BLU-667 Promising in RET-Altered Solid Tumors

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Doses of at least 60 mg yielded tumor reductions of 2% to 70% among 25 of the 30 evaluated patients.
Doses of at least 60 mg yielded tumor reductions of 2% to 70% among 25 of the 30 evaluated patients.
The following article features coverage from the American Association for Cancer Research (AACR) 2018 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.

BLU-667, a RET inhibitor, may be an effective treatment for patients with RET-altered solid tumors, according to data presented at the 2018 American Association for Cancer Research Annual Meeting in Chicago, Illinois.1

RET is an established oncogene in several cancers, including non–small cell lung cancer (NSCLC) and medullary thyroid cancer (MTC). BLU-667 is a selective and potent inhibitor of RET that may be effective in the clinical setting.

For this phase 1 study, (ClinicalTrials.gov Identifier: NCT03037385), researchers are evaluating the safety, efficacy, and pharmacokinetics of BLU-667 among patients with RET-altered solid tumors. The maximum tolerated dose is also being determined.

Forty-three patients (15 with RET-fusion NSCLC, 26 with RET-mutant MTC, and 2 patients with non-RET cancers) received BLU-667 (dose range, 30-400 mg/day). The median number of previous therapies was 1.

Thirty patients had post-baseline response assessment. Per RECIST 1.1 criteria, the best overall response rate was 37%, including 5 (4 confirmed) partial responses in 11 patients with NSCLC and 5 partial responses (3 confirmed) in 19 patients with MTC. One unconfirmed complete response was observed among patients with MTC.

Doses of at least 60 mg yielded tumor reductions of 2% to 70% among 25 of the 30 evaluated patients.

The maximum tolerated dose was not reached at time of this analysis. Three dose-limiting toxicities were, however, noted (alanine aminotransferase increase, tumor lysis syndrome, and hypertension; all grade 3).

While no grade 4 or 5 adverse events were reported, 6 patients discontinued BLU-667 for progressive disease, 2 discontinued because of adverse events, 1 patient discontinued for an unspecified reason, and 1 patient died.

The authors concluded that “BLU-667, a highly potent and selective RET inhibitor has been well tolerated and demonstrates promising clinical activity in RET-altered solid tumors, including [patients] who have failed multikinase inhibitor therapy.”

Read more of Cancer Therapy Advisor's coverage of the American Association for Cancer Research (AACR) 2018 meeting by visiting the conference page.

Reference

  1. Subbiah V, Taylor M, Lin J, et al. Highly potent and selective RET inhibitor, BLU-667, achieves proof of concept in a phase I study of advanced, RET-altered solid tumors. Oral presentation at: 2018 American Association for Cancer Research Annual Meeting; April 14-18, 2018; Chicago, IL.

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