Avapritinib yields high response rate in patients with systemic mastocytosis

ATLANTA – An oral investigational drug with specific activity against a mutation frequently found in advanced systemic mastocytosis (ASM) produced clinical responses in the majority treated patients, according to preliminary data presented at the annual meeting of the American Society of Hematology.

Mitchel L. Zoler/Frontline Medical News

Avapritinib, previously known as BLU-285, was well tolerated in the phase 1 trial, and demonstrated encouraging preliminary activity that included a 56% rate of complete or partial response, according to lead study author Daniel J. DeAngelo, MD, PhD, director of clinical and translational research at Dana-Farber Cancer Institute, Boston.

Currently, midostaurin, a multikinase inhibitor, is the only Food and Drug Administration–approved drug for the treatment of systemic mastocytosis. That approval, announced in April 2017, was based in part on a 17% rate of complete or partial response, Dr. DeAngelo noted at a press briefing.

The primary goal of the phase 1 trial was to evaluate the safety profile and establish a maximum-tolerated dose for once-daily oral avapritinib administration. Treatment-emergent side effects were primarily grade 1-2, according to Dr. DeAngelo. Most hematologic toxicities were mild to moderate, and the most common grade 3 nonhematologic toxicities were periorbital edema and fatigue.

This part of the phase 1 trial enrolled 18 patients with ASM, systemic mastocytosis with associated hematologic neoplasm (SM-AHN), and mantle cell lymphoma (MCL). Efficacy of avapritinib was assessed on International Working Group criteria for response rate in myelodysplasia.

The overall response rate was 72% (13 of 18 patients saw complete response, partial response, or clinical improvement), and a 56% rate of complete and partial response (10 of 18 patients), Dr. DeAngelo said.

Avapritinib was active in all ASM subtypes evaluated, including in patients who had previously been treated with midostaurin or chemotherapy, according to the investigators.

The data on avapritinib suggests the drug “has a potent and clinically important activity in systemic mastocytosis,” he said. “It has been a wonderful success in terms of getting the majority of patients into complete and partial remissions, and so as this evolves, having better targeted agents, I think, can improve the outcome for these patients.”

More patients are being enrolled as the phase 1 study continues into the dose-expansion phase at 300 mg once daily, and 30 of 32 patients remain on treatment with median duration of 9 months, Dr. DeAngelo said.

A phase 2 study in advanced systemic mastocytosis is planned for 2018, as well as phase 1 and phase 2 studies that will include patients with indolent or smoldering disease, he added.

Avapritinib is manufactured by Blueprint Medicines, which also supported the study. Dr. DeAngelo reported disclosures from Blueprint and several other companies in the hematologic space.

SOURCE: DeAngelo D et al. ASH 2017 Abstract 2.

ATLANTA – An oral investigational drug with specific activity against a mutation frequently found in advanced systemic mastocytosis (ASM) produced clinical responses in the majority treated patients, according to preliminary data presented at the annual meeting of the American Society of Hematology.

Mitchel L. Zoler/Frontline Medical News

Avapritinib, previously known as BLU-285, was well tolerated in the phase 1 trial, and demonstrated encouraging preliminary activity that included a 56% rate of complete or partial response, according to lead study author Daniel J. DeAngelo, MD, PhD, director of clinical and translational research at Dana-Farber Cancer Institute, Boston.

Currently, midostaurin, a multikinase inhibitor, is the only Food and Drug Administration–approved drug for the treatment of systemic mastocytosis. That approval, announced in April 2017, was based in part on a 17% rate of complete or partial response, Dr. DeAngelo noted at a press briefing.

The primary goal of the phase 1 trial was to evaluate the safety profile and establish a maximum-tolerated dose for once-daily oral avapritinib administration. Treatment-emergent side effects were primarily grade 1-2, according to Dr. DeAngelo. Most hematologic toxicities were mild to moderate, and the most common grade 3 nonhematologic toxicities were periorbital edema and fatigue.

This part of the phase 1 trial enrolled 18 patients with ASM, systemic mastocytosis with associated hematologic neoplasm (SM-AHN), and mantle cell lymphoma (MCL). Efficacy of avapritinib was assessed on International Working Group criteria for response rate in myelodysplasia.

The overall response rate was 72% (13 of 18 patients saw complete response, partial response, or clinical improvement), and a 56% rate of complete and partial response (10 of 18 patients), Dr. DeAngelo said.

Avapritinib was active in all ASM subtypes evaluated, including in patients who had previously been treated with midostaurin or chemotherapy, according to the investigators.

The data on avapritinib suggests the drug “has a potent and clinically important activity in systemic mastocytosis,” he said. “It has been a wonderful success in terms of getting the majority of patients into complete and partial remissions, and so as this evolves, having better targeted agents, I think, can improve the outcome for these patients.”

More patients are being enrolled as the phase 1 study continues into the dose-expansion phase at 300 mg once daily, and 30 of 32 patients remain on treatment with median duration of 9 months, Dr. DeAngelo said.

A phase 2 study in advanced systemic mastocytosis is planned for 2018, as well as phase 1 and phase 2 studies that will include patients with indolent or smoldering disease, he added.

Avapritinib is manufactured by Blueprint Medicines, which also supported the study. Dr. DeAngelo reported disclosures from Blueprint and several other companies in the hematologic space.

SOURCE: DeAngelo D et al. ASH 2017 Abstract 2.

ATLANTA – An oral investigational drug with specific activity against a mutation frequently found in advanced systemic mastocytosis (ASM) produced clinical responses in the majority treated patients, according to preliminary data presented at the annual meeting of the American Society of Hematology.

Mitchel L. Zoler/Frontline Medical News

Avapritinib, previously known as BLU-285, was well tolerated in the phase 1 trial, and demonstrated encouraging preliminary activity that included a 56% rate of complete or partial response, according to lead study author Daniel J. DeAngelo, MD, PhD, director of clinical and translational research at Dana-Farber Cancer Institute, Boston.

Currently, midostaurin, a multikinase inhibitor, is the only Food and Drug Administration–approved drug for the treatment of systemic mastocytosis. That approval, announced in April 2017, was based in part on a 17% rate of complete or partial response, Dr. DeAngelo noted at a press briefing.

The primary goal of the phase 1 trial was to evaluate the safety profile and establish a maximum-tolerated dose for once-daily oral avapritinib administration. Treatment-emergent side effects were primarily grade 1-2, according to Dr. DeAngelo. Most hematologic toxicities were mild to moderate, and the most common grade 3 nonhematologic toxicities were periorbital edema and fatigue.

This part of the phase 1 trial enrolled 18 patients with ASM, systemic mastocytosis with associated hematologic neoplasm (SM-AHN), and mantle cell lymphoma (MCL). Efficacy of avapritinib was assessed on International Working Group criteria for response rate in myelodysplasia.

The overall response rate was 72% (13 of 18 patients saw complete response, partial response, or clinical improvement), and a 56% rate of complete and partial response (10 of 18 patients), Dr. DeAngelo said.

Avapritinib was active in all ASM subtypes evaluated, including in patients who had previously been treated with midostaurin or chemotherapy, according to the investigators.

The data on avapritinib suggests the drug “has a potent and clinically important activity in systemic mastocytosis,” he said. “It has been a wonderful success in terms of getting the majority of patients into complete and partial remissions, and so as this evolves, having better targeted agents, I think, can improve the outcome for these patients.”

More patients are being enrolled as the phase 1 study continues into the dose-expansion phase at 300 mg once daily, and 30 of 32 patients remain on treatment with median duration of 9 months, Dr. DeAngelo said.

A phase 2 study in advanced systemic mastocytosis is planned for 2018, as well as phase 1 and phase 2 studies that will include patients with indolent or smoldering disease, he added.

Avapritinib is manufactured by Blueprint Medicines, which also supported the study. Dr. DeAngelo reported disclosures from Blueprint and several other companies in the hematologic space.

SOURCE: DeAngelo D et al. ASH 2017 Abstract 2.