On May 6, 2026 Aptevo Therapeutics Inc. (Nasdaq:APVO) reported new clinical results from its RAINIER frontline acute myeloid leukemia (AML) trial. The Company is on track to complete the Phase 1b dose-optimization trial and select the recommended Phase 2 dose (RP2D) this year. As with the current study, the Phase 2 trial will dose mipletamig in combination with venetoclax and azacitidine.
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Across 31 evaluable frontline AML patients treated to date (includes data through RAINIER Cohort 5, plus 4 patients from the previously completed dose expansion trial), mipletamig in combination with venetoclax and azacitidine has demonstrated an 87% clinical benefit rate (CR/CRi/PR) and an 81% remission rate (CR/CRi), with results continuing to reflect a consistent profile of clinical activity and favorable safety as the dataset expands.
With Cohort 5 complete, dosing has progressed through all previously evaluated mipletamig dose levels. The trial has now entered its final stage, which includes:
Two final dose-level cohorts-Cohorts 6 and 7-representing the highest dose levels of mipletamig evaluated. Enrollment in Cohort 6 is nearing completion
Two groups of six additional patients will be enrolled at select dose levels, with the first enrolling concurrently with Cohort 6
These activities will complete the dataset required for RP2D selection and the planned Phase 2 regulatory interaction, with the trial on track for completion this year.
"With the completion of Cohort 5, we have evaluated mipletamig across all previously studied dose levels and have entered the final stage of the RAINIER trial," said Jeff Lamothe, President and Chief Executive Officer of Aptevo Therapeutics. "The data is compelling, the remaining work is clearly defined, and the study is on track for completion this year, with the dataset enabling selection of the Phase 2 dose and our advancement into Phase 2. The strength and consistency of the data as it expands gives us confidence in the path forward."
Among the evaluable frontline patient population treated to date (N=31), including 27 patients from the RAINIER trial through Cohort 5 and 4 patients from the completed dose-expansion trial, mipletamig in combination with venetoclax and azacitidine has demonstrated:
87% clinical benefit rate,*demonstrating broad anti-leukemia activity and blast reduction across response categories
81% achieved CR or CRi (remission), comparing favorably to the historical benchmark**.
65% achieved CR (complete remission), comparing favorably to the historical benchmark**
55% of patients who achieved CR/CRi had blast reductions that reached the important measurable residual disease-negative level, a result that is typically associated with stronger, more durable responses
36% of patients with remissions had the TP53 genetic mutation, a high-risk biomarker typically associated with poor prognosis in AML and for which most treatment options frequently fail
6 patients treated to date have proceeded to allogeneic stem cell transplant, which represents the best possible outcome in AML treatment and is rarely achieved in the older or unfit frontline patient population
No cytokine release syndrome reported
*Clinical benefit rate, including complete remission (CR), complete remission with incomplete hematologic recovery (CRi), and partial remission (PR)
**In the Phase 3 VIALE-A trial evaluating venetoclax plus azacitidine in frontline intent-to-treat AML patients who were ineligible for intensive induction chemotherapy, the reported composite CR/CRi rate was 66.4%, and the CR rate was 37% (DiNardo et al., New England Journal of Medicine, 2020).
Collectively, these data outperform the benchmark** and demonstrate mipletamig’s potential to meaningfully enhance frontline AML treatment in older and/or unfit patients by improving efficacy outcomes without materially increasing toxicity.
"Our results demonstrate a consistent pattern of clinical activity and favorable safety across patients treated to date," said Dirk Huebner, M.D., Chief Medical Officer of Aptevo Therapeutics. "As dose selection progresses, the focus is on identifying a Phase 2 dose that is supported by a complete and well-characterized dataset."
About the RAINIER Trial
RAINIER, a frontline AML study, is a Phase 1b/2 dose-optimization, multi-center, multi-cohort, open-label study. Subjects are adults aged 18 or older, newly diagnosed with AML, who are not eligible for intensive induction chemotherapy. RAINIER will be conducted in two parts: first, a Phase 1b dose-optimization study in frontline AML patients, followed by a Phase 2 study. The Phase 1b trial consists of 28-day cycles of treatment across multiple sequential cohorts.
About Mipletamig
Aptevo’s wholly owned lead proprietary drug candidate, mipletamig, being evaluated for the treatment of AML, is differentiated by design to redirect the immune system of the patient to destroy leukemic cells and leukemic stem cells expressing the target antigen CD123, which is a compelling target for AML due to its overexpression on leukemic stem cells and AML blasts. This antibody-like recombinant protein therapeutic is designed to engage both leukemic cells and T cells of the immune system and bring them closely together to trigger the destruction of leukemic cells.
Mipletamig is purposefully designed to reduce the likelihood and severity of CRS by use of the CRIS-7-derived CD3 binding pathway, an approach that differentiates Aptevo from competitors. Mipletamig has received orphan drug designation ("orphan status") for AML under the Orphan Drug Act. Orphan drug designation provides key advantages-including the opportunity to seek U.S. market exclusivity for a specific period of time upon approval, FDA fee reductions, and access to development and tax credits. Mipletamig has been evaluated in more than 120 patients over three trials to date.
(Press release, Aptevo Therapeutics, MAY 6, 2026, View Source [SID1234665215])