NEW YORK – In a model that it hopes will help clinicians better realize the promise of precision medicine, cancer sequencing firm Caris Life Sciences took a major step last month to create a combined genetic testing and clinical trial matching service by acquiring trial site management firm Pharmatech.
Although Caris has been working with Pharmatech for several years, the acquisition is necessary to achieve the firm's goal, which is to change the paradigm of clinical trials matching on a large scale, said Caris President and Chief Scientific Officer David Spetzler. Merging the two companies also aligns incentives. "Without [that] … you've got us negotiating with them and they're negotiating with various pharma companies, and potentially other labs, and it just gets much messier for us to change the paradigm," he said.
As the practice of precision oncology has begun to mature, so has the field's recognition of the barriers to making good on its promises. One obstacle that has emerged is the challenge of turning an actionable finding — mutations that mark patients as eligible for new classes of effective therapies — into a resulting action.
Clinical trials using next-generation sequencing to mine broad swaths of the genome continue to show that significant numbers of patients across varieties of cancer types do have targetable or actionable mutations. But so far, relatively small proportions of those who test positive for a target actually end up getting the matched drug, especially in the context of rare alterations and emerging, experimental therapies. Often by the time doctors and researchers are able to acquire the drug, patients pass away.
Caris has not been alone in looking to a model that tries to address the practical challenges of getting patients onto molecularly guided treatments . Strata Oncology, for example, has built its genomic medicine business around a model in which it forges partnerships with healthcare systems and offers free testing to advanced cancer patients within what it calls its "Precision Oncology Network." The company then charges pharmaceutical companies for access to that data, which they can use to identify patients suitable for enrollment into their clinical trials.
But Caris President and Chief Scientific Officer David Spetzler said that the paradigm the company hopes to create with its acquisition of PharmaTech will hopefully bring the field closer to demonstrating that molecularly directed treatment can truly and significantly improve patient outcomes.
"We're trying to change the order of things," Spetzler said in an interview. "Generally, what would happen is a physician would order molecular testing, and then that physician would be required to reach out to various places to try and find if there was a trial that the patient would be eligible for. … I think that's one of the reasons why we see such a very small percentage of patients actually getting on trials in this country, and so what we are hoping to do is to change that model dramatically."
The new generation of targeted treatments are going to be indicated for smaller and smaller subsets of patients. NTRK fusions, which are targeted by TRK inhibitors like larotrectinib (Vitrakvi), for example, occur in less than 1 percent of solid tumors. The rarity of these markers in the population is a big challenge for clinical trial matching.
In order to identify patients with rare biomarkers, more patients need to have their tumors profiled, there need to be studies investigating drugs targeting those markers, and there needs to be a system for quickly identifying the patients for these trials and getting them the drug. "That's what's so exciting, is that we have the scale in terms of the number of patients that we're profiling, and Pharmatech has scale in terms of the number of sites that are already contracted to be able to bring these trials," he said.
Pharmatech markets a methodology that it calls "just in time", which re-organizes the logic of clinical trial matching. Instead of oncologists hunting for a clinical trial for which they can match patients, Pharmatech creates a web of participating research institutions and oncology practices that pre-identify patients based on a variety of eligibility criteria upfront — before ever being activated as a trial site. According to the company, this means that when a patient presents with trial-eligible alteration at one of its participating practices — even if that institution is not yet approved as a trial site — the company can get that site activated and the patient on the trial protocol within 10 days.
In studying this approach, Pharmatech has been able to demonstrate that this strategy reduces the time it takes from when a doctor discovers a patient who could benefit from a trial to when that patient can enter treatment. For instance, a study focused on pancreatic cancer found that sites using the just-in-time model accrued subjects at more than twice the rate of traditionally activated sites.
"They've actually been doing this since the 80s," Spetzler said. "They've been most successful in really compressing the amount of time from patient identification to getting them on the trial, and this timing is everything for these patients."
Recent research suggests that the time between molecular profiling and getting on treatment impacts patient outcomes. In the I-PREDICT study, for example, researchers were able to identify personalized therapies and get 49 percent of patients on those drugs. They also calculated what they called "matching scores," showing that a high score predicted both better progression-free and overall survival.
In I-PREDICT, which has one of the highest match rates seen in precision oncology trials, the median time between study consent and treatment initiation was one month. In a Nature Medicine paper, the authors led by Razelle Kurzrock from the University of California, San Diego, wrote that one of the reasons they were able to achieve a high match rate is because patients were tested for a large panel of targetable markers by a next-generation sequencing panel, and a molecular tumor board had discussions immediately upon receiving the test results to ensure patients could get on treatment without delay.
Justin Stebbing, a professor of cancer medicine and medical oncology at Imperial College London, has also led research showing the challenge of getting patients on treatments to which they're molecularly matched. He said in an email that the potential solution as defined by Caris with its Pharmatech acquisition make sense to him.
Stebbing and colleagues were involved in a study published last year in the journal Oncotarget in which they evaluated the effect of tailoring treatments based on predictions informed by Caris' molecular profiling service, concluding that patients whose treatments matched those predicted to be of benefit had improved survival over those who did not. But in that study, as in others, at least as many patients with actionable mutations failed to receive a matched treatment as those who received one.
Considering what Caris is pursuing in aligning its operations with Pharmatech's, Stebbing agreed that it could be a way to "change the paradigm of how molecularly based clinical trials are performed."
"Instead of doctors having to know about all the trials and markers and patients having to travel to sites where the trials are open, we can identify the patients that are eligible and then bring the trial to that doctor and patient," he wrote.
"Pharmatech has been doing this for years, but without the molecular data, " he added. In combining the two, "we (doctors/patients/the healthcare system) should be able to dramatically increase the number of patients that get on trials."