Mipletamig/SOC Achieved Complete Remission Rates in Front-Line AML

Results from the RAINIER trial showed that mipletamig, venetoclax, and azacitidine achieved a complete remission rate of 90% in patients with AML.

Mipletamig, a CD3 by CD19123 bispecific antibody, plus standard-of-care venetoclax (Venclexta) and azacitidine elicited complete remission within 30 days of treatment in the front-line setting for patients with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy, according to a press release from the developer, Aptevo.¹

The drug combination elicited an overall remission rate of 90% (n = 9/10) in patients with AML who received treatment in a first-line setting across 2 cohorts, and no cytokine release syndrome (CRS) has been identified.

Results from the dose optimization, multi-cohort phase 1b/2 RAINIER trial (NCT03647800) that evaluated possible dosages of mipletamig and located the recommended phase 2 dose (RP2D) in the part 1b section and evaluated the safety and tolerability of the RP2D in the part 2 section.² Previous results showed a 100% remission rate for patients in cohort 1 of the study.

“We’re now past the halfway mark in cohort 2 of the RAINIER trial and are thrilled by the continued, highly favorable remission results,” Dirk Huebner, MD, chief medical officer of Aptevo, stated in the press release.¹ “This emerging pattern further supports mipletamig’s impact on treatment outcomes in frontline AML for patients who are not fit for intensive chemotherapy and who would otherwise receive [venetoclax and azacitidine] 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.”

When compared with the baseline therapy of venetoclax plus azacitidine, which elicited a remission rate of 66%, the triplet with mipletamig demonstrated favorable outcomes; the triplet also demonstrated a complete remission rate of 70% compared with 36% from the doublet therapy in the VIALE-A trial (NCT02993523).³

In the dose-escalation phase, eligible patients were 18 years or older with histologically confirmed relapsed/refractory AML ineligible for intensive chemotherapy or allogenic transplant, or relapsed/refractory myelodysplastic syndrome (MDS) who failed on a prior hypomethylating agent. Additionally, patients had an ECOG performance status from 0 to 2, a life expectancy longer than 2 months, adequate liver test parameters, and willingness to use adequate contraception during and 2 months after study drug administration. Exclusion criteria include any central nervous system disease, history of seizures, prior anti-CD123 therapy, acute promyelocytic leukemia, and any other active systemic malignancies.

RAINIER enrolled a total of 39 patients who were treated across 5 dose levels of mipletamig ranging from 9 mcg to 140 mcg; cohort 1 enrolled a total of 3 patients who received 9 mcg.

In the dose expansion phase, patients in cohort 1 had to be fit with primary or secondary AML in their first or second relapse with complete remission achieved less than 1 year ago; patients in cohort 2 had poor prognosis but were fit with primary or secondary AML and treatment-naïve or in first relapse, and those in relapse were only permitted to have relapsed after induction or consolidation therapy for AML.

Primary end points were the maximum tolerated dose in the dose escalation phase and safety in the dose expansion phase. Secondary end points include frequency and severity of adverse effects, maximum serum drug concentration, elimination of half-life, and pharmacodynamics in the dose escalation part; in the dose expansion part, they were efficacy and incidence of complete remission, the incidence of patients who achieved MRD-negative complete remission, the incidence of patients who undergo hematopoietic stem cell transplant post protocol therapy, and leukemia-free survival.

In cohort 1, all patients achieved complete remission within 30 days and have remained in remission since; one patient who achieved complete remission was minimal residual disease-negative and had the TP53 mutation.

Cohort 2 of the RAINIER trial is currently enrolling patients and will include a total of 6 patients who receive 18 mcg of mipletamig. Of the 3 patients evaluable for efficacy in cohort 2, two achieved remission within 30 days of dosing and 1 progressed after the first cycle and passed away due to reasons non-related to study treatment.

References

1. RAINIER trial data update: two additional AML patients achieve remission within 30 days of treatment. News release. Aptevo. March 20, 2025. Accessed March 24, 2025. https://tinyurl.com/bdzchfv4
2. Study of APVO436 in patients with AML or MDS. ClinicalTrials.gov. Updated February 10, 2022. Accessed March 24, 2025. https://tinyurl.com/4uesf4py
3. 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