Encyclopedic tumor analysis for guiding treatment of advanced, broadly refractory cancers: results from the RESILIENT trial

Abstract

RESILIENT (CTRI/2018/02/011808) was a single arm, open label, phase II/III study to test if label agnostic therapy regimens guided by Encyclopedic Tumor Analysis (ETA) can offer meaningful clinical benefit for patients with relapsed refractory metastatic (r/r-m) malignancies. Patients with advanced refractory solid organ malignancies where disease had progressed following ≥2 lines of systemic treatments were enrolled in the trial. Patients received personalized treatment recommendations based on integrational comprehensive analysis of freshly biopsied tumor tissue and blood. The primary end points were Objective Response Rate (ORR), Progression Free Survival (PFS) and Quality of Life (QoL). Objective Response (Complete Response + Partial Response) was observed in 54 of 126 patients evaluable per protocol (ORR = 42.9%; 95% CI: 34.3%–51.4%, p < 0.0001). At study completion, Disease Control (Complete Response + Partial Response + Stable Disease) was observed in 114 out of 126 patients evaluable per protocol (CBR = 90.5%; 95% CI: 83.9% - 95.0%, p < 0.00001) and Disease Progression in 12 patients. Median duration of follow-up was 138 days (range 31 to 379). Median PFS at study termination was 134 days (range 31 to 379). PFS rate at 90 days and 180 days were 93.9% and 82.5% respectively. The study demonstrated that tumors have latent vulnerabilities that can be identified via integrational multi-analyte investigations such as ETA. This approach identified viable treatment options that could yield meaningful clinical benefit in this cohort of patients with advanced refractory cancers.

Liquid biopsy and multi-analyte testing guided treatment of HER2 positive periampullary adenocarcinoma with durable complete response after trastuzumab based therapy

“…Identification of HER-2 amplification led to an opportunity to use trastuzumab based combination therapy that resulted in excellent response. This label-/organ-agnostic treatment approach helped to achieve better clinical outcome in the present case as described previously [16,32]. HER2 amplification represents potential molecular target for treatment in the subset of HER-2 amplified periampullary carcinomas.…”

“…Here, we report a case of distal CBD subtype of periampullary carcinoma who has had excellent durable response after HER2 targeted therapy in combination with chemotherapy designed based on Encyclopedic Tumor Analysis (ETA) (Exacta ® ) [16]. Encyclopedic Tumor Analysis (ETA) (Exacta ® ) offers integrative multi-analyte investigations of the tumor which captures in depth information about the multi-layered tumor interactome.…”

Clinical utility of circulating tumor-associated cells to predict and monitor chemo-response in solid tumors

“…The present manuscript reports findings of exploratory investigations from three prospective interventional trials and one prospective observational trial. The interventional trials are: (a) "The assessment of potential benefits of molecular analysis and in vitro chemo response directed at opening treatment options for relapsed and refractory metastatic solid organ tumors.-RESILIeNT" [13] This manuscript does not report the primary study outcomes or the primary efficacy endpoints for any of the above trials. Study outcomes for the RESILIENT Trial have already been published [13], while those for ACTPrO, LIQUID-IMPACT and TrueBlood trials will be published separately.…”

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

“…Pro ling of mutations in ctDNA was performed as described previously 1 . Gene expression pro ling of exosomal mRNA was performed as described previously 1 .…”

“…Patient-speci c therapy recommendations (TR) were generated as described previously 1 and provided to the treating clinicians (TC) within 7 to 10 days of receipt of patients' blood samples. Individual TRs were evaluated by the TC, who also reviewed tness of each patient based on the clinical history of prior treatments and known therapy related adverse events (AEs).…”