Multi-Analyte Liquid Biopsies for Treatment Guidance in Advanced Refractory Cancers: Findings of the LIQUID IMPACT Trial

Abstract

Background LIQUID IMPACT (CTRI/2019/02/017548) is a single arm, open label, phase II/III study to evaluate the feasibility of providing therapeutic guidance in cancers based on non-invasive interrogation of circulating tumor analytes in peripheral blood (Encyclopedic Liquid Biopsy: eLB). The study enrolled patients with solid organ cancers where the disease had progressed following systemic therapy failure, where no (further) viable standard of care (SoC) therapy options were available, and where invasive biopsies to obtain tumor tissue (for molecular profiling) were contraindicated. Methods Encyclopedic Liquid Biopsy (eLB) interrogated gene alterations in cell-free tumor DNA (ctDNA), and differentially expressed genes in exosomal mRNA. eLB also evaluated Circulating Tumor Associated Cells for expression of therapeutically relevant cell-surface signaling receptors as well as the chemoresistance profile towards systemic anticancer agents. Patients who received personalized combination therapy regimens based on eLB findings were evaluated radiologically to determine response to treatment, Objective Response Rate (ORR) and Quality of Life (QoL). Results At the time of submission of this manuscript, Partial Response (PR) was observed in 14 of 43 patients evaluable per protocol (ORR = 32.6%). Majority of patients reported stable to improved QoL. Conclusion The present study demonstrated that refractory cancers have latent vulnerabilities which can be identified via non-invasive eLB to design personalized label- and organ-agnostic treatment regimens to yield meaningful treatment benefit. Trial registration Clinical Trial Registry – India, CTRI/2019/02/017548 [Registered on: 02/08/2019] - http://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=31265&EncHid=&modid=&compid=%27,%2731265det%27; Trial Registered Prospectively.