Notable’s The ANSWer Study: An Observational Clinical Trial for Patients with Blood Cancer
by Susanna Wen MsM (Master of Medicine), Ph.D
Notable’s first self-sponsored clinical trial to validate cancer patient matching on its automated high-throughput scientific technology platform
At Notable, we are aiming to redefine cancer treatment with the development of a functional precision medicine platform to rapidly advance drug development. Although there are some success stories for precision medicine, overall this has been a challenging area in oncology, not to mention a point of frustration for patients searching for the right treatment for their disease. Blood cancers in particular are highly variable, not even accounting for the diversity of the patients it affects. This presents a challenge for a genomics-based precision medicine approach that attempts to match patients to treatments based on the genetic abnormalities identified in their cancer. Notable’s functional drug sensitivity assay is meant to complement genetic screening in the search to find the right drug for the right patients with blood cancer. It is our hope that our platform will one day change the way physicians make treatment decisions for patients, and more importantly, help select the right patients for the right clinical trials, ultimately speeding drug development, decreasing costs, and leading to approval of drugs that benefit specific patients– true precision oncology. To continue our efforts to validate the predictive power of our platform, the Notable team launched its first large-scale sponsored clinical trial, The ANSWer study, at the end of last year.
Notable’s assay platform enables the testing a large number of monotherapies or drug combinations in fresh patient samples, with an automated, high-throughput, flow cytometry- based readout. The readout incorporates diverse measurements including apoptosis, proliferation, differentiation, and “stemness,” as well as expression of immunotherapy targets. Individualized assay conditions create microenvironments designed to accurately reflect a specific disease, along with the ability to further tune these microenvironments for each specific drug class being tested. Samples collected from patients who receive standard of care therapies are tested against those same agents in Notable’s ex vivo drug sensitivity assay, the results of which will then be compared to the patient’s clinical response. Assay results are analyzed with, and compared to, prospectively collected clinical results, and retrospective clinical data (samples with known clinical outcomes, correlations with genomic signatures, and correlation with clinical trial results). An initial proof-of-concept study collaboration with Dr. Peter Greenberg at Stanford University comparing clinical outcome of patients with results of Notable’s ex vivo drug sensitivity assay demonstrated a positive predictive value (PPV) of 92% and negative predictive value (NPV) of 82% in patients diagnosed with myelodysplastic syndrome (MDS).
The results of this proof-of-concept study are incredibly exciting and provide a glimpse at the potential and power of the Notable assay to help get the right drug to the right patients. In order to continue building this predictive power and improve the accuracy of our functional assay, the Notable team designed a prospective, multi-center observational study to collect de-identified biospecimens with matched clinical data from up to 1,000 participants from clinical networks in the United States and Canada. Relevant de-identified clinical information and medical data will be collected from participants upon study entry and during subsequent visits for up to one year. Hematologic malignancies that will be studied in this trial include: Acute Myeloid Leukemia, Multiple Myeloma, Myelodysplastic Syndromes, Lymphoma, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia and Myeloproliferative Neoplasm, to name a few. Samples collected from patients who receive standard of care therapies will be tested against those same agents in Notable’s ex vivo drug sensitivity assay, the results of which will then be compared to the patient’s clinical response, generating a validation dataset for the platform.
This observational trial will give Notable the opportunity to test more patients and samples than ever before, allowing us to continually increase the platform’s predictive value and eventually lead to an interventional study utilizing the assay to determine the therapy a patient receives.
The ANSWer Study is currently enrolling at 8 sites spread across the US:
More trial details are currently listed here: https://clinicaltrials.gov/ct2/show/NCT04014764
Notable’s platform improves with every patient and The ANSWer Study brings Notable’s technology one step closer to being used as a tool to help physicians and patients make complex treatment decisions in the clinic.