Aptevo Reports Strong Remission Data in Frontline AML Trial as RAINIER Study Advances Toward Phase 2

Aptevo Therapeutics has reported updated clinical results from its ongoing Phase 1b RAINIER trial evaluating mipletamig in combination with venetoclax and azacitidine in frontline acute myeloid leukemia (AML). The company said the study remains on track for completion in 2026 and for selection of a recommended Phase 2 dose later this year.¹

According to the company, data from 31 evaluable frontline AML patients demonstrated an 87% clinical benefit rate and an 81% composite remission rate, including complete remission (CR) and complete remission with incomplete hematologic recovery (CRi). The dataset included 27 patients treated in the ongoing RAINIER trial through Cohort 5 and four patients from a prior dose-expansion study.

The updated findings suggest the investigational immunotherapy regimen may compare favorably with currently established frontline AML treatment approaches for patients ineligible for intensive induction chemotherapy.

Clinical Activity Continues Across Expanding Dataset

Mipletamig is being developed as a CD123-targeting bispecific antibody designed to redirect T cells against leukemic cells and leukemic stem cells. CD123 remains an attractive therapeutic target in AML because of its overexpression on AML blasts and stem cell populations associated with disease persistence and relapse.

Among the evaluable patients treated to date, Aptevo reported that 65% achieved complete remission, while 55% of patients achieving CR or CRi also reached measurable residual disease (MRD)-negative status, a biomarker often associated with deeper and potentially more durable responses.

The company also noted that 36% of responding patients carried TP53 mutations, a high-risk genomic feature linked to poor prognosis and resistance to standard therapies in AML.

Importantly, six patients proceeded to allogeneic stem cell transplantation following treatment. In older or medically unfit AML populations, successful transition to transplant is relatively uncommon but remains one of the few potentially curative treatment pathways.

“Our results demonstrate a consistent pattern of clinical activity and favorable safety across patients treated to date,” said Dirk Huebner, MD, chief medical officer of Aptevo Therapeutics, in the company announcement.¹

Safety Profile Remains Favorable

Aptevo stated that no cytokine release syndrome (CRS) events had been reported to date, a notable finding for a T-cell-engaging bispecific therapy. CRS remains a major safety consideration across the bispecific antibody landscape, particularly in hematologic malignancies.

The company said mipletamig incorporates a proprietary CD3-binding approach intended to reduce the likelihood and severity of CRS while maintaining anti-leukemic activity.

The RAINIER study has now progressed into its final dose-optimization stage, including enrollment into Cohorts 6 and 7, representing the highest mipletamig dose levels evaluated so far. Additional patients will also be enrolled at selected dose levels to support Phase 2 dose selection and planned regulatory discussions.

“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, in the release.¹

AML Treatment Landscape Continues to Evolve

The frontline AML treatment landscape has shifted significantly following the introduction of venetoclax-based combination regimens for older or chemotherapy-ineligible patients. In the pivotal Phase 3 VIALE-A trial, venetoclax plus azacitidine demonstrated a composite CR/CRi rate of 66.4% and helped establish the regimen as a standard of care in this patient population.²

However, outcomes remain suboptimal for many high-risk patients, particularly those with adverse molecular features such as TP53 mutations. As a result, developers continue exploring novel immunotherapy approaches, including bispecific antibodies, antibody-drug conjugates, and cell therapies designed to improve response durability and long-term survival.³ CD123 has emerged as a particularly important therapeutic target in AML because of its high expression on leukemic blasts and stem cells associated with disease persistence and relapse.⁴ Aptevo’s mipletamig program represents one of several CD123-targeted strategies currently under investigation in AML, reflecting continued industry interest in immune-engaging approaches for difficult-to-treat hematologic malignancies.

References

1. Aptevo reports 87% clinical benefit and 81% remission in 31 evaluable frontline AML patients through Cohort 5, substantially outperforming benchmark; RAINIER on track for 2026 completion and Phase 2 dose selection. (6 May 2026). ACCESS Newswire. https://www.accessnewswire.com/newsroom/en/healthcare-and-pharmaceutical/aptevo-reports-87-clinical-benefit-and-81-remission-in-31-evaluable-f-1164140
   
2. DiNardo, C. D., Jonas, B. A., Pullarkat, V., Thirman, M. J., Garcia, J. S., Wei, A. H., ... & Kantarjian, H. M. (2020 Aug 12). Azacitidine and venetoclax in previously untreated acute myeloid leukemia. New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2012971
   
3. Short, N. J., Konopleva, M., Kadia, T. M., Borthakur, G., Ravandi, F., & DiNardo, C. D. (2020 Apr 1). Advances in the treatment of acute myeloid leukemia: New drugs and new challenges. Cancer Discovery. https://doi.org/10.1158/2159-8290.CD-19-1011
   
4. Testa, U., Pelosi, E., & Castelli, G. (2019 Aug 14). CD123 as a therapeutic target in the treatment of hematological malignancies. Cancers. https://doi.org/10.3390/cancers11091358