RAINIER Data Highlight Activity of Mipletamig Triplet in Frontline AML

Mipletamig (formerly APVO436) combined with venetoclax (Venclexta) and azacitidine (Vidaza) has demonstrated encouraging early efficacy and favorable safety in patients with newly diagnosed acute myeloid leukemia (AML) who are unfit for intensive induction chemotherapy, according to an update from the phase 1b/2 RAINIER trial (NCT06634394).¹

Across 31 evaluable patients, treatment with the triplet yielded an 87% clinical benefit rate and an 81% complete or complete with incomplete hematologic recovery (CR/CRi) remission rate. The CR rate alone was 65%—findings that compare favorably against the 66.4% composite CR/CRi rate and 37% CR rate reported in the intent-to-treat population of the phase 3 VIALE-A trial (NCT02993523),² which established venetoclax plus azacitidine as a standard of care in older or unfit patients with newly diagnosed AML ineligible for intensive induction chemotherapy.

The updated dataset includes 27 patients enrolled in RAINIER through the completion of cohort 5, plus 4 patients treated at an earlier dose level in a previously completed dose-expansion trial. No cytokine release syndrome (CRS) was observed in any patient in the RAINIER trial to date.

"Our results demonstrate a consistent pattern of clinical activity and favorable safety across patients treated to date," Dirk Huebner, MD, chief medical officer of Aptevo Therapeutics, stated in a news release.¹ "As dose selection progresses, the focus is on identifying a [p]hase 2 dose that is supported by a complete and well-characterized dataset."

Mipletamig: Mechanism of Action

Mipletamig is an investigational CD123 × CD3 bispecific antibody-like recombinant protein designed to redirect T cells of the immune system toward CD123-expressing leukemic cells and leukemic stem cells. CD123 is overexpressed on AML blasts and leukemic stem cells, making it a relevant therapeutic target in this disease. The agent employs a CRIS-7–derived CD3 binding domain, a design strategy intended to reduce the incidence and severity of CRS relative to other bispecific T-cell engager platforms.

RAINIER: Clinical Context and Dose Optimization Progress

RAINIER is a multicenter, open-label, multi-cohort phase 1b/2 dose-optimization study enrolling adults aged 18 years or older with newly diagnosed AML who are ineligible for intensive induction chemotherapy.³ The phase 1b portion consists of 28-day treatment cycles across sequential dose cohorts.

The VIALE-A trial established venetoclax plus azacitidine as a standard of care in patients with AML ineligible for intensive chemotherapy. The triplet approach under investigation in RAINIER adds mipletamig to this standard backbone with the goal of enhancing depth and durability of response without materially increasing toxicity, as assessed by the absence of dose-limiting toxicities and CRS to date.

With cohort 5 complete, the trial has entered its final stage of dose optimization. Two additional cohorts—cohorts 6 and 7—representing the highest mipletamig dose levels evaluated in RAINIER, are now being assessed. Enrollment in cohort 6 is nearing completion. Concurrently, 2 groups of 6 patients each will be enrolled at selected dose levels from earlier cohorts to complete the dataset required for recommended phase 2 dose (RP2D) selection.

Phase 2 dose selection will be based on the complete dataset from phase 1b, after which the sponsor plans to advance mipletamig into a phase 2 study using the same triplet combination. The sponsor anticipates completing the phase 1b portion and initiating the planned regulatory interaction for the phase 2 study before the end of 2026.

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. May 6, 2026. Accessed May 11, 2026. https://tinyurl.com/yvc8k7su

2. DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Eng 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 11, 2026. https://clinicaltrials.gov/study/NCT06634394