NEW YORK (GenomeWeb) – Ohio State University's Comprehensive Cancer Center has launched a precision cancer medicine clinical trial geared toward patients with advanced or metastatic disease that combines next-generation sequencing-based panels for clinical testing with research-based exome and transcriptome sequencing and novel drug trial designs.
The clinical trial was launched last November, and the laboratory has evaluated more than 75 patients, at a rate of about four to six per week, but is scaling up and expects to evaluate around 400 patients total, Sameek Roychowdhury, assistant professor in medicine, who is running the precision medicine trial at Ohio State, told GenomeWeb.
Eligible patients, both with solid and liquid tumors, who are referred to the clinic first receive testing via a pan-cancer clinically validated NGS panel. Testing also includes germline sequencing. The patient's doctor can use those results to make treatment decisions.
Patient samples are also sent through a research pipeline for exome and transcriptome sequencing. Those results are not returned to the individual patients, but the exome and transcriptome sequencing informs clinical panel development.
Finally, the group is developing clinical trials that look to stratify patients based on their mutational profile.
The primary outcome measures are to see how many patients receive a therapy based on their genomic findings, as well as to quantify the overall impact on clinical care. In addition, the researchers are evaluating metrics like the average turnaround time of the test.
The CLIA-certified cancer genomics lab runs its panels on three Illumina MiSeq instruments. The exomes and transcriptomes are run in a research setting on the Illumina HiSeq.
The pan-cancer panel targets around 250 genes with therapeutic implications. "We honed our gene panel to be focused on therapies as opposed to just the genes that are prevalent in cancer," Roychowdhury said.
In addition, he said, the lab runs a validated RNA panel focusing on 100 genes to detect gene fusions and aberrant expression levels. The genes on that panel are part of the so-called druggable kinome, he said. The group custom designed the panel using probes from Integrated DNA Technologies.
Roychowdhury said that the group is also building up a database it calls Cancer Driver Log (CanDL) of actionable driver mutations that can be targeted with a drug, are associated with increased sensitivity to a drug, or are linked to drug resistance.
Patients who consent to the trial also consent to more comprehensive genomic testing in a research setting via exome and transcriptome sequencing. Those results are not returned but are instead used to "inform our panels," he said. "For a clinical research lab that also develops clinical-grade NGS assays, we have to be mobile and ready to adapt and update our panels."
Around 40 percent of patients receive a clinically actionable finding from either the DNA or RNA panel, which Roychowdhury defines as being able to match an alteration to a therapy.
Turnaround time is seven to 10 days and testing is currently being funded through grants. That "gives us flexibility," Roychowdhury said, to not "be dependent only on genes that can be billed for." Although, he acknowledged, down the road, the laboratory would have to figure out a reimbursement strategy. Thus far, he said reception of the program has been positive, and while mostly oncologists from within the Ohio State health system are referring patients, at least 10 community oncologists have also begun to refer patients for testing.
"We communicate directly with the physicians to help them understand the report," he said. Additionally, while 40 percent of patients discover they are eligible for a drug, the majority do not, so it's "important to explain that so the expectations are clear."
For patients that are not eligible, Roychowdhury said there are other options, including clinical trials that are not mutation specific, immunotherapy approaches, and strategies that target other aspects of the cancer, like metabolism.
In addition, he said, patients often become eligible for one of Ohio State's clinical trials of targeted therapies. For instance, one trial that Ohio State is running in conjunction with the University of Michigan is a basket trial, encompassing any cancer type as long as it has a defined mutation within the FGFR pathway. The agent is a pan-FGFR inhibitor, ponatinib hydrocholoride, Roychowdhury said. The trial opened in February and so far 40 patients have enrolled.
The trial is a phase II study, he explained, evaluating patients with metastatic or refractory cancer that have mutations to FGFR, KIT, RET, ABL1, or FLT3. The trial is not specific to the tumor's site of origin, but it is designed to look for specific mutations or disease subsets that are most likely to benefit from the therapy. The goal is to determine how the study would then be expanded once the patient population — those with specific gene mutations or tumor types — is identified, he said.
Roychowdhury said that while these types of novel approaches — genomics-based trials like the Lung Master Cancer Protocol and the National Cancer Institute's Match trial — are starting to take hold, particularly now that NGS assays can be used to stratify patients, many more are needed, which would help improve cancer patients' access to potentially helpful drugs.
In addition, Roychowdhury has an eye on the future, when it is expected that NGS-based testing at Ohio State will no longer be funded through grants and will instead require patients to either pay out of pocket or insurance companies to reimburse. Clinical trials can help make the case for clinical utility, Roychowdhury said, and thus, reimbursement.
"That will help us really take care of patients," he said.