Constellation Pharmaceuticals Enhances and Expands Phase 2 MANIFEST Study of CPI-0610 in Myelofibrosis
– Amends second-line trial design to stratify for transfusion dependence based on positive preliminary data –
– Expands study to include an additional arm evaluating CPI-0610 as first-line therapy in combination with ruxolitinib in JAK-inhibitor-naïve myelofibrosis (MF) patients –
– Maintains prior guidance for determining proof of concept by mid-2019 –
– Company to host conference call at
MANIFEST is evaluating CPI-0610, either as a monotherapy or in combination with ruxolitinib, in patients with MF who are refractory or intolerant or have relapsed or lost response to the standard of care. Based on encouraging preliminary data in this trial, Constellation is amending the design of each second-line cohort to stratify all patients enrolled in the study based on transfusion dependence status. In addition, the Company is amending the design of MANIFEST to include a third cohort designed to evaluate treatment with CPI-0610 in combination with ruxolitinib as a first-line therapy in JAK 1/2-inhibitor-naïve MF patients.
The Company made these updates based on the unmet medical need for disease-modifying therapies in myelofibrosis, especially among patients requiring red-blood-cell transfusions. The changes are intended to enhance the clinical trial design by providing additional measures of potential clinical benefit and to expand the potential addressable patient population for CPI-0610.
“We are encouraged by the preliminary data from MANIFEST, which may indicate synergistic and disease-modifying effects of CPI-0610 in myelofibrosis,” said
The Phase 2 proof-of-concept portion of MANIFEST in a second-line setting is designed to study the anti-tumor activity and safety of the
As a result of this positive preliminary hematological data, all enrolled patients in both the combination and monotherapy arms will now be stratified by transfusion dependence status, with each cohort expected to enroll up to 16 transfusion-dependent patients and up to 25 non-transfusion-dependent patients. Proof of concept in these cohorts will be based on conversion to transfusion independence and other factors in transfusion-dependent patients; and by reduction in spleen volume, patient-reported symptom improvement, and other factors in non-transfusion-dependent patients.
In addition, Constellation is adding a third cohort to this trial, which will evaluate treatment with CPI-0610 in combination with ruxolitinib as first-line therapy in up to 43 JAK 1/2-inhibitor-naïve MF patients. This cohort will only enroll anemic patients. Constellation’s current plan for a potential pivotal trial of CPI-0610 as a first-line treatment would be to enroll all-comers. Proof of concept for this cohort will be measured by reduction in spleen volume, patient-reported symptom improvement, and other factors.
The Company expects to update this protocol change at https://clinicaltrials.gov under study ID NCT02158858 in the near future.
Conference Call/Corporate Presentation
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 development status of the Company’s product candidates, the anticipated benefits of the changes to its clinical trial protocols and its anticipated achievement of milestones, including determination of proof of concept. 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
MacDougall Biomedical Communications
Source: Constellation Pharmaceuticals