On September 3, 2026 Aptevo Therapeutics Inc. (Nasdaq:APVO), a clinical-stage biotechnology company developing novel multispecific immuno-oncology therapeutics, reported a 93% clinical benefit rate with its mipletamig triplet in evaluable frontline acute myeloid leukemia (AML) patients with TP53 mutations, one of the most difficult-to-treat forms of the disease and a patient population that has historically responded poorly to treatment.
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"TP53-mutated AML remains one of the most challenging AML subpopulations to treat," said Dirk Huebner, M.D., Chief Medical Officer of Aptevo. "Seeing this level of clinical benefit with the mipletamig triplet in a patient population that historically has not responded well to treatment is exciting. These results support mipletamig as a promising frontline treatment for one of the most difficult-to-treat forms of AML."
Of 14 evaluable TP53-mutated patients treated with mipletamig in combination with venetoclax and azacitidine, including two patients from the previously completed dose expansion trial, 13 (93%) experienced clinical benefit.* Eleven patients achieved CR or CRi (79%), including nine complete remissions.
*Clinical benefit includes complete remission (CR), complete remission with incomplete hematologic recovery (CRi), partial response (PR) and morphologic leukemia-free state (MLFS).
These results are encouraging because patients with TP53-mutated AML have historically had limited treatment success. The 79% CR/CRi rate observed with the mipletamig triplet compares favorably with a published 41% composite remission rate** for venetoclax plus azacitidine in treatment-naïve patients with poor-risk cytogenetics and TP53-mutated AML.
**Benchmark comparison based on Pollyea DA, et al. Clinical Cancer Research. 2022;28(24):5272-5279. Comparison is to treatment-naïve patients with poor-risk cytogenetics and TP53-mutated AML treated with venetoclax plus azacitidine.
TP53-mutated AML is one of the most difficult forms of acute myeloid leukemia to treat, with patients historically experiencing lower remission rates and poorer outcomes than those with other forms of AML. Because TP53 mutations can make leukemia cells more resistant to treatment, achieving deep and durable responses in this patient population has been particularly challenging. As a result, the robust responses observed with mipletamig in TP53-mutated AML are especially encouraging and highlight its potential to address a significant unmet medical need.
Currently, the RAINIER study is evaluating mipletamig in combination with venetoclax and azacitidine in frontline AML patients who are unfit to receive standard high-intensity chemotherapy in a dose optimization trial. This phase of the trial is expected to be completed by year-end, and regulatory interaction is planned for 1H27 to determine next steps.
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, is being evaluated for the treatment of AML. Mipletamig is designed to redirect the patient’s immune system to destroy leukemic cells and leukemic stem cells expressing CD123, which is overexpressed on leukemic stem cells and AML blasts. Mipletamig 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 cytokine release syndrome by using the CRIS-7-derived CD3 binding pathway, an approach that differentiates Aptevo from competitors.
(Press release, Aptevo Therapeutics, SEP 3, 2026, View Source [SID1234670578])