BI-836858

Summary

BI‑836858 is a fully human, Fc‑engineered monoclonal antibody that targets CD33, a surface antigen expressed on most acute myeloid leukaemia (AML) cells and on lower‑risk myelodysplastic syndrome (MDS) clones. It is being investigated as an immunotherapy to trigger immune‑mediated killing of CD33‑positive blasts, either alone or in combination with agents such as decitabine, the polo‑like‑kinase inhibitor volasertib, or an IL‑2‑based cytokine fusion.

Mechanism of Action

BI‑836858 binds the myeloid differentiation antigen CD33 on leukemic blasts. Its engineered Fc region has enhanced affinity for the activating FcγRIIIA (CD16) receptor on natural‑killer (NK) cells, promoting antibody‑dependent cellular cytotoxicity (ADCC). By directing NK‑cell cytotoxic granules to CD33‑positive cells, the antibody mediates target cell lysis while sparing NK‑cell viability. Pre‑clinical data suggest that combining the antibody with agents that increase tumour susceptibility (e.g., volasertib) can further augment ADCC.

What the Research Shows

Early‑phase clinical work has examined BI‑836858 in several settings. A phase I trial in relapsed AML evaluated safety, pharmacokinetics and preliminary activity of the IV antibody. A phase I/II study combined BI‑836858 with decitabine, establishing a maximum tolerated dose and reporting tolerable safety alongside modest efficacy signals. A separate phase I/II dose‑escalation and randomised trial investigated the agent in low‑ or intermediate‑1‑risk MDS. Pre‑clinical work showed that volasertib, a polo‑like‑kinase inhibitor, does not impair NK‑cell function and enhances BI‑836858‑mediated ADCC in patient samples. A novel combination with the ECM‑anchored IL‑2 fusion protein F16IL2 in post‑transplant AML relapse demonstrated manageable infusion‑related reactions, dose‑limiting pulmonary edema or graft‑versus‑host disease in a few patients, and objective responses at higher dose levels. Collectively, these studies provide proof‑of‑concept for CD33‑directed ADCC and suggest potential synergy with other agents, but data remain limited to early‑stage trials.

Reported Benefits

Evidence from phase I/I‑II trials indicates that BI‑836858 can engage NK cells to produce ADCC against CD33‑positive blasts, with a safety profile that is generally manageable (mostly low‑grade infusion reactions). Early signals of clinical activity have been observed in relapsed AML, post‑transplant AML relapse, and low‑risk MDS, especially when combined with decitabine or IL‑2‑based cytokine targeting. Pre‑clinical data suggest that combining the antibody with volasertib may increase cytotoxic effectiveness without harming NK‑cell function.

Limitations of the Evidence

All data come from early‑phase, small‑sample studies; no randomized controlled trials have been completed, limiting confidence in efficacy. Reported responses are modest and observed only in subsets of patients receiving higher dose levels. Dose‑limiting toxicities such as pulmonary edema and graft‑versus‑host disease have been noted, and long‑term safety and durability of responses remain unknown. The benefit of combining BI‑836858 with other agents is based on limited patient numbers and pre‑clinical observations.

Safety Considerations

Phase I/I‑II studies have reported infusion‑related adverse events including fever, chills and transient reactions, typically grade 1‑2. In the BI‑836858/F16IL2 combination, one instance each of pulmonary edema and graft‑versus‑host disease were identified as dose‑limiting toxicities. NK‑cell viability appears preserved, even when patients receive the polo‑like‑kinase inhibitor volasertib. Overall, the safety profile is considered acceptable for early‑stage investigation, but serious toxicities have been observed and require monitoring in further trials.

How It Is Administered

BI‑836858 is administered intravenously. Monotherapy dose ranges in early trials have spanned 10–40 mg IV, often given on a weekly or bi‑weekly schedule. In combination protocols, the antibody is infused a few days after the partner agent (e.g., 2 days after F16IL2 or alongside decitabine). Formulation details are limited to its presentation as a sterile antibody solution for IV infusion.

Routes of Administration

Goals & Uses

• Combination therapy in AMLOncologyLow
• Treatment of relapsed/refractory acute myeloid leukemia (AML)OncologyLow
• Treatment of myelodysplastic syndromes (MDS)OncologyLow

Contraindications

• Hypersensitivity to BI-836858 or excipientsAllergy/ImmunologyHigh
• Severe uncontrolled infectionInfectionHigh

Adverse Effects

• ThrombocytopeniaHematologicCommonLow platelet count
• Febrile neutropeniaHematologic/InfectiousUncommon
• NeutropeniaHematologicCommonLow neutrophil count
• FatigueGeneralCommonLow energy or tiredness
• Infusion-related reactionsHypersensitivityCommon

Drug Interactions

• Live vaccinesHigh
• CytarabineModerate

Population Constraints

• Pediatric patientsAgeRelative
• Pregnant or breastfeeding womenReproductiveRelative
• Severe hepatic impairmentOrgan ImpairmentRelative

Regulatory Status

• European UnionInvestigationalEvaluated in European clinical trial sites; no EMA approval granted.
• United StatesInvestigationalInvestigated under IND; no FDA approval granted as of knowledge cutoff.

BI-836858 has not received regulatory approval in any jurisdiction as of the knowledge cutoff. It has been evaluated in Phase I/II clinical trials (e.g., NCT02240706 in AML/MDS). Development status beyond early-phase trials is uncertain.

Evidence & Sources

• Polo-like kinase inhibitor volasertib marginally enhances the efficacy of the novel Fc-engineered anti-CD33 antibody BI 836858 in acute myeloid leukemia
  Journal ArticleLowGopalakrishnan B, et al.2018-01-01T00:00:00.000000Z
• An open-label, phase I/II trial to determine the maximum tolerated dose and investigate safety, pharmacokinetics and efficacy of BI 836858, an unconjugated anti-CD33 monoclonal antibody, in combination with decitabine in patients with acute myeloid leukemia
  Journal ArticleModerateFiedler W, et al.2022-01-01T00:00:00.000000Z
• A phase I/II multicenter, open-label, dose escalation and randomized trial of BI 836858 in patients with low- or intermediate-1-risk myelodysplastic syndrome
  Journal ArticleModerateKomrokji RS, et al.2022-01-01T00:00:00.000000Z
• A phase I study of the fully human, fragment crystallizable-engineered, anti-CD-33 monoclonal antibody BI 836858 in patients with previously-treated acute myeloid leukemia
  Journal ArticleModerateVasu S, et al.2022-01-01T00:00:00.000000Z
• Using stroma-anchoring cytokines to augment ADCC: a phase 1 trial of F16IL2 and BI 836858 for posttransplant AML relapse
  Journal ArticleModerateBerdel AF, et al.2022-01-01T00:00:00.000000Z
• Investigational CD33-targeted therapeutics for acute myeloid leukemia
  Journal ArticleModerateWalter RB2018-01-01T00:00:00.000000Z

Frequently Asked Questions