Tumor-agnostic precision immuno-oncology and somatic targeting rationale for you (TAPISTRY): A novel platform umbrella trial.

TPS3154 Background: Actionable genomic alterations are found in many solid tumors in pediatric and adult populations. Identifying such alterations can match patients (pts) to genome-driven therapies. Although TRK and immune checkpoint inhibitor therapies have tumor-agnostic approval for NTRK-rearranged and tumor mutational burden (TMB)-high cancers, respectively, similar approvals remain an unmet need for other genome-driven cancers, limiting pt access to potentially active therapies. Platform master protocol studies leveraging comprehensive next-generation sequencing (NGS) are a pragmatic means of evaluating multiple genome-driven therapies in rare biomarker-selected populations. Contemporary study designs include adult and pediatric pts to expand care across age groups. Methods: TAPISTRY (NCT04589845) is a phase 2, global, open-label, multi-cohort study evaluating the efficacy and safety of targeted therapy or immunotherapy, as single agents or in combination, in pts with unresectable, locally advanced/metastatic solid tumors. Eligible pts have tumors that harbor genomic alterations or are TMB-high by NGS (Foundation Medicine or CLIA/equivalent-certified laboratory). General inclusion criteria: PD on prior treatment/no available acceptable treatment; measurable disease (by RECIST v1.1, RANO, INRC), adequate ECOG/equivalent PS and end organ function. Pts will be assigned to treatment according to eligibility criteria for biomarker-defined cohorts (Table). Pediatric pts may be enrolled if age-appropriate formulations/dosages are established. Samples will be taken for central NGS biomarker testing at baseline (tissue/blood), tumor assessments (blood) and at response/PD (optional tissue/blood). Tumor assessments (CT, MRI, PET) will be completed at baseline then every 6–8 weeks, depending on cohort. Primary endpoint: confirmed ORR by independent review committee (IRC; RECIST v1.1). Key secondary endpoints: ORR (by investigator [INV], per RECIST/INRC); DoR, CBR, PFS, time to CNS PD (by IRC and INV, per RECIST/INRC); intracranial efficacy (Cohorts A–D; per RANO [primary brain tumors]/RECIST [baseline CNS mets]); OS; patient-reported outcomes; safety; pharmacokinetics and immunogenicity (Cohorts D and F). Treatment will continue until PD, loss of clinical benefit, unacceptable toxicity, discontinuation or death. Target enrollment is 650 pts at 100+ sites based on screening 40,000+ pts; 3 pts enrolled as of 9 Feb 2021. Clinical trial information: NCT04589845. [Table: see text]