ASCO: Shrinking 60% of lung cancers, Blueprint's RET drug poised for 2020 filing

Chicago
Blueprint Medicines presented data for its RET inhibitor BLU-667 at the annual meeting of the American Society of Clinical Oncology in Chicago. (Pixabay)

CHICAGO—Blueprint Medicines’ RET inhibitor BLU-667 shrank tumors in 60% of a difficult-to-treat group of lung cancer patients, teeing it up for a 2020 filing in patients with RET-altered non-small cell lung cancer (NSCLC) who had already tried chemotherapy.

The phase 2 data, presented Monday at the annual meeting of the American Society of Clinical Oncology (ASCO), show a “dramatically better” response than is seen with current treatments, Blueprint Chief Medical Officer Andy Boral, M.D., told FierceBiotech.

Unlike patients with other mutations such as ALK, RAS or EGFR, patients with RET mutations haven’t benefited from a targeted treatment. Instead, they routinely receive platinum chemotherapy along with "any number of drugs,” Boral said. If a patient’s disease gets worse, there aren’t many options.

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“There are no highly active alternatives for these patients, and the response rate after a platinum-based doublet in a RET-altered tumor … would be typically in the 10, 12, 15% range,” Boral said. Additionally, data suggest checkpoint inhibitors like Keytruda aren’t as active in RET-driven cancers, he said.

RELATED: Blueprint reports promising phase 1 data in RET-altered tumors: AACR

Of the 35 evaluable NSCLC patients who were previously treated, 90% of them had some tumor shrinkage, as seen by imaging, and 60% had a big enough size decrease to be called responders. The treatment eliminated one patient’s cancer and stopped cancer growth in all 35 patients.

BLU-667 also fared well in patients whose cancer had spread to the brain. It shrank brain tumors in seven of the nine patients whose brain metastases were large and defined enough to be seen on a CT scan or with an MRI.

“We’re finding that BLU-667 seems to prevent progression in the brain just like it does elsewhere, so we are not seeing the brain as a site of failure,” Boral said.

Most patients with brain metastases don’t have measurable disease, he said, the metastases being too small or having indistinct borders. But this figure is encouraging, he said.

The study also tested BLU-667 in patients with RET-altered medullary thyroid cancer (MTC), shrinking tumors in 63% of patients who had previously been treated with Sanofi Genzyme’s Caprelsa or Exelixis’ Cabometyx. Five out of six patients with papillary thyroid cancer—which is less aggressive than MTC—responded to BLU-667. After getting its NSCLC filing submitted, Blueprint plans to file BLU-667 for approval in patients with previously treated MTC.

Of note, four patients—two with NSCLC and two with MTC—had previously been treated with Loxo Oncology’s experimental RET inhibitor LOXO-292. Loxo reported promising data at last year’s ASCO meeting, showing its treatment shrank 69% of RET-altered solid tumors

The overall response rate in these RET fusion-positive patients came in at 69%. The tumors of the patients shrunk in size by as much as 67%.

Beyond these first two filings, Blueprint wants to move BLU-667 into earlier-line settings in both lung and thyroid cancers and get into other RET-altered cancers. The study enrolled two patients with pancreatic cancer—one of whom has responded to BLU-667—and one patient with bile duct cancer.

RELATED: Loxo RET inhibitor shines in early-phase trial

Boral spoke about these other cancer types as “baskets” Blueprint wants to fill with “a broad array of different tumors.”

“We see this as another approval opportunity and we have been talking to the FDA about it. If we can get a diverse array of diseases with good response rates, that would be the next step forward,” he said. “But I think what’s even more important is moving into earlier lines of lung cancer.”

The study focused on patients with advanced cancer, but it enrolled a handful of patients who had not received prior treatment. BLU-667 shrank tumors in five of the seven patients—a 71% response rate. This echoes the performance of Genentech’s Alecensa (alectinib), an ALK inhibitor that shrinks tumors in about 55% of patients who have relapsed but does so in about 70% as a first-line therapy, Boral said.

In all, it will be a busy year for Blueprint, with its first FDA filing—for its KIT and PDGFRA inhibitor avapritinib—coming later this month, and a phase 3 study for BLU-667 as a frontline treatment kicking off later in 2019.

Editor's note: This story has been updated to correct the number of patients in the study who had papillary thyroid cancer who responded to BLU-667. It was five out of six patients, not three out of five.

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