Travera Clinical Study Summary

TRV-001
30 patients enrolled

This study has been designed to assess mass response as a predictive biomarker for therapy and estimate its accuracy of prediction for the mass response biomarker in 100 patients with relapsed refractory multiple myeloma (RRMM). A cohort of 100 patients was selected because it is a large enough cohort to estimate mass response’s accuracy of prediction for drug sensitivity or drug resistance independently, guiding the design of downstream clinical trials, product use, and application in drug development. In order to enable the primary objective, this study was designed with two patient cohorts. First, to define preanalytical variables affecting site-to-site sample quality, drug concentrations used for testing, and end-to-end pipeline robustness, a small Vanguard cohort of up to 30 patients with treatment naïve disease was run. This cohort is now completed, with 28 samples collected and 20 of these patients enrolled. The second, RRMM cohort is of 100 patients, with 14 samples collected and 10 patients enrolled thus far. This non-interventional study cannot be used to guide clinical decision-making or make changes to patient care, and Travera is blinding to outcomes data for the patients, except at scheduled unblinded events.

In both cohorts, bone marrow (BM) aspirate samples are collected from patients prior to the start of a new treatment regimen, and in the RRMM cohort, prospective measurements of mass response to ex vivo treatment with that same regimen are taken. Clinical data is collected in parallel to estimate the biomarker’s predictive properties (accuracy, sensitivity, specificity), and to support the improvement of the MAR biomarker through additional research and discovery within the study dataset. This data includes a clinician-determined best overall response, objective measures of response (e.g. serum protein electrophoresis (SPEP)), failure-free survival outcomes, and various other outcomes measures.

 

Clinical Study Investigators and Sites

  • Dr. Nikhil Munshi and Dr. Adam Sperling, Dana-Farber Cancer Institute

  • Dr. Andrew Branagan, Massachusetts General Hospital

  • Dr. Cara Rosenbaum and Dr. Ruben Niesvizky, Weill Cornell Medicine

  • Dr. Sundar Jagannath, Mount Sinai

  • Dr. Amrita Krishnan, City of Hope

  • Dr. Ajay Nooka, Emory Winship Cancer Institute

Solid Tumor Clinical Study:
113 patients enrolled

This collaborative research study, a sub-study of the existing “CT-Biome” Precision Biopsy Project protocol of the collaborator Anobel Tamrazi, has been designed to assess the feasibility of using MAR as a predictive biomarker for therapy in 150 patients using samples associated with their solid tumors.

The sample types include fine needle aspirates (FNAs), CORE biopsies, pleural effusions and blood. This study does not guide clinical decision-making or influence patient care in any way, but CLIA reports for samples run through approved CLIA pipelines will be returned to Dr. Tamrazi. Mass response of isolated tumor cells is tested for sensitivity to potential treatments recommended by the patients care team or Dr. Tamrazi, or in the absence of recommendations, Travera’s standard CLIA panel is run. So far, 77 of 150 patients have been enrolled in this study. From that patient population, 25 FNAs, 3 CORE biopsies, 22 pleural effusions, 13 Ascites, and 21 Biopsies have been received, with some patients providing tissues from multiple modalities. These samples have been used for extensive protocol development, both for sample handling, processing, and new test develop (e.g. checkpoint inhibitors).

Dr. Tamrazi annotates relevant patient clinical information after a reasonable period has elapsed post-enrollment, including a range of de-identified data (e.g. redacted pathology reports, demographic information, treatment history, response to therapy, genetic and epigenetic characterization, etc.). When possible, clinical outcomes have been matched to measured outcomes. Thus far, 17 total samples have been matched to outcomes, with an accuracy of 80%.

 

Clinical Study Investigator and Site

  • Dr. Anobel Tamrazi, Sequoia Hospital, Dignity Health

AML Clinical Study:
24 patients enrolled

This collaborative pilot research study with Dr. Marlise Luskin and co-investigators from the Dana-Farber Cancer Institute (DFCI) Acute Leukemia Group is focused on testing the potential utility of mass response as a biomarker in acute myelogenous leukemia (AML). In total, 30 AML patient samples will be obtained from peripheral blood draws or bone marrow aspirates at DFCI and provided to Travera.

Currently, the focus of this study includes patients going onto treatment with hypomethylating agents (HMA)+Venetoclax, FLT-3 inhibitors (e.g. gilteritinib), or 7+3 therapy (e.g. cytarabine + daunorubicin), however, enrollment criteria are not constrained.

Development with these samples has focused on pre-analytical variables as well as matching outcomes. Focus on clinical parameters related to sample collection has defined the lower limits of circulating disease required for useable samples. For defining shipping conditions, samples are couriered same-day to Travera, and can be kept overnight at 4˚C as a proxy. Processing parameters such as the surface marker used for tumor cell enrichment have also been explored.

Dr. Luskin is responsible for annotating patient outcomes on a regular basis post-enrollment. In total, 24 samples have been procured, and 16 have been annotated for response outcomes with an accuracy of 80%.

 

Clinical Study Investigator and Site

  • Dr. Marlise Luskin, Dana-Farber Cancer Institute

TRV-002
Enrollment not started yet

The primary objective of this 130-patient pilot study is to validate whether the mass response biomarker has the potential to predict the response of patients to specific therapies or therapeutic combinations using isolated tumor cells from varying cancers and biopsy formats. In this study, samples will be collected from patient cohorts of patients with breast cancer (30 pts), lung cancer (30pts), multiple myeloma (20 pts), acute myelogenous leukemia (20pts), and any patient with a carcinoma-associated malignant fluid (30pts). For each cohort, the number of patients per cohort was selected in order to fairly assess pre-analytical variables affecting the measurements (e.g. constraints due to sampling format or processing) and screen a sufficient number of patients to draw preliminary conclusions regarding mass response predictive accuracy by correlation to clinical outcomes. This study is not created to guide clinical decision-making, although data can be returned to the patient’s physician if the data is produced within Travera’s CLIA lab and license and according to an approved CLIA test’s associated standard operating procedures (SOPs).

Samples are collected by disease-specific SOC procedures for patients undergoing routine biopsy of their tumor as part of their clinical care (e.g. for clinical diagnosis, staging, DNA molecular analysis, cytology), with sample types including blood samples, bone marrow aspirates, core and/or fine needle aspirate (FNA) biopsies, or paracentesis/Pleurex catheter drainage. Tumor cells and immune cells isolated from these sources are then prospectively tested for sensitivity or resistance to therapies the patient is planned or likely to receive. In general, the first 5 samples in each cohort of this study will be used both for biopsy format-specific validation of previously established standard operating protocols (SOPs; e.g. shipping, processing) and for contributing to assessing the potential of the biomarker to predict patient outcomes. The remaining samples of each cohort will be used in addition to contributing to assessing the potential of the biomarker to predict patient outcomes. Following Travera’s receipt, samples will be processed using existing protocols for each combination of cancer and biopsy type to ensure that these SOPs regularly produce measurable cells in sufficient numbers for screening drugs. If changes are necessary to improve yields, those changes will be made within the first 5 patients and subsequently all samples will be handled according to these locked SOPs.

Clinical data regarding patient outcomes and orthogonal data will be collected after a minimum of 2 months has elapsed from the time of patient treatment initiation (or best overall response (BOR) or failure-free survival (FFS) has been met). This information will include a range of de-identified data (e.g. portions of redacted pathology reports, limited demographic information, relevant treatment history, response to therapy, and relevant genetic and epigenetic characterization). This clinical data will be sent to Travera for correlation to the mass response.

 

Clinical Study Investigator and Site

  • Dr. Andrew Pippas, John B. Amos Cancer Center

TRV-003 (TraveraRTGx)
Enrollment not started yet

The goal of this 200-patient pilot study, in partnership with xCures and their longitudinal observational research study XCELSIOR (NCT03793088), is to validate whether the mass response biomarker has the potential to predict the response of patients to specific therapies or therapeutic combinations using isolated tumor cells from malignant fluids such as pleural effusions and ascites for a patient presenting with any carcinoma. This study will utilize samples from patients undergoing routine draining of malignant fluids for diagnostic or palliative standards of care (SOC). The number of patients was selected in order to screen a sufficient number of patients to draw conclusions regarding mass response’s predictive accuracy by correlation to clinical outcomes for both small molecule therapies such as chemotherapies and TKIs, and for immunotherapies. While the study is not designed or intended to influence patient care, reports will be shared with xCures as the study site for their use via Travera’s CLIA lab reporting system. These reports will then be shared with providers and patients through the xCURES patient portal.

All samples will be collected during SOC malignant fluid drainage for palliative care or scheduled paracentesis that is prospective to the patient’s next line of treatment. The sample will be shipped to Travera according to established SOPs and using CLIA product materials. Following receipt from Travera, the samples will be processed using existing CLIA protocols for sample accessioning, quality assurance, tumor cell isolation, in vitro drug dosing, measurement, and reporting as described in Section 3.4. The drugs that are tested in vitro will be based on the guidance of the study site, and/or drawn from Travera’s standard therapy testing panel for that malignancy. These measurements will be used to evaluate the ability of the measurement platform to observe meaningful mass response by correlation to expected and measured patient outcomes.  

Clinical outcomes data will be captured according to patient co-enrollment XCELSIOR. Patients will consent to XCELSIOR and permit access to their electronic medical records to the research team at xCures, Inc. xCures manages all records collection and data entry for the study centrally. Treating physicians or their staff are not required to enter data but are asked to assist xCures in gathering records generated in the standard care of their patients.

 

Clinical Study Investigator and Site

  • Dr. Jennifer Grandis (UCSF), xCures Decentralized Oncology Study Sites