Interim Data for CPI-0610 in MANIFEST Clinical Trial Showed Signals of Clinical Activity in Myelofibrosis Patients
- CPI-0610 showed signals of clinical activity, both as a monotherapy and in combination with ruxolitinib, in refractory myelofibrosis (MF) patients
- Patients treated with CPI-0610 exhibited improvement in spleen volume, constitutional symptoms, anemia, bone marrow fibrosis, and transfusion dependence
- CPI-0610 was generally well-tolerated as a monotherapy and in combination with ruxolitinib
- Company to host analyst/investor event and webcast
June 4, 2019at 7:00 AM CDT
“We are excited by these interim data from the MANIFEST trial, which indicate that CPI-0610 is generally well-tolerated and showed signs that it is an active therapeutic agent for the treatment of myelofibrosis, both as a monotherapy and in combination with a standard-of-care JAK inhibitor,” said
The data were gathered from 44 patients enrolled as of
- 14 of 16 evaluable patients demonstrated spleen volume reductions. Overall, the median best on-trial spleen volume change from baseline was -19.2%.
- Of these 16 evaluable patients, 11 were evaluable for improvement in Total Symptom Score (TSS) according to the Myelofibrosis Symptom Assessment Form, Version 4.0. Six of the 11 (55%) evaluable patients achieved greater than 50% TSS improvement from baseline as a best response.
- All of these 16 patients were evaluable for Patient Global Impression of Change (PGIC). Fifteen of 16 (94%) evaluable patients reported improvements in PGIC, of which 10 reported feeling either “much improved” or “very much improved” and no patients reported feeling worse following treatment.
- Of 12 evaluable patients who received at least 24 weeks of treatment, three were severely anemic and dependent on red-blood-cell transfusions at baseline. Of these three patients, two converted to transfusion independence. These two patients have remained transfusion independent for more than 69 and 24 weeks, respectively, as of
April 17, 2019, and remain on trial.
- Ten patients were evaluable for bone marrow fibrosis, of which six (60%) experienced improvement in bone marrow morphology of at least one point on a scale of 0-3. Four of these six patients exhibited improvements within six months of starting CPI-0610 therapy.
Based on the interim data, CPI-0610 was generally well-tolerated, both as a monotherapy and in combination with ruxolitinib. Overall, the most commonly reported side effects (≥10%) were diarrhea, vomiting, upper respiratory tract infection, headache, epistaxis, fatigue, dysgeusia, cough and pruritis. Grade 3 or greater treatment-emergent adverse events were only reported in the combination arm, and those reported in more than one patient included thrombocytopenia, anemia, and decreased platelet counts, each of which was reported in two patients. There was one patient death, which the Company assessed as unlikely to have been related to CPI-0610. The combination therapy of CPI-0610 and ruxolitinib showed a non-cumulative, manageable, and mostly reversible asymptomatic thrombocytopenia.
Each of the first four patients enrolled in MANIFEST, of which two received CPI-0610 as a monotherapy and two received CPI-0610 in combination with ruxolitinib, remained on therapy and had been treated for approximately 16 and 20 months, respectively, as of
Please see the poster in the Investors & Media section of Constellation’s website for additional details.
As previously announced in
Constellation will host an analyst/investor meeting, with an accompanying conference call and webcast, to discuss this interim update in the Jackson Park D room at
- An overview of myelofibrosis (MF) and the potential impact of Constellation’s
BETinhibitor CPI-0610 in treating MF
- A review of the interim data from the MANIFEST clinical trial presented in a poster at
ASCOon June 3
- A panel discussion with two key opinion leaders in MF:
Srdan Verstovsek, a medical oncologist at the University of Texas MD Anderson Cancer Centerand an investigator in the MANIFEST trial; and
- Dr. Raajit Rampal, a hematologic oncologist at
Memorial Sloan Kettering Cancer Center
The event will be webcast live and can be accessed on the Investor Relations section of Constellation’s website at http://ir.constellationpharma.com/events-and-presentations/events. Participants may also access the event and participate in the live question-and-answer session by dialing (877) 473-2077 (domestic) or (661) 378-9662 (international) and referring to conference ID 1295319.
Medical Presentation at EHA
MANIFEST is an open-label Phase 2 clinical trial of CPI-0610 in patients with myelofibrosis (MF), a rare cancer of the bone marrow that disrupts the body’s normal production of blood cells. Constellation is evaluating CPI-0610, either as a monotherapy or in combination with ruxolitinib, in a second-line setting in patients with MF who are refractory to or intolerant of or have relapsed or lost response to ruxolitinib. Patients in the two second-line arms are being stratified based on transfusion-dependent status. The primary endpoint for the cohorts with transfusion-dependent patients is conversion to transfusion independence for 12 consecutive weeks. The primary endpoint for the patients who were not transfusion-dependent at baseline is spleen volume reduction. In addition, the Company added a third arm designed to evaluate treatment with CPI-0610 in combination with ruxolitinib as a first-line therapy in JAK-1/2-inhibitor-naïve MF patients.
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding the implications of preliminary or interim clinical data, the development status of the Company’s product candidates, and the Company’s plans for future data presentations. All statements, other than statements of historical facts, contained in this press release, including statements regarding the Company’s strategy, future operations, future financial position, prospects, plans and objectives of management, are forward-looking statements. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with Constellation’s ability to: obtain and maintain necessary approvals from the
Senior Director, Investor Relations
MacDougall Biomedical Communications
Source: Constellation Pharmaceuticals