2322TiP - SOUND: A phase II trial evaluating the efficacy of molecular profiling of circulating ± tumor tissue DNA for salvage-therapy matching in patients with advanced and refractory carcinoma

Background

The decreasing costs and turnaround time of next generation sequencing methods paired with the rapidly growing arsenal of available genome-targeted drugs have significantly raised the impact of molecular profiling (MP) for treatment selection in clinical practice. However, to date, the efficacy of MP-guided cancer therapy beyond its approved clinical indication has been modest. Tumor tissue profiling alone may not be sufficient to capture the heterogeneity of advanced tumors. Of note, circulating tumor DNA (ctDNA) has recently been shown to provide the most accurate molecular snapshot of a patient's tumor composition. We thus aimed to evaluate the utility of comprehensive MP of ctDNA for personalized, cancer-agnostic treatment matching and to investigate the efficacy of MP-matched therapy in this salvage setting.

Trial design

SOUND is a multicenter non-randomized phase II trial. Adult patients with locally advanced or metastatic carcinoma who have exhausted all evidence-based therapies and have an ECOG performance status of 0-2 are eligible. At study enrollment, a mandatory liquid biopsy for the analysis of ctDNA is obtained from all patients. A biopsy of tumor tissue DNA is optional depending on the patient’s consent. MP of ctDNA and tumor tissue DNA is performed using the FoundationOne®Liquid CDx and the FoundationOne® CDx assays, respectively. In patients with available tumor tissue not older than 3 months, immunohistochemical testing of Her2, PD-L1 and NTRK is performed. All patient cases, including the molecular reports, actionable molecular targets (AMT) and MP-guided treatment recommendations are reviewed weekly in a virtual multidisciplinary molecular tumor board. The primary study endpoint is the proportion of treated patients who have a progression free survival (PFS) ratio of ≥ 1.3 comparing the PFS on the matched therapy to the PFS of the previous therapy line. Co-secondary endpoints are the proportion of patients from whom a conclusive genomic profile can be obtained, the proportion of patients with an AMT, the number of AMTs, overall survival, and therapy response rate. To date, 91 of 200 planned patients have been enrolled.

Clinical trial identification

EUDAMED: CIV-AT-21-12-038246; NCT05032092, Release Date November 4, 2021

Editorial acknowledgement

Legal entity responsible for the study

Medical University of Graz.

Funding

Roche Austria GmbH.

Disclosure

E. Heitzer: Other, Personal and Institutional, Advisory Board, Presentations, Funding IITs: Roche Austria GmbH. A. Gerger: Other, Personal and Institutional, Advisory Board, Presentations, Funding SOUND Study: Roche Austria GmbH. All other authors have declared no conflicts of interest.