Entrectinib Clinical Trials: Changing the Game with Genetic Testing

STARTRK-2 trial is a currently enrolling trial to test the efficacy and safety of the agent entrectinib which targets 5 abnormalities across a number of cancer sites. 
BY Allie Casey
PUBLISHED February 15, 2017
For Corey Wood, a 25-year-old patient with lung cancer, genetic testing was a “game changer.” Finding out that her tumor was ROS1-positive was the beginning of the path to the rest of her life.

She’s been on entrectinib, an investigational therapy that inhibits certain mutations, leading to tumor shrinkage, for almost two years now. In that time, she’s moved from California to Denver, Colorado, started working full time and is enjoying a more normal life.
 
"I don’t know where I would be if I wasn’t on targeted therapies,” she said, in an interview with CURE®, arranged by the Bonnie J. Addario Lung Cancer Foundation.

It was reading online forums that introduced Wood to the idea of mutations and targeted therapy — reading about this “miracle therapy.” She went to her oncologist asking about genetic testing, only to find that he had already sent her needle biopsy out to be tested. The results, however, showed that her tumor had tested negative for EGFR, ALK and KRAS, some of the more popular abnormalities.

Her oncologist didn’t give up there. He wanted to test again, and further, for more mutations. Wood said, “All I heard was, ‘You have a chance.’” It required another surgery to get a larger sample and, a few weeks later, the results were in. Wood was ROS1-positive.

“If he [her oncologist] hadn’t said, ‘Maybe we should do another test,’ I don’t think I would have pushed for it, or looked,” Wood said. For many patients, getting that testing is the first step. Pratik Multani, M.D., called it, “the entry into these potential opportunities.”

Multani is the chief medical officer of Ignyta, the company that manufactures entrectinib. Currently, Ignyta is running a phase 2, open label clinical trial of the therapy. The intent of this study, as Multani put it in an interview with CURE®, is “to gather patient efficacy and safety information in the appropriate patient population, with the targets of interest, across any tumor type.”

Rather than treat a specific cancer site, entrectinib treats a series of gene mutations: ALK, ROS1, NTRK1/2/3. Inhibiting these abnormalities, as entrectinib does, can lead to shrinkage of the cancer.

The presence of one of the five abnormalities is “relatively uncommon, in the single-digit percentage range,” explained Multani. However, they can be found in a variety of tumor types: non-small cell lung cancer, colorectal cancer, head and neck cancer, salivary gland cancer, sarcomas and melanoma, to name a few. If a patient’s tumor tests positive for any one of these targets, “there’s the potential that entrectinib could inhibit that patient’s tumor.” It also means that the patient is eligible to enroll in the second of the Studies of Tumor Alterations Responsive to Targeting Receptor Kinases (STARTRK-2) trials, as long as they have never been treated with other targeted therapies for those mutations.

STARTRK-2 is a global trial that has been enrolling patients for about a year. “It’s open in 14 countries with over 100 clinical sites around the world, and 50 or more of those are in the United States,” Multani explained.

In past trials, Multani said, “79 percent [of patients] had tumor shrinkage that met standard criteria for what we call a response.” There was also evidence of long-standing response with some patients having improvements that last up to two years, or more. “That’s early encouraging data in terms of finding a dose that’s compatible with long-term dosing, acceptable in terms of side effects,” said Multani.

“A big part of the study is getting the patients’ tumors tested for the presence or absence of these targets,” Multani added.

In addition to manufacturing entrectinib and running the STARTRK trials, Ignyta also develops a diagnostic test – a “rare example where the drug and test are being developed under the same roof,” as Multani said. Ignyta’s diagnostic testing comes at no cost to patients who are part of the clinical trial.

Ignyta is not the only company that offers molecular testing to patients: Companies such as Caris Life Sciences and Foundation Medicine offer testing, too. The latter is where Wood did her testing.

From her experience, Wood considers genetic testing “extremely important.”
 
Multani pointed out the benefits of genetic testing in this capacity. “If you have one of these targets, there may be additional treatment options beyond what is the standard of care,” he said. “Those treatment options may be approved drugs, or they may be clinical trials.” Multani hopes that the STARTRK trials will help with education and expand knowledge about these tests. “It’s worth testing very broadly,” he noted.

Wood agrees. In her mind, there’s no reason not to get this kind of testing done. “Even if I had tested negative, I think I would have hung onto the idea,” she said. They don’t know my mutation now, but maybe they will.”
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