Abstract CT161: Clinical study of PD-1 inhibitor with mTOR inhibitor for relapsed and refractory brain tumors
Authors: zhihua Chen, Yongming Qiu
Journal: Cancer Research (2018)

Abstract In this phase I/II study the combination regimen is used to treat recurrent or refractory malignant glioma patients. The inclusion criteria: 1) Histologically confirmed WHO IV. Participants will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of glioblastoma. 2) Patients must be at first or second relapse following initial radiation-chemotherapy therapy. 3) Must provide tumor tissue. 4) Molecular diagnosis includes the mutation of PIK3CA, KRAS, TSC1 and PTEN expression decreased, meet the above 2 and above. High expression of PD-L1 in tumor and tumor infiltrating lymphocytes consider as drug specifically targeting T-cell checkpoint pathways. 5) KPS&amp;gt;/= 60. 6) Measurable contrast-enhancing tumor consists of a miaxmal volume of 3*3 cm. 7) Stable doses of steroids for 5 days, no more than 2 mg dexamethasone total per day. 8) Absolute neutrophil count (ANC) &amp;gt;/=1,500 /mcL; platelets &amp;gt;/=100,000/mcL; hemoglobin &amp;gt;/= 9 g/dL; serum creatinine /= 60 mL/min for subject with creatinine levels &amp;gt; 1.5 × institutional ULN. 9) Both sexual and age &amp;gt;/= 18 years on day of signing informed consent, 5 to 18 years of age signing informed consent by parents. Exclusion criteria: 1) Treated previously with bevacizumab. 2) Has tumor localized primarily to the brainstem or spinal cord. 3) Has received prior interstitial brachytherapy, implanted chemotherapy, or CAR-T cell therapy. 4) Currently participating in or has participated in a study of an investigational agent or using an investigational device 4 weeks since last dose of agent administration. 5) Has a diagnosis of immunodeficiency or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial. 6) Has evidence of interstitial lung disease or active, non-infectious pneumonitis. 7) Has an active infection requiring systemic therapy. 8) Pregnant or breastfeeding. 9) Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 antibody. 10) History of HIV, HBV, HCV. 11) Has received a live vaccine within 30 days prior to the first dose of trial treatment. According to the results of tumor molecular evaluation, patients would be divided into three intervention groups. The interventions are EVE group (Everolimus 10mg PO QD), PD-1 inhibitor monotherapy group (PD-1 inhibitor 2mg/kg ivgtt Q3W) and combination group (Everolimus 10mg PO QD + PD-1 inhibitor 2mg/kg ivgtt Q3W). Primary outcome measure: 6 month progression-free survival rate, progression will be determined by review of MRI exams every month, assessed using iRANO criteria. Secondary outcome measures: 1) Overall survival (OS) and progression-free survival (PFS). 2) Incidence of grade 3+ toxicities. 3) Helper and effecter T cells active percent, T reg and MDSC percent in peripheral blood will be detected before and after treatment Day 1, 3, 7 and 3 weeks in every cycle. This clinical trial has supported by IRB of Renji hospital and registered on ICTRP identifier: ChiCTR-OON-16008330. Citation Format: zhihua Chen, Yongming Qiu. Clinical study of PD-1 inhibitor with mTOR inhibitor for relapsed and refractory brain tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT161.