P2.12-05 SUKSES (Small Cell Lung Cancer Umbrella Korea Studies): A Phase II Biomarker-Driven Umbrella Study in Relapsed or Refractory SCLC

Abstract

Although initial platinum-based treatment demonstrated high response rate (RR) in extensive stage SCLC, limited options are available for subsequent systemic therapy. Recent studies with comprehensive genomic profiling identified cell cycle-related gene alteration, such as TP53 and RB1 inactivation, and RICTOR amp as a major characteristic of SCLC. Based on this observation, we designed umbrella clinical trial based on the hypothesis that controlling cell cycle checkpoint, DNA damage repair mechanism, and mTOR pathway with small molecules and monoclonal antibodies targeting these pathways might be an effective approach for the later line SCLC treatment. SUKSES trial (NCT02688894) is a phase 2 study with seven treatment arms. Four arms for the biomarker-positive population. Arm A (AKT1 mt); Arm B (BRCA1 or BRCA2 mt, ATM deficiency, MRE11A mt or other HR pathway gene mt); Arm C (MYC family protein amplification or CDKN2A mt either of which combined with TP53 mt); Arm D (RICTOR amp). Three arms for the biomarker-negative population. Arm-N1, N2, and N3. Pathologically confirmed SCLC patients are eligible for the molecular screening. For study participation, patients must have at least one measurable lesion after progression from first-line platinum-based therapy. Patients are enrolled in either second or third line based on their initial treatment response. Following treatment is applied after allocation: Arm-A (AZD5363); arm-B (Olaparib); arm-C (AZD1775); arm-D (AZD2014); arm-N1 (AZD1775); arm-N2 (Olaparib and AZD6738); arm-N3 (AZD2811). Primary endpoint for this study is objective RR. Duration of treatment, disease control rate at eight weeks, progression-free survival, exploratory biomarker will be evaluated as secondary endpoint. As of May 2018, 157 patients have been screened for the molecular profiling. Arm A was closed due to low discovery rate of AKT1 mutation. Of the planned 28 patients for each biomarker positive arm, 9 for arm B, 7 for arm C and 4 for arm D have enrolled. For the negative-biomarker arms, 24 out of 45 patients are recruited for arm N1 and 9 patients for Arm N3. Arm N2 is under review by Institutional Review Board. Section not applicable Section not applicable