On March 20, 2025 Aptevo Therapeutics ("Aptevo") (NASDAQ:APVO), a clinical-stage biotechnology company developing novel bispecific immuno-oncology therapeutics based on its proprietary ADAPTIR and ADAPTIR-FLEX platform technologies, reported two additional frontline AML patients have achieved remission* within 30 days of treatment in the Company’s RAINIER dose optimization trial evaluating mipletamig in combination with standard of care for patients unfit for intensive chemotherapy (Press release, Aptevo Therapeutics, MAR 20, 2025, View Source [SID1234651323]). In total, 9 of 10 frontline patients across two trials achieved remission* when receiving the triplet combination of mipletamig + venetoclax + azacitidine (ven/aza). Notably, no CRS has been reported in the RAINIER trial to date.
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The data builds on previously reported favorable outcomes from RAINIER’s Cohort 1 and the completed dose expansion trial where 100% of frontline patients achieved remission. Together with the addition of these interim Cohort 2 results, mipletamig has achieved a compelling overall remission rate of 90% among frontline patients. This outperforms the doublet remission* rate from a venetoclax + azacitidine only study, of 66%. Additionally, the frontline patient triplet therapy CR rate of 70% outperforms the CR rate from a venetoclax + azacitidine only study of 36% (Viale-A Pivotal trial).Thus far, all RAINIER patients who achieved remission remain in remission.
Cohort 2 will include six patients, dosed at the 18mcg level, the same dose used in combination with ven/aza in the completed expansion trial.
Three patients evaluable for efficacy achieved the following outcomes:
Two patients achieved remission withing 30 days of being dosed
One patient progressed after the first cycle and passed away for reasons unrelated to study drugs
Cohort 2 enrollment is nearing completion
"We’re now past the halfway mark in Cohort 2 of the RAINIER trial and are thrilled by the continued, highly favorable remission results," said Dirk Huebner, MD, Chief Medical Officer of Aptevo. " This emerging pattern further supports mipletamig’s impact on treatment outcomes in frontline AML patients who are not fit for intensive chemotherapy and who would otherwise receive ven/aza as the standard of care. One of our primary goals with the RAINIER trial is to demonstrate the contribution of mipletamig’s unique mechanism of action when used in combination with venetoclax and azacitidine. By targeting AML this way, our approach has the potential to improve outcomes, particularly for elderly patients who have limited treatment options."
Mipletamig, a differentiated by design CD3 x CD123 bispecific antibody built on Aptevo’s ADAPTIR platform and driven by a unique CRIS-7 derived binding domain, is being investigated as frontline therapy in combination with venetoclax and azacitidine, the current standard of care for AML patients who are unfit for intensive chemotherapy. These latest results further reinforce mipletamig’s potential as a transformative treatment, supported by impressive efficacy, safety, and tolerability data from two prior clinical trials involving almost 100 patients.
*Remission = complete remission (CR) and, complete remission with blood markers that have not yet recovered (CRi).
About RAINIER
RAINIER, a frontline AML study, is a Phase 1b/2 dose optimization, multi-center, multi-cohort, open label study of up to 39 patients who are being treated across five dose levels ranging from 9 mcg – 140 mcg in combination with venetoclax and azacitidine (ven/aza). Subjects will be adults aged 18 or older, newly diagnosed with AML who are not eligible for intensive induction chemotherapy. Phase 1b consists of 28-day cycles of treatment in five sequential cohorts. Aptevo has partnered with Prometrika (View Source), a premier contract research organization for the trial. RAINIER will be conducted in two parts. First, a Phase 1b dose optimization study in frontline AML patients followed by a Phase 2 study.
Cohort 1 included 3 patients, dosed at the 9mcg level.
All patients achieved remission* within 30 days
Thus far, all patients who achieved remission remain in remission.
One CR patient had no minimal residual disease (MRD-negative status) and was positive for the TP53 genetic mutation, which is generally associated with poor prognosis due to chemotherapy resistance, genetic instability, and overall treatment challenges
About Mipletamig
Aptevo’s wholly owned lead proprietary drug candidate, mipletamig, targeting AML, MDS and other leukemias, 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 a unique CD3 derived from CRIS-7 vs. the CD3 used by other competitors. Mipletamig has received orphan drug designation ("orphan status") for AML according to the Orphan Drug Act. Mipletamig has been evaluated in almost 100 patients over three trials to date. RAINIER, Aptevo’s Phase 1b/2 frontline AML program, was initiated in 3Q24.