Constellation Pharmaceuticals announces presentation of MANIFEST data at ASCO
Constellation Pharmaceuticals announced the presentation of updated interim data from MANIFEST, the company's Phase 2 clinical trial of CPI-0610 in refractory myelofibrosis, or MF. The interim data, which highlight the tolerability and potentially disease-modifying activity of CPI-0610, were presented in a poster at the annual meeting of the American Society for Clinical Oncology, or ASCO. The data were gathered from 44 patients enrolled as of April 17. Twelve patients received 24-week assessments and 16 patients received 12-week assessments. Fourteen 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, or TSS, according to the Myelofibrosis Symptom Assessment Form. Six of the 11 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, or PGIC. Fifteen of 16 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 and remain on trial.mTen patients were evaluable for bone marrow fibrosis, of which six 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 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 April 17.