Mipletamig Regimen Yields Clinical Benefit in Frontline AML Trial

Combining mipletamig with venetoclax (Venclexta) and azacitidine (Vidaza) produced clinical benefits and remissions in most patients with frontline acute myeloid leukemia (AML), according to a press release on updated findings from the phase 1b/2 RAINIER trial (NCT06634394).¹

Among 31 evaluable patients, including 27 from cohorts 5 and 4 from the completed dose-expansion trial, the mipletamig combination produced a clinical benefit rate (CBR) of 87% whiles showing broad anti-leukemia activity and blast reductions across response categories. Additionally, 81% of patients experienced a complete response (CR) or CR with incomplete hematologic recovery (CRi), and 65% had a CR. Data also showed that 36% of patients with a response had TP53-mutated disease, while 6 proceeded to allogeneic stem cell transplant thus far in the trial.

The efficacy results from the RAINIER trial appear to compare favorably with historical benchmarks established in the phase 3 VIALLE-A trial (NCT02993523), in which azacitidine plus venetoclax yielded a composite CR/CRi rate of 66.4% and a CR rate of 36.7% among patients with AML who were ineligible to undergo intensive induction chemotherapy.²

Safety findings showed that no patients experienced cytokine release syndrome (CRS) to date.

With the completion of cohort 5, dosing has proceeded to all previously evaluated mipletamig dose levels. The trial’s final stage includes 2 final dose-level cohorts—cohorts 6 and 7—representing the highest evaluated doses of mipletamig. The final stage also includes 2 other groups of 6 additional patients who will be assigned to receive select dose levels of mipletamig; the first patient will enroll concurrently on cohort 6.

Investigators are on track to finish the phase 1b dose-optimization portion of the trial, determine the recommended phase 2 dose, and complete the planned phase 2 regulatory interaction sometime in 2026.

“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,” Jeff Lamothe, president and chief executive officer at Aptevo Therapeutics, the developer of mipletamig, stated in the press release.¹ “The data are 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.”

Investigators of the dose-optimization, multi-center, multi-cohort phase 1b/2 RAINIER trial are assessing the mipletamig-based regimen among patients with newly diagnosed AML who are eligible to receive intensive induction chemotherapy. The phase 1b dose-optimization portion of the trial consisted of 28-day cycles of treatment across different sequential cohorts.

The primary end point was the safety, tolerability, and maximum tolerated dose of increasing doses of mipletamig in combination with venetoclax and azacitidine.³ The efficacy of the combination based on CR rate was a secondary end point.

Patients 18 years and older with CD123-positive AML per local flow cytometry or immunohistochemistry were eligible for enrollment on the study. Having ineligibility for induction therapy was another requirement for study entry, which was based on meeting at least 1 of the following criteria: having an ECOG performance status of 2 or 3, cardiac disorders, and pulmonary disorders, among others.

“Our results demonstrate a consistent pattern of clinical activity and favorable safety across patients treated to date. As dose selection progresses, the focus is on identifying a phase 2 dose that is supported by a complete and well-characterized dataset,” Dirk Huebner, MD, chief medical officer at Aptevo Therapeutics, concluded.¹

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. News release. Aptevo Therapeutics Inc. May 6, 2026. Accessed May 6, 2026. https://tinyurl.com/ycyvahnu
2. DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383(7):617-629. doi:10.1056/NEJMoa2012971
3. APVO436 phase 1b/​2 study in patients with newly diagnosed AML. ClinicalTrials.gov. Updated May 11, 2025. Accessed May 6, 2026. https://tinyurl.com/yfcuhzb9