BLU-667 active in RET-altered thyroid cancer

BLU-667, an investigational once-daily oral RET inhibitor, induced durable responses among patients with advanced RET-altered medullary thyroid cancer or papillary thyroid cancer, according to data presented at the Annual Meeting of the American Thyroid Association.

The agent also appeared well tolerated.

The phase 1 ARROW trial assessed BLU-667 (Blueprint Medicines) among 69 patients, 42 of whom had RET-altered thyroid cancer.

Results showed 90% of evaluable patients with medullary thyroid cancer (n = 35) or papillary thyroid cancer (n = 4) achieved radiographic tumor reductions. Researchers observed responses regardless of RET alteration type or receipt of prior multikinase inhibitor therapy (47% for treated vs. 50% for treatment naive).

Researchers observed a 62% response rate among patients with medullary thyroid cancer treated with 300 mg to 400 mg BLU-667 once daily for at least 24 weeks.

Two of the four patients with papillary thyroid cancer achieved confirmed partial responses.

“Existing treatment of medullary and papillary thyroid cancer with multikinase inhibitors is limited by frequent dose modifications or interruptions due to off-target toxicities, reducing the opportunity for a meaningful or sustained response,” Andy Boral, MD, PhD, chief medical officer of Blueprint Medicines, said in a company-issued press release. “These new data showed selectively targeting RET alterations with BLU-667 was well tolerated and enabled durable responses. Importantly, response rates were high for patients with prolonged time on therapy at higher dose levels, demonstrating that potent and sustained target inhibition leads to improved patient outcomes.”

The safety results appeared consistent with prior data. Researchers observed primarily grade 1 adverse events, including constipation (35%), increased aspartate aminotransferase (33%), anemia (30%), hypertension (30%), decreased white blood cell count (29%), diarrhea (28%), neutropenia (28%), increased alanine aminotransferase (25%), increased blood creatinine (23%), fatigue (19%) and headache (17%).

Grade 3 or higher treatment-related adverse events that occurred among two or more patients included anemia, hypertension, decreased white blood cell count, diarrhea and neutropenia.

Two patients discontinued therapy due to treatment-related adverse events, including grade 3 increased alanine aminotransferase among a patient with liver metastases and grade 2 pneumonitis.

“We believe these results begin to reveal the potential of BLU-667 to transform the care of patients with RET-altered thyroid cancer, and we look forward to seeing the data continue to mature as additional patients are treated at the recommended phase 2 dose for longer durations,” Boral said.

Researchers plan to expand enrollment targets to further evaluate the safety and efficacy of BLU-667.

Reference:

Hu M, et al. Abstract Short Call Oral 5. Presented at: 88th Annual Meeting of the American Thyroid Association; Oct. 3-7, 2018; Washington, D.C.

Disclosure: HemOnc Today could not confirm the authors’ relevant financial disclosures at the time of publication.