This is a phase II, multicenter, single arm study designed to evaluate the efficacy and safety of Inavolisib in second line pancreatic ductal adenocarcinoma（PDAC） patients.
This study will be conducted in two stages and expected to enroll up to approximately 62 patients. In the safety run in stage, approximately up to 12 patients will be enrolled to receive Inavolisib under 3+3 design. After safety run-in, if the tolerability allows, an additional 50 patients will be enrolled.（expansion stage）.
Dose Modification Guidelines for Inavolisib-Related Adverse Events: Inavolisib started at dose 9 mg QD, first reduction to 6 mg QD, second reduction to 3 mg QD. If the patient continues to experience specified drug-related adverse events after the second dose reduction, Inavolisib should be permanently discontinued.
Tumor assessments will be performed every 8 weeks, including enhanced chest CT, abdominal CT / MRI and pelvic CT / MRI.Head CT/MRI also can be performed if necessary. Additional scans will be performed as clinically indicated.
Tumor specimens acquired from biopsy will be collected for E-cadherin testing by IHC at each site. Tumor tissue (via biopsies and/or surgical resection) and blood samples from eligible patients will be provided to a local laboratory and tested and analyzed for biomarkers that might be associated with clinical benefit, tumor immunobiology, mechanisms of resistance, et al.
Patients will be closely monitored for adverse events throughout the study, including the incidence, nature and severity of adverse events and laboratory abnormalities graded per National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE 5.0).
1.Signed Informed Consent Form 2.Age ≥ 18 years at time of signing Informed Consent Form 3.Ability to comply with the study protocol, in the investigator's judgment 4.Histologically or cytologically confirmed diagnosis of pancreatic ductal adenocarcinoma.
A formalin-fixed, paraffin-embedded (FFPE) tumor specimen in approximately 8-10 slides containing unstained, freshly cut, serial sections should be submitted along with an associated pathology report within 4 weeks of randomization.
If fewer than 8 slides are obtained, but there are enough slides for E-cadherin testing by local lab of each site patients are still eligible.
ANC ≥ 1.5 × 109/L (1500/μL) without granulocyte colony-stimulating factor support
1.Prior treatment with any PI3K, AKT, or mTOR inhibitor, or any agent whose mechanism of action is to inhibit the PI3K-AKT-mTOR pathway.
Measurable disease outside the CNS
No ongoing requirement for corticosteroids as therapy for CNS metastases, with corticosteroids discontinued for ≥ 2 weeks prior to enrollment and no ongoing symptoms attributed to CNS metastases
Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic assessments