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AbbVie announced new data from Cohort 3 of its Phase 2 REFINE study of investigational navitoclax in combination with ruxolitinib in JAK inhibitor-nave patients with myelofibrosis MF. The exploratory analysis suggests the combination of navitoclax and ruxolitinib led to reductions in bone marrow fibrosis BMF and variant allele frequency VAF for common genetic mutations found in individuals with myelofibrosis that may indicate potential disease modification.1 The findings were shared in an oral presentation abstract 237 at the 64th American Society of Hematology Annual Meeting Exposition ASH.While the current standard of care for patients with myelofibrosis can improve disease symptoms impact on underlying disease biology is limited. It is our hope that patients have an option that goes beyond symptom control said Mohamed Zaki M.D. Ph.D. vice president and global head of oncology clinical development AbbVie. Consistent with previous evidence these results suggest navitoclax combination may have disease modifying potential both as an anti-fibrosis agent and by reducing variant allele frequency of driver mutations.REFINE NCT03222609 is a Phase 2 non-randomized open-label multi-cohort study evaluating the safety and efficacy of navitoclax alone or in combination with ruxolitinib in MF.2These data build on AbbVies history of transforming standards of care in blood cancers including recent presentations of investigational navitoclax data from the REFINE study earlier this year at the American Association for Cancer Research AACR Annual Meeting and the European Hematology Association EHA Annual Congress. The findings presented at ASH were based on an exploratory analysis of 32 JAK inhibitor-nave patients with MF from Cohort 3 of the Phase 2 REFINE study. The primary endpoint was spleen volume reduction of 35 percent SVR35 from baseline at week 24.1 Key secondary and exploratory endpoints evaluated in this analysis were a reduction in BMF and a reduction in VAF for the driver gene mutations JAK2V617 CALR MPL or Triple-negative respectively.1In this exploratory analysis SVR35 at week 24 was observed in higher-risk groups improving over time. The four poor prognosis subgroups were Type primary or secondary of MF primary MF 59 percent n 1017 age 75 years 50 percent n 48 prognostic risk score as measured by Dynamic International Prognostic Scoring System or DIPSS intermediate-2 63 percent n 1219 high 33 percent n 13 and presence of high molecular risk HMR mutations 47 percent n 919.1In Cohort 3 BMF grade improvement was evaluable in 81 percent 2632 of patients.1 Of these study participants 35 percent 926 achieved 1 grade improvement at any time during treatment with a median time-to-improvement of 12.3 weeks.1 Complete resolution of BMF was observed in 22 percent 29 of patients.1Reduction in driver gene mutation VAF 20 from baseline at week 12 or 24 was observed in 50 percent 1428 of patients while 18 percent 528 of patients achieved 50 VAF reduction from baseline. There were no differences in 20 VAF reductions from baseline to week 12 or 24 between those with or without HMR mutations 47 percent 715 versus 54 percent 713 respectively.Preliminary safety analysis identified no new safety signals. Twenty-five 78 percent patients reported one or more adverse events AE. The most common grade 3 AEs were thrombocytopenia 47 percent anemia 34 percent and neutropenia 25 percent. 9.4 percent of patients discontinued therapy due to an AE.3These results are promising for patients who need a treatment option that goes beyond just symptom control said Francesco Passamonti full professor of hematology University of Insubria and chief hematology Varese Hospital Italy. The suggestion of disease modification in this analysis from combination therapy with navitoclax is encouraging particularly when combined with clinical efficacy in terms of SVR35 rates in the higher risk groups that improved over time. About NavitoclaxNavitoclax is an investigational oral BCL-XLBCL-2 inhibitor. Navitoclax is not approved by any health authority worldwide at this time. Its safety and efficacy are under evaluation as part of ongoing Phase 2 and registrational Phase 3 studies.AbbVie has an extensive late-stage clinical trial program for investigational navitoclax that is currently enrolling. Please visit us here for more information about enrolling in a clinical trial.
