Aptevo Therapeutics announced breakthrough results from its Phase 1b/2 RAINIER trial, with mipletamig achieving a 100% remission rate in Cohort 3 when combined with venetoclax and azacitidine for newly diagnosed acute myeloid leukemia (AML) patients unfit for intensive chemotherapy. The clinical-stage biotechnology company reported no dose-limiting toxicities or cytokine release syndrome across all trial cohorts to date.
Exceptional Efficacy Results
The 100% remission rate (CR/CRi) achieved at the highest dose level tested represents a significant milestone for frontline AML treatment. Beyond the complete remission rate, 40% of patients treated achieved minimal residual disease (MRD)-negative status, a critical marker strongly associated with improved overall outcomes in AML patients.
"Cohort 3 demonstrates the kind of progress that changes expectations for frontline AML therapy," said Marvin White, President and Chief Executive Officer of Aptevo. "Delivering a 100% remission rate reinforces our conviction that mipletamig is more than an active agent—it's a differentiated medicine designed to integrate with the venetoclax and azacitidine backbone and elevate outcomes for patients who have had too few options for too long."
Favorable Safety Profile
The trial's safety data proved equally compelling, with no dose-limiting toxicities observed across Cohort 3 and the two prior RAINIER cohorts. Tolerability remained strong even at the highest dose tested, distinguishing mipletamig from many emerging AML combinations that struggle with cytokine release syndrome and other immune-related toxicities.
"The Cohort 3 results are exceptional both in depth of response and in consistency," said Dirk Huebner, MD, Chief Medical Officer. "Across the RAINIER trial to date, mipletamig has achieved near-universal remissions while maintaining a safety profile that is very well managed in the clinic. This balance of potency and tolerability is exactly what physicians need to confidently adopt a new frontline regimen."
Novel Mechanism of Action
Mipletamig represents a first-in-class CD123 x CD3 bispecific antibody designed to redirect the patient's immune system to destroy leukemic cells and leukemic stem cells expressing CD123. The target antigen CD123 is compelling for AML treatment due to its overexpression on leukemic stem cells and AML blasts.
The therapeutic is purposefully designed to reduce the likelihood and severity of cytokine release syndrome through use of the CRIS-7-derived CD3 binding pathway, an approach that differentiates Aptevo from competitors. This antibody-like recombinant protein therapeutic engages both leukemic cells and T cells, bringing them together to trigger leukemic cell destruction.
Market Opportunity and Clinical Development
Frontline AML represents a multibillion-dollar global market where current standard regimens achieve lower remission rates than those observed in RAINIER. By consistently delivering remissions across three increasing dose cohorts and among frontline patients in prior trials, mipletamig positions Aptevo to compete in a high-value segment of the AML market.
The RAINIER trial is a Phase 1b/2 dose optimization, multi-center, multi-cohort, open-label study enrolling adults aged 18 or older with newly diagnosed AML who are not eligible for intensive induction chemotherapy. The Phase 1b trial consists of 28-day cycles of treatment across multiple, sequential cohorts, followed by a Phase 2 study.
Regulatory Status and Next Steps
Mipletamig has received orphan drug designation for AML according to the Orphan Drug Act, providing key advantages including the opportunity to seek U.S. market exclusivity for a specific period upon approval, FDA fee reductions, and access to development and tax credits. The drug has been evaluated in more than 100 patients over three trials to date.
Cohort 3 enrollment is complete and Cohort 4 is actively enrolling patients at the next dose level. The company anticipates presenting current findings at a major medical conference in Q4 2025.
