Blueprint Medicines Announces New Data from Ongoing Phase 1 Clinical Trial of BLU-285 in Patients with Advanced Gastrointestinal Stromal Tumors Showing Strengthened Clinical Activity across Spectrum of KIT and PDGFRα Genotypes
As previously announced,
"The updated BLU-285 data show robust clinical activity in a broad population of patients with advanced GIST," said
"We are grateful to the patients, families and investigators who have contributed to the Phase 1 clinical trial to date, and we are committed to advancing the clinical development of BLU-285 quickly and responsibly," said
New Data from the Ongoing Phase 1 Clinical Trial of BLU-285 in Advanced GIST
As of the data cutoff date of
As of the data cutoff date, BLU-285 was generally well-tolerated. Most AEs reported by investigators were Grade 1 or 2. Across all grades, the most common treatment-emergent AEs reported by investigators (≥20 percent) included nausea (56 percent), fatigue (53 percent), periorbital edema (43 percent), vomiting (41 percent), edema peripheral (34 percent), anemia (31 percent), diarrhea (31 percent), increased lacrimation (30 percent), cognitive effects (30 percent), decreased appetite (28 percent), dizziness (23 percent), constipation (22 percent) and hair color changes (22 percent). Cognitive effects are an aggregated category of individual cognitive events, each of which was observed in fewer than 20 percent of patients. Investigators reported treatment-related Grade ≥3 AEs in 39 patients (34 percent), including anemia (9 percent), fatigue (7 percent), hypophosphatemia (4 percent), nausea (4 percent) and cognitive effects (3 percent). Six patients (5 percent) discontinued treatment with BLU-285 due to AEs. An additional 43 patients discontinued treatment, with 40 patients due to progressive disease and three patients who withdrew consent. Among all 116 enrolled patients, 67 remained on treatment as of the data cutoff date.
Clinical Activity Data:
As of the data cutoff date, 30 patients with KIT-driven GIST treated at 300 to 400 mg QD were evaluable for response assessments. In addition, 31 patients with PDGFRα D842-driven GIST at all doses were evaluable for response assessments, including 29 patients with a D842V mutation and two patients with other D842 mutations. Two patients with a PDGFRα exon 14 mutation were excluded from analyses of clinical activity. Patients were evaluable if they had at least one centrally reviewed radiographic scan, and all reported data are based on blinded central radiology review as per modified Response Evaluation Criteria in Solid Tumors version 1.1 (mRECIST 1.1 criteria) for GIST. Radiographic scans were also assessed by Choi criteria, a supportive method of response assessment in soft tissue sarcomas that has been shown to be predictive of improved prognosis in patients with advanced GIST.
Patients with heavily pretreated KIT-driven GIST treated at doses of 300 to 400 mg QD
- Centrally assessed radiographic tumor reductions were observed in 20 of 30 evaluable patients (67 percent) across all common KIT genotypes, including mutations in exons 9, 11, 13, 14 and 17, confirmed by archival tumor biopsy and circulating tumor DNA.
- By mRECIST 1.1 criteria, five patients had a partial response (PR) (three confirmed, two pending confirmation), and 18 patients had stable disease (SD), representing an ORR of 17 percent and a disease control rate (DCR) of 77 percent.
- By Choi criteria, 16 patients had a PR and seven patients had SD, representing an ORR of 53 percent and a DCR of 77 percent.
- Median PFS was 11.5 months.
- In contrast, historical data showed a zero percent ORR and median PFS of 1.8 months in patients with TKI-resistant advanced GIST re-treated with imatinib in a third-line or later setting.1
Patients with PDGFRα-driven GIST
- Centrally assessed radiographic tumor reductions were observed in all 31 evaluable patients.
- By mRECIST 1.1 criteria, one patient had a complete response (CR) (pending confirmation), 21 patients had a PR (18 confirmed, three pending confirmation), and nine patients had SD, representing an ORR of 71 percent and a DCR of 100 percent.
- By Choi criteria, one patient had a CR and 30 patients had a PR, representing an ORR of 100 percent.
- Median PFS was not reached, and 12-month PFS was estimated to be 78 percent.
- In contrast, historical data showed a zero percent ORR and median PFS of 2.8 months in patients with PDGFRα D842V-driven GIST treated with imatinib.2
About the Phase 1 Clinical Trial for BLU-285 in PDGFRα-Driven and KIT-Driven GIST
The Phase 1 clinical trial of BLU-285 is designed to evaluate the safety and tolerability of BLU-285 in adults with advanced GIST. The trial consists of two parts, a dose-escalation portion and an expansion portion. The dose-escalation portion is complete, and the MTD was determined to be 400 mg QD.
GIST is the most common sarcoma, or tumor of bone or connective tissue, of the gastrointestinal (GI) tract. Tumors arise from cells in the wall of the GI tract and occur most often in the stomach or small intestine. Most patients are diagnosed between the ages of 50-80, and diagnosis is typically triggered by GI bleeding, incidental findings during surgery or imaging and, in rare cases, tumor rupture or GI obstruction. Approximately 80 percent of GIST patients have KIT-driven GIST, and Blueprint Medicines estimates that KIT exon 17 mutations occur in approximately 90 percent of GIST patients with KIT-driven GIST following treatment with at least two TKIs. Approximately five percent of all advanced GIST cases are driven by D842V mutant PDGFRα. Patients diagnosed with GIST at an early stage may undergo surgery. For patients with KIT-driven GIST, treatment with the currently approved frontline therapy typically leads to treatment resistance and disease progression. Treatment options for KIT-driven GIST patients whose disease progresses or develops resistance are currently limited, with approved therapies providing a progression free survival of up to six months and a response rate between five percent and seven percent. There are no effective treatment options for patients with PDGFRα D842V-driven GIST, and progression often occurs in as little as three months with available treatment options.
BLU-285 is an orally available, potent and highly selective inhibitor of KIT and PDGFRα. Preclinical data have shown that BLU-285 is active across a broad spectrum of KIT and PDGFRα mutations, including PDGFRα D842V and KIT exon 17 mutations for which there are limited or no effective treatment options. Blueprint Medicines is initially developing BLU-285, an investigational medicine, for the treatment of patients with advanced GIST and advanced systemic mastocytosis. BLU-285 was discovered by Blueprint Medicines' research team leveraging its proprietary compound library, and the Company retains worldwide development and commercialization rights for BLU-285.
In June 2017, BLU-285 received Breakthrough Therapy Designation from the FDA for the treatment of patients with unresectable or metastatic GIST harboring the PDGFRα D842V mutation. The FDA's Breakthrough Therapy Designation is intended to expedite the development and review of a drug candidate intended to treat a serious or life-threatening disease or condition, when preliminary clinical evidence indicates that the drug candidate may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. Previously, the FDA granted orphan drug designation to BLU-285 for the treatment of GIST. The FDA also granted Fast Track designation to BLU-285 for the treatment of patients with unresectable or metastatic GIST that progressed following treatment with imatinib and a second TKI and for the treatment of patients with unresectable or metastatic GIST in patients with the PDGFRα D842V mutation regardless of prior therapy. In addition, the
About Blueprint Medicines
Blueprint Medicines is developing a new generation of targeted and potent kinase medicines to improve the lives of patients with genomically defined diseases. Its approach is rooted in a deep understanding of the genetic blueprint of cancer and other diseases driven by the abnormal activation of kinases. Blueprint Medicines is advancing four programs in clinical development for subsets of patients with gastrointestinal stromal tumors, hepatocellular carcinoma, systemic mastocytosis, non-small cell lung cancer, medullary thyroid cancer and other advanced solid tumors, as well as multiple programs in research and preclinical development. For more information, please visit www.blueprintmedicines.com.
1 Kang YK, Ryu MH, Ryoo BY, et al. Resumption of imatinib to control metastatic or unresectable gastrointestinal stromal tumours after failure of imatinib and sunitinib (RIGHT): a randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2013;14(12):1175–82.
2 Cassier PA, Fumagalli E, Rutkowski P, et al. Outcome of Patients with Platelet-Derived Growth Factor Receptor Alpha–Mutated Gastrointestinal Stromal Tumors in the Tyrosine Kinase Inhibitor Era. Clin Cancer Res. 2012;18(16):4458–64.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding plans and timelines for the clinical development of BLU-285, including plans and timelines for pursuing expedited development in patients with a PDGFRα D842V mutation and plans and timelines for the initiation of a global, randomized Phase 3 clinical trial of BLU-285 in third-line GIST;
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