Advanced solid tumor
Conditions
Interventions
Experimental group :Phase Ib(Safety run-in,N=6):Linperlisib:80mg QD oral in a 21or28-day cycle. Second-line standard of care is based on clinical practice.
Phase II(Expansion phase, N=125): Linpe
Sponsors
The First Affiliated Hospital,Zhejiang University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1.Ages 18-80, gender unlimited. 2.Pathologically confirmed advanced solid tumor, at least one measurable lesion (according to RECIST v1.1 requirements), the tumor species selection of subjects in different cohorts in Phase II expansion phase is as follows:Cohort 1: colorectal cancer;Cohort 2: Gastric cancer;Cohort 3: Pancreatic cancer;Cohort 4: Breast cancer;Cohort 5: driver-negative non-small cell lung cancer; 3.Patients with disease progression or toxicity intolerance after first-line systemic therapy. 4.ECOG score of 0-1. 5.Expected life expectancy is more than 3 months. 6.Adequate organ function: ANC=1.5×109/L;PLT=90×109/L;Hb=90 g/L;TBIL=1.5×Upper limit of normal value (ULN); ALT AST=2.5×ULN ; SCr=1.5×ULN or CCr = 50 mL/min ;APTT=1.5×ULN;LVEF=50%;QTcF <450 ms(male), QTcF <470 ms(female), QTc interval is calculated using the Fridericia formula. 7. Previous anti-tumor treatments, including chemotherapy, radiotherapy, steroids, targeted drugs, or biologic immunotherapy, have a washout period of = 4 weeks or 5 half lives from the end of the first use of the investigational drug (including washout periods of = 2 weeks for oral fluorouracil and small molecule targeted drugs, and = 6 weeks for mitomycin C and nitrosylurea). 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.Patients with other ongoing malignancies or other malignancies that require aggressive treatment. 3.Patients with untreated or symptomatic brain metastases. 4.Having active autoimmune disease in the past 3 months, requiring systemic treatment, or having a serious history of autoimmune diseases, or requiring systemic steroids or immunosuppressants syndrome. 5.Patients with active viral, bacterial or fungal infection that requires treatment (such as pneumonia, etc.). 6.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. 7.Patients received target lesion radiotherapy within 4 weeks prior to the first dose of study therapy. 8.Hepatic encephalopathy , hepatorenal syndrome, Child-Pugh score of B or more severe cirrhosis. 9.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. 10.Pregnant or lactating women, or a pregnancy test with a positive result . 11.Medical history of immunodeficiency syndrome (AIDS)-defining illness, including Human immunodeficiency virus (HIV) infection, or allogeneic bone marrow/stem cells transplant or organ transplant. 12.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. 13.In the past 5 years, patients have had other malignant tumors that have not been cured, but not including malignant tumors that have been clearly cured or curable cancers such as basal cell carcinoma or squamous cell carcinoma of the skin, papillary thyroid carcinoma, cervical carcinoma in situ, or breast carcinoma in situ; 14.Individuals with HBV, HCV infection (defined as HbsAg and/or HbcAb positive and HBV-DNA copy number = 1 × 104 copy number/ml or = 2000 IU/ml) or acute or chronic active hepatitis C. 15.Has received a live vaccination within 30 days before the first dose of study treatment. 16.Patients with a history of psychotropic substance abuse who are unable to abstain or who have mental disorders. 17.Participated in other clinical trials within 4 weeks. 18.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,DLT;Overall response rate,ORR; | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression-free survival, PFS;Overall survival ,OS;Disease control rate ,DCR;Duration of remission,DOR;Safety; | — |
Countries
China
Contacts
Public ContactRuan Jian
The First Affiliated Hospital,Zhejiang University School of Medicine
Outcome results
None listed