Aptevo Therapeutics announced that its bispecific antibody mipletamig, in combination with venetoclax and azacitidine, achieved a 100% remission rate within 30 days in Cohort 1 of the RAINIER Phase 1b trial for frontline acute myeloid leukemia (AML). The results suggest a potential advancement in the treatment of this aggressive blood cancer, particularly for patients ineligible for intensive chemotherapy.
The RAINIER trial is a Phase 1b/2 dose optimization, multi-center, multi-cohort, open-label study evaluating mipletamig in combination with venetoclax and azacitidine. The Phase 1b portion includes five sequential cohorts with 28-day treatment cycles. The trial aims to enroll up to 39 patients newly diagnosed with AML who are not candidates for intensive induction chemotherapy.
Key Findings from Cohort 1
All three patients in Cohort 1 achieved remission within 30 days. Two of these patients experienced complete remission with minimal residual disease (MRD)-negative status, indicating a complete elimination of cancer cells. According to Aptevo's Chief Medical Officer, Dr. Dirk Huebner, achieving MRD-negative status is a critical outcome strongly associated with longer-lasting remissions and improved survival rates.
Impact on TP53-Mutated AML
Notably, one of the MRD-negative patients had a TP53 mutation, a genetic abnormality often linked to poor prognosis in AML due to chemotherapy resistance and genetic instability. This outcome suggests that mipletamig may offer a potential therapeutic benefit for this difficult-to-treat subgroup of AML patients.
Consistent Efficacy and Safety Profile
These results build upon previous data from earlier trials, where 86% of patients achieved remission within 30 days of their first treatment with the mipletamig combination. Aptevo's President and CEO, Marvin White, emphasized that mipletamig continues to demonstrate a favorable safety and tolerability profile, reinforcing its potential as a transformative addition to the standard of care.
Mipletamig: A Novel Bispecific Antibody
Mipletamig is a CD3 x CD123 bispecific antibody designed to redirect the patient's immune system to destroy leukemic cells and leukemic stem cells expressing the CD123 target antigen. CD123 is overexpressed on leukemic stem cells and AML blasts, making it a compelling target for AML therapy. The antibody is designed to bring leukemic cells and T cells of the immune system together, triggering the destruction of leukemic cells. Mipletamig has been granted orphan drug designation for AML.
Next Steps
Enrollment for Cohort 2 of the RAINIER trial is now commencing. Aptevo plans to share new results as they become available, continuing to evaluate the potential of mipletamig in improving outcomes for patients with AML.
