NEW YORK (GenomeWeb) – Diagnostics firm Biodesix this week presented data on a new proteomic test for determining melanoma patients who are likely good responders to Bristol-Myers Squibb's programmed death 1 (PD-1) checkpoint inhibitor nivolumab (Opdivo).
In a study looking at a total of 149 subjects with advanced unresectable melanoma, patients scoring as likely good responders showed significantly better overall survival and time to progression than patients scoring as likely poor responders.
According to Richard Hockett, Biodesix's chief medical officer, the company plans to begin offering the test for melanoma in the near term. Longer term, he told GenomeWeb, the aim is to study the test's usefulness for guiding PD-1 inhibitor therapy in lung cancer, the disease that has traditionally been Biodesix's primary area of focus.
Last month the US Food and Drug Administration approved nivolumab for treatment of patients with advanced non-small cell lung cancer who have progressed during or after platinum-based chemotherapy.
Like Veristrat, Biodesix's proteomic test for identifying patients with advanced NSCLC who are likely responders to EGFR inhibitors, the nivolumab test is based on MALDI mass spec. Hockett said, though, that the company's discovery platform has advanced since the development of Veristrat. New mass spectrometers allow for detection of more proteins, and the informatics underlying development of the classifier have grown more sophisticated, he said.
MALDI remains Biodesix's mass spec method of choice, but the company has of late begun branching out into new mass spec approaches. This summer, for instance, it announced a collaboration with Swiss proteomics firm Biognosys on companion diagnostic development, in which it will use that company's data-independent HRM mass spec technology to, among other things, better understand the specific analytes underlying its test's MALDI signatures.
The PD-1 inhibitor test, which the company presented on in a poster at this week's Society for Immunotherapy of Cancer annual meeting inNational Harbor,Maryland, uses 59 MALDI mass spec features. Biodesix has not identified the majority of the proteins underlying these features and does not plan to, Hockett said. Among the proteins comprising the test that the company has tentatively identified are c reactive protein, amyloid bA4, transthyretin, vitronectin, granulin, serum amyloid A, C3a, and A1.
Biodesix developed the test using 119 patient samples from a Phase I clinical trial (NCT01176461) sponsored by the Moffitt Cancer Center and the National Cancer Institute investigating vaccine therapy and nivolumab therapy in advanced melanoma patients. They used 60 patient samples for development of the classifier and then the remaining 59 for testing it. They then did outside validation using samples from an additional 30 patients with advanced unresectable melanoma taken from an observational study.
The study found that patients classified by the test as likely good responders had time to progression of 230 days compared to 84 days for likely poor responders. For patients classified as likely good, the other endpoint of overall survival was not reached, while for those identified as likely poor it was 61 weeks.
Biodesix is now pursuing new sample sets for additional validation of the test and plans to make it commercially available in the near future as a laboratory-developed test. The company also offers Veristrat as an LDT, although it is working to take that test through FDA 510(k) clearance as part of its ongoing agreement with drugmaker Aveo Oncology.
Under that agreement, the two parties are co-developing and commercializing Aveo's non-small cell lung cancer antibody drug ficlatuzumab and Veristrat as a companion test to predict best responders. The deal calls for Biodesix to fund the first $15 million of the drug development effort with the expenses thereafter split evenly between the two firms and profits from commercialization of the drug also split evenly.
Hockett said this week that the company would likewise take the new PD-1 test through FDA were it to find a pharma partner who wanted the test as a companion diagnostic.
He added that Biodesix is "actively trying to get [sample] sets to move this test into lung cancer. That is our ultimate goal, since we are a lung-focused company."
Hockett said there was no reason to expect the test's performance would be specific to melanoma. Rather, he said, "we fully anticipate this will have applicability in every tumor type in which PD1 checkpoint inhibitors are used."
He analogized it to Veristrat, which, he noted, was applicable to a wide variety of different tumors in which EGFR inhibitors are used. Biodesix has tested Veristat in a number of different cancers, finding utility for the test in more than a dozen, Hockett said. However, the overwhelming focus of its energy to date has been in NSCLC.
One factor that will affect when the company begins offering the new classifier for melanoma is how implementation of the Protecting Access to Medicare Act of 2014 plays out, Hockett said. The law changes how diagnostic payment rates are determined by the Centers for Medicare & Medicaid Services and, some fear, could negatively impact reimbursement for certain kinds of tests.
The law also establishes a new category of test called advanced diagnostic laboratory tests (ADLTs), which is defined as tests that use an algorithm to interpret collections of DNA, RNA, or protein markers or an FDA-approved or –cleared test.
The initial ADLT definition would exclude Veristrat and the new PD1-inhibitor test, Hockett said, adding that this result is "hotly disputed."
"We are still working through the ramifications for reimbursement, but once we understand those, we plan to bring the test out," Hockett said. "It could be months from now, because we have to make sure we understand the implications of the new laws, but our intent is to put it out for melanoma as soon as we understand those restrictions."