Advanced biliary tract cancer
Conditions
Interventions
Experimental group:Phase Ib(Safety run-in,N=6):Linperlisib:80mg QD oral in a 21-day cycle. Adebrelimab: 1200mg q3w intravenous drip in a 21-day cycle.
Phase II(Expansion phase, N=28): Linperlisib: RP2
Sponsors
The Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1.Ages 18-75, gender unlimited. 2.Pathologically confirmed biliary malignancy, at least one measurable lesion (according to RECIST v1.1 requirements). 3.Patients with distant metastasis or locally advanced disease, disease progression or toxicity intolerance after first-line systemic therapy. For neoadjuvant or adjuvant therapy, if disease progression occurs during treatment or within 6 months after stopping treatment, it should be counted as first-line treatment. 4.ECOG score of 0-2. 5.Child-Pugh score of A and B (=7). 6.Expected life expectancy is more than 3 months. 7.Adequate organ function: ANC=1.5×10^9/L; PLT=90×10^9/L; Hb=90 g/L; Albumin (ALB) = 3 g/dL; TBIL=1.5×Upper limit of normal value (ULN); ALT AST=2.5×ULN ; SCr=1.5×ULN or CCr = 50 mL/min ; LVEF=50%;QTcF <450 ms(male), QTcF <470 ms(female), QTc interval is calculated using the Fridericia formula. 8.The subjects voluntarily joined this study, signed an informed consent form, and cooperated with follow-up. 9.Women of childbearing age or male subjects whose sexual partner are female of reproductive age, must voluntarily use appropriate and effective methods of contraception during observation and within 6 months after the last administration of study medication;
Exclusion criteria
Exclusion criteria: 1.Known allergies to the study drug or excipients. 2.Pathological diagnosis of hepatocellular carcinoma, mixed hepatocellular carcinoma and other non-cholangiocarcinoma malignant tumor components. 3.Patients didn’t response to previous PD-1\PD-L1 antibody therapy. 4.Patients with other ongoing malignancies or other malignancies that require aggressive treatment. 5.Patients with untreated or symptomatic brain metastases. 6.Patients requiring systemic steroid or immunosuppressive therapy. 7.Patients with active viral, bacterial or fungal infection that requires treatment. 8.Patients with a risk of gastrointestinal bleeding are not eligible for enrollment, including: (1) active peptic ulcer lesions and fecal occult blood (++); (2) Individuals with a history of black stools and vomiting blood within 2 months. 9.Patients received target lesion radiotherapy within 4 weeks prior to the first dose of study therapy. 10.Hepatic encephalopathy , hepatorenal syndrome, Child-Pugh score of B (>7) or more severe cirrhosis. 11.Has a history or current evidence of any condition, laboratory abnormality or other circumstances that might confound the results of the study or interfere with participation for the full duration of the study, such that it is not in the best interests of the patient to take part in the study. 12.Pregnant or lactating women, or a pregnancy test with a positive result . 13.Medical history of immunodeficiency syndrome (AIDS)-defining illness, including Human immunodeficiency virus (HIV) infection, or allogeneic bone marrow/stem cells transplant or organ transplant. 14.Has clinically significant cardiovascular disease: grade III or IV heart failure as defined by the New York Heart Association scale heart block above degree ? myocardial infarction within the past 6 months unstable arrhythmia or unstable angina pectoris cerebral infarction occurred within 3 months. 15.Medical history of other primary malignant tumors in the past 5 years, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, papillary thyroid carcinoma, Localized low-risk prostate cancer or carcinoma in situ (e.g., breast, cervical cancer in situ) who have undergone curative therapy with no evidence of recurrence. 16.Active hepatitis B and C infection (HbsAg and/or HbcAb positive and HBV-DNA positive; Hepatitis C antibody positive and HCV-RNA positive) 17.Has received a live vaccination within 30 days before the first dose of study treatment or is scheduled to be administered during the study period. 18.Patients with a history of psychotropic substance abuse who are unable to abstain or who have mental disorders. 19.Participated in other clinical trials within 4 weeks. 20.The researchers believe that there are other circumstances that are not suitable for this clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-Limiting Toxicity;Overall response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression free survival;Overall survival;Disease control rate;Duration of response;Safety; | — |
Countries
China
Contacts
Public ContactYuan Zhengang
The Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital)
Outcome results
None listed