AbbVie Presents Positive Navitoclax Combination Data for Treatment of Myelofibrosis

AbbVie presented new data at the American Association for Cancer Research Annual Meeting 2022 from a phase 2 trial of navitoclax in combination with ruxolitinib in individuals with myelofibrosis.

Navitoclax is a first-in-class, investigational, oral BCL-XL/BCL-2 inhibitor that is designed to activate programmed cell death, known as apoptosis, in cancer cells.

The drug’s efficacy and safety are under evaluation as part of ongoing phase 2 and registrational phase 3 studies.

“Myelofibrosis is a cancer that originates in the bone marrow, leading to fibrosis. Currently, available therapies do not address the underlying disease biology and have not shown a consistent effect on both biomarkers of disease modification and overall survival [OS],” Mohamed Zaki, MD, PhD, vice president and global head of oncology clinical development at AbbVie, said in a statement.

“Disease control with reversal of bone marrow fibrosis [BMF] is a key objective for improving patient outcomes," he said.

The data are from the REFINE trial, a phase 2 trial that evaluated navitoclax in combination with ruxolitinib, which included individuals with myelofibrosis who had progressed on or had a suboptimal response to at least 12 weeks of ruxolitinib monotherapy.

Median exposure to prior ruxolitinib was 91 weeks in the first 34 individuals enrolled earlier in the trial.

In the exploratory analysis of 32 individuals who could be evaluated for improvements in BMF, 12 had a 1-grade or higher improvement during any time point in the study.

For driver gene VAF reduction, 26 individuals could be evaluated, and 6 achieved a 20% or greater reduction at week 24. Additionally, 5 individuals achieved both BMF and VAF responses.

“What is most notable in this analysis is the [OS] among patients who demonstrate VAF and BMF responses, and all patients were alive at time of analysis. Patients in this phase 2 trial had suboptimal response to ruxolitinib at time of study entry and then had navitoclax added to ruxolitinib on the trial,” Jacqueline Garcia, MD, assistant professor of medicine at Harvard Medical School, said in the statement.

“VAF and BMF responses occurred, despite the presence of high molecular risk mutations, which suggests the potential efficacy of combination navitoclax and ruxolitinib could be independent of underlying risk factors,” she said.

The median OS for all individuals was not reached as presented previously. For individuals who had a 1-grade or higher improvement in BMF, median OS was not reached compared with 28.5 months for individuals who did not experience an improvement.

Similarly, the median OS was also not reached for individuals who achieved a 20% or more driver gene VAF reduction versus 28.5 months for individuals who did not.

All 34 individuals did experience at least 1 adverse event (AE), and 15 individuals experienced serious AEs. The most common AEs of any grade were diarrhea, fatigue, nausea, and thrombocytopenia.

The most common serious AEs were pneumonia and splenic infarction.

There were no serious bleeding-related AEs, and thrombocytopenia was manageable and reversible with dose reduction or interruption of navitoclax and/or ruxolitinib.

Reference

AbbVie presents positive investigational navitoclax combination data in phase 2 REFINE study suggesting anti-fibrosis activity for patients with myelofibrosis. AbbVie. News release. April 12, 2022. Accessed April 12, 2022. https://news.abbvie.com/news/press-releases/abbvie-presents-positive-investigational-navitoclax-combination-data-in-phase-2-refine-study-suggesting-anti-fibrosis-activity-for-patients-with-myelofibrosis.htm