A Curis clinical trial under a partial FDA hold for more than a year is now cleared to resume, and the biotech is working with clinical sites to enroll patients whose blood cancers exhibits certain mutations.

The drug, emavusertib, is a small molecule formulated as a pill. Lexington, Massachusetts-based Curis designed the drug to block IRAK4, an enzyme that plays a key role in pathways involved in some cancers and inflammatory diseases.

In April 2022, the FDA placed a partial hold on a Phase 1/2 test of emavusertib in leukemia after a study participant developed rhabdomyolysis, muscle tissue death that is a known dose-limiting complication of the drug. The partial hold stopped the enrollment of new patients but allowed already enrolled participants to continue receiving the experimental therapy.

Four months after placement of the partial clinical hold, the FDA gave Curis permission to resume enrollment of additional patients in the monotherapy dose-finding portion of the study. The company added nine more patients at the 200 mg, twice-a-day dose.

As of a March 17 data cutoff date, Curis said 84 patients had received emavusertib as a monotherapy at doses ranging from 200 mg to 500 mg twice daily. Across all patient groups, the company reported significant reductions in the counts of blasts, the abnormal white blood cells that multiply in leukemia patients.

In subpopulations of evaluable patients treated with the 300 mg, twice-daily dose, Curis said two of three patients with an FLT3 mutation achieved a complete response and two of three patients with a spliceosome mutation achieved a complete response or a complete response with partial hematologic recovery. The duration of these responses ranged from 5.6 to 7 months.

With the lift of the partial hold, Curis said it has selected the 300 mg twice daily dose for Phase 2 testing of emavusertib as a monotherapy in patients with acute myelogenous leukemia or myelodysplastic syndromes. The study will enroll patients with an FLT3 or spliceosome mutation who have received two or more prior lines of treatment. Curis is also planning to start a test of the drug as a front-line therapy in combination with azacitidine and venetoclax, two other drugs used to treat blood cancers.

“We believe emavusertib has the potential to be the cornerstone agent in the treatment of hematological malignancies,” Curis President and CEO James Dentzer said in a prepared statement.

At the end of the first quarter of this year, Curis reported its cash position was $31.7 million. To support its clinical trial plans, Curis has reached an agreement to sell stock to certain existing investors. This registered direct offering will raise about $15 million. Updated data from the monotherapy study are expected in 2024. Initial data from the combination study are also expected next year.

Public domain image from the National Cancer Institute