Blueprint Medicines has dosed the first patient in the Phase 1 study assessing the RET inhibitor BLU-667 in patients with non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC), and other advanced solid tumors with RET mutations.
“By rapidly initiating a clinical trial for our potent and selective RET inhibitor BLU-667, we have successfully achieved a key 2017 milestone,” Jeff Albers, CEO of Blueprint Medicines, said in a press release.
“BLU-667 has a unique product profile differentiated from our other clinical-stage programs by its potential to address predicted resistance mutations that may arise,” he said. “With BLU-667 enrollment underway, we are further increasing our diversified pipeline of potent, highly selective investigational medicines that target specific disease drivers in genomically-defined patient populations.”
RET fusions and mutations are key drivers of multiple cancers, including lung and thyroid cancers, and research suggests they may also play a role in colon and breast cancers.
While several approved drugs are thought to inhibit RET activity, there are currently no approved therapies that selectively target these cancers.
Data from preclinical studies has demonstrated that BLU-667 not only targets cancers driven by mutations in the RET protein, it also targets predicted mutations that render cells resistant to currently approved drugs. This activity suggests it has the ability to prevent or delay cancer recurrence.
The newly started Phase 1 trial (NCT03037385) is an open-label, first-in-human, dose escalation and expansion study designed to investigate the safety, tolerability, and preliminary activity of BLU-667. The study is expected to enroll up to 115 patients with NSCLC, MTC, or other advanced solid tumors who have RET fusions or mutations.
In the first part of the study, the dose-escalation part, 35 patients will receive multiple ascending doses of BLU-667 to establish the maximum dose tolerated by patients (MTD).
Once the MTD, or a recommended dose is established, the trial is expected to enroll an additional 80 patients into the expansion phase of the trial. The study’s primary outcome is safety and changes in clinical laboratory results, and secondary outcomes include the number of patients who experienced tumor regression and the duration of response. Pharmacokinetics (how the drug moves in the body) parameters will also be examined.
“RET fusions and mutations are recognized as important drivers in multiple cancers, but existing multi-kinase inhibitors with RET activity do not provide sufficient, durable benefit for patients with RET alterations,” said Andy Boral, MD, PhD, chief medical officer of Blueprint Medicines.
“BLU-667 is being developed to potently inhibit RET, and simultaneously prevent the development of on-target resistance, which we believe will provide more lasting clinical benefit and prevent or delay disease recurrence. We look forward to working with patients and physicians to explore BLU-667’s potential,” Boral added.