Status: RAINIER dose optimization trial ongoing
About RAINIER
Aptevo’s RAINIER trial is a multi-center Phase 1b/2 study evaluating mipletamig, a first-in-class CD123 x CD3 bispecific antibody, in combination with venetoclax and azacitidine for newly diagnosed acute myeloid leukemia (AML) patients who are not candidates for intensive chemotherapy.
The study is designed to optimize dosing and confirm that mipletamig can be safely combined with the current standard of care while delivering meaningful clinical benefit.
Highlights
Early results across multiple dose-escalation and optimization cohorts highlight three consistent themes:
- Efficacy – Mipletamig has repeatedly produced more durable remissions in frontline AML, building on encouraging responses seen in earlier studies
- Safety – No dose-limiting toxicities or cytokine release syndrome have been observed to date, underscoring the differentiated safety profile enabled by Aptevo’s uniquely designed CRIS-7-derived CD3 binding domain
- Combinability – Mipletamig has demonstrated its ability to integrate with the venetoclax/azacitidine backbone, maintaining tolerability even at the highest dose levels studied
Outcomes to date reinforce mipletamig’s potential to become an important new component of frontline AML therapy and exemplify Aptevo’s mission to deliver safer, more effective immuno-oncology treatments to the market.
For the latest mipletamig news click here.
Why we are targeting CD123
Overexpression of CD123 is a mark of many forms of leukemia. Aptevo’s lead proprietary drug candidate, mipletamig is a bispecific CD3xCD123 ADAPTIR molecule that is designed to redirect the patients’ immune system to destroy leukemia cells expressing the surface target antigen CD123. This antibody-like recombinant protein therapeutic is designed to simultaneously engage both leukemia cells and T cells of the immune system to trigger the destruction of leukemia cells. Mipletamig has been designed with a unique CD3 binding domain to reduce the likelihood and severity of cytokine release syndrome (CRS). Mipletamig has received orphan drug designation for AML according to the Orphan Drug Act.
The Molecule
Potential advantages of Mipletamig include:
Broad Utility: The tumor-associated antigen CD123 is expressed on several hematological malignancies including acute myeloid leukemia, acute lymphoblastic leukemia, hairy cell leukemia, myelodysplastic syndrome, and blastic plasmacytoid dendritic cell neoplasm, which all have significant unmet needs for safe and effective new therapies.
Reduced Toxicity: The unique CD3 binding domain has high potency tumor killing while inducing a reduced cytokine release profile in vitro. This approach has been shown clinically to provide a safer and more tolerable treatment for AML patients.