NEW YORK – An organoid-based test may be able to identify which drugs cancer patients are likely to benefit from, according to an analysis presented during the second virtual session of the American Association for Cancer Research's annual meeting.
Carla Grandori, the CEO of Seattle-based SEngine Precision Medicine, presented initial data from both a retrospective and a prospective analysis of the company's PARIS test. The test combines functional drug testing and DNA sequencing of patient-derived organoids to predict which drugs may best treat patients' tumors. Although genomic profiling is being increasingly performed to personalize treatments in cancer, testing alone doesn't always identify targetable markers.
In both retrospective and prospective analysis so far, Grandori said the PARIS test has demonstrated high concordance with patient responses and identified treatment options that wouldn't have been identified from just genomic sequencing. She added that the firm is embarking on clinical trials to further validate this approach and demonstrate its clinical utility to oncologists.
"We're launching clinical trials to confirm these initial observations and obtain evidence for the clinical utility of functional testing," Grandori said. "Our hope is to turn a new corner in cancer treatments."
The PARIS test analyzes organoids derived from patient biopsy samples and ranks how well the patient's tumor is likely to respond to a range of drugs, including chemotherapy and targeted agents, by combining high-throughput screening results with genomic sequencing and bioinformatic analyses. The test, which is CLIA certified, produces a report with these treatment rankings that can help oncologists as they consider therapeutic options for patients.
The drug ranking is based on both personalization and sensitivity, where personalization is a comparative metric based on SEngine's database of drug responses and takes genomic data into account. "We found this to be the most accurate way to rank drugs for each individual patient," Grandori said.
To validate the test clinically, the firm has so far analyzed 240 patient-derived cancer organoids, testing an average of 68 drugs per patient and uncovering, on average, seven effective drugs per patient. They further reported an 18-day average turnaround time.
Grandori noted during her talk that the test now focuses on 48 drugs, but that what the test considers is flexible and can be tailored based on the patient's cancer type and genomic features.
The PARIS test has a strong concordance with clinical biomarkers, including genomic alterations, according to Gandori. For instance, 70 percent of patients with KRAS G12-mutant organoids responded to the MEK inhibitor trametinib (Novartis' Mekinist), while 37 percent of non-mutant organoids did. At the same time, only 7 percent of KRAS G12-mutant organoids responded to the EGFR inhibitor erlotinib (Genetech's Tarceva), while 30 percent of the wild-type KRAS did.
Similarly, in the case of a 57-year-old woman with pancreatic cancer with a HER2 gene amplification, the PARIS assay indicated the HER2-inhibitor lapatinib (Novartis' Tykerb) as the top-scoring drug. But the analysis also suggested other drugs that Grandori said could not be predicted by genomics alone, such as a SRC inhibitor, an mTOR inhibitor, and an ALK inhibitor. This patient, she added, was treated with a different HER2 inhibitor, trastuzumab (Genentech's Herceptin), for more than two years.
In retrospective analysis, there was more than 90 percent concordance between PARIS test results and patients' treatment responses. Grandori and her colleagues have also begun prospective analysis, which, though ongoing, indicates about an 80 percent concordance between PARIS test results and patient responses.
In one such instance, the PARIS test was used to evaluate a peritoneal metastatic tumor from a 42-year-old colorectal cancer patient. From the list of therapeutic suggestions made by the test, this patient's oncologist chose gemcitabine, a chemotherapy drug that Grandori noted is not typically used to treat colorectal cancer. The patient experienced decreased tumor burden on gemcitabine and stable disease for several months following treatment.
Meanwhile, for a 69-year-old woman with serous ovarian cancer, PARIS testing uncovered resistance to carboplatin/pacilitaxel and doxorubicin/bevacizumab, all treatments the patient previously underwent and experienced recurrence on. The test noted sensitivity to other drugs, however, such as BET, SRC, and PI3K inhibitors.
"This finding gives us much hope that targeted treatment could be effective even in cases of chemo resistance," Grandori said.
So far, Grandori's team has applied the PARIS platform to test 29 different solid tumor types, including ovarian, colorectal, and non-small cell lung cancers, and melanoma. "This indicated that organoid-based testing could be extended to all solid tumors," she said.
SEngine is now launching clinical trials to gauge the clinical utility of the PARIS test. That, Grandori added, would further show oncologists the value of the test and convince them to adopt it in their practices.
The PARIS test has a current list price of $11,000, though Grandori noted that most of the testing performed to date has been done at a discount or no cost. She added that she expects the cost of the PARIS platform to drop and eventually be about equivalent to a DNA sequencing test.