
  8. ECOG-PS (see Appendix 2): 0 - 1.
  9. If subjects have active hepatitis B virus (HBV) infection: HBV- deoxyribonucleic acid (DNA) must be \< 500 IU/mL and are willing to receive antiviral therapy throughout the study; subjects with positive hepatitis C (HCV) ribonucleic acid (RNA) must receive antiviral therapy in accordance with the local standard treatment guideline and have ≤ CTCAE Grade 1 elevated hepatic function.
  10. Women of childbearing potential (WOCBP) must have a serum pregnancy test within 7 days before the first dose and the result is negative. WOCBP and male subjects whose partners are WOCBP must agree to use effective contraception method during the study period and within 8 weeks after the last dose of study medication.

Exclusion Criteria:

• Inclusion Criteria:

Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:

1. Signed and dated written informed consent which is approved by Institutional Review Board (IRB)/Ethics Committee (EC), willing and able to comply with scheduled treatment, all examinations at study visits, and other study procedures.
2. Male or female, ≥18 years old.
3. Histologically or cytologically confirmed (at a local laboratory) BTC
4. Received up to two prior regimen of systemic therapy for advanced disease, including 1 gemcitabine-containing regimen, and experienced disease progression after or developed intolerance to the most recent prior therapy.
5. Sufficient tumor tissue samples (archival or fresh biopsy samples) will be provided by all subjects prior to the administration of pyrotinib (for retrospective confirmation of HER2 alteration through a central laboratory if applicable).
6. Must have measureable disease per RECIST v1.1. The definition of CT or MRI measurable lesion as the target lesion: according to RECIST v1.1, the long diameter of such lesion should be ≥ 10 mm by the CT scan or the short diameter of enlarged lymph nodes ≥ 15 mm.
7. The laboratory test values must meet the functional level of important organs/systems meets
8. ECOG-PS (see Appendix 2): 0 - 1.
9. If subjects have active hepatitis B virus (HBV) infection: HBV- deoxyribonucleic acid (DNA) must be \< 500 IU/mL and are willing to receive antiviral therapy throughout the study; subjects with positive hepatitis C (HCV) ribonucleic acid (RNA) must receive antiviral therapy in accordance with the local standard treatment guideline and have ≤ CTCAE Grade 1 elevated hepatic function.
10. Women of childbearing potential (WOCBP) must have a serum pregnancy test within 7 days before the first dose and the result is negative. WOCBP and male subjects whose partners are WOCBP must agree to use effective contraception method during the study period and within 8 weeks after the last dose of study medication.

Exclusion Criteria:

Subjects presenting with any of the following will not be enrolled into the study:

1. Prior receipt of HER2-targeted therapy.
2. Concurrent anticancer therapy, other than the therapies being tested in this study.
3. Radiation therapy administered within 2 weeks of first dose of study treatment.
4. Laboratory values at screening outside the protocol-defined range.
5. Clinically significant or uncontrolled cardiac disease.
6. Target disease exclusion criteria:

1) Malignant tumors with other pathological types, such as mixed cancer, double primary cancers.

2) Medical history of other active malignancies within last 5 years. 3) Subjects with active central nervous system (CNS) metastases are excluded. Subjects with history or evidence of current leptomeningeal metastases are excluded.

4) By the date of first dose of study treatment, the washout period of previous drug treatment / medical intervention does not meet the following requirements 7. Medical history exclusion criteria:

1. Severe cardiac disease
2. Prior to the first dose of study treatment, patients with the following conditions: inability to swallow, chronic diarrhea, intestinal obstruction, gastrointestinal perforation or gastrectomy, colitis or other diseases or special conditions that affect drug administration and absorption.
3. Prior to the first dose of study treatment, patients with severe effusions with clinical symptoms
4. Symptoms of severe infection or evidence for microbiological/viral diagnosis.
5. Congenital or acquired immunodeficiency (e.g., human immunodeficiency virus [HIV] infection).

8. History of allergy to the study drugs or components. 9. Pregnancy or breastfeeding. 10. Concomitant treatments exclusion criteria:

1. Within 2 weeks prior to the first dose of study treatment, or during the study period, patients receive or are anticipated to receive continuous strong CYP3A4 inducers or inhibitors, P-gp inhibitors.

11. Others:

1. Per investigator's judgment, other diseases or laboratory evidence that would cause serious threats to the safety of the patients, or which are not in the best interest of the patient to participate in the study are excluded
2. Per investigator's judgment, other situations that may confuse the study results or would affect the subjects' ability to comply with study procedures are excluded, such as alcoholism, drug abuse, criminal detention, etc.