A Phase 1b Study to Evaluate Safety and Efficacy of IBI188 in Combination with Azacitidine (AZA) As a First-Line Treatment in Subjects with Newly Diagnosed Higher Risk Myelodysplastic Syndrome

Background: IBI188 is a recombinant fully human IgG4 monoclonal antibody targeting CD47, an antiphagocytic ('don't eat me') signal present on cancer cells. Blockage of this innate immune checkpoint, IBI188 enhances tumor cell phagocytosis. The study reported updated results from a phase 1b study (NCT04485065) that evaluated safety and efficacy of IBI188 in combination with AZA as a first-line treatment in subjects with newly diagnosed higher-risk myelodysplastic syndrome (MDS).

Methods: IBI188 plus AZA was given to untreated intermediate to very high risk (IPSS-R > 3.5) MDS patients. An IBI188 priming/intrapatient dose escalation regimen (0.1-30 mg/kg QW) was used. AZA was dosed 75mg/m² days 1-7 Q4W. Patients received IBI188 until disease progression, unacceptable toxicity, or withdraw ICF. The primary endpoint was to evaluate the safety and tolerability of IBI188 in combination with AZA. Efficacy was assessed by IWG 2006 (MDS).

Results: Ninety-three patients (pts) were enrolled (median age: 59.0 years, 58 [62.4%] males). 72% pts were high to very high risk by IPSS-R. With a median follow-up of 9.2 mos (range: 0.1-21.0 mos), the most common IBI188-related AEs (≥30%) were platelet count decreased (49.5%), anaemia (44.1%), blood bilirubin increased (36.6%), neutrophil count decreased (36.6%), white blood cell count decreased (36.6%), and haemolysis (34.4%). Nine pts (9.7%) discontinued treatment due to IBI188-related AE. For 45 evaluable pts with ≥ 6 mos follow-up, 37/45 (82.2%) pts had an objective response with 14 pts (31.1%) achieving a complete response (CR), 16 (35.6%) with marrow CR (9/16 also had hematologic improvement (HI)), and 7 (15.6%) with HI alone. The median duration of response was 12.0 months (95%CI, 6.5-NC). A randomized phase 3 MDS trial is planned. Additional patients/analyses will be updated.

Conclusions: IBI188 in combination with azacitidine demonstrated promising efficacy, and a manageable safety profile as a first-line treatment in subjects with newly diagnosed higher risk myelodysplastic syndrome.

Keywords: Myelodysplastic syndrome, Immune therapy, CD47, IBI188

Clinical trial information: NCT04485065

Zhou:Innovent Biologics Inc.: Current Employment. Wang:Innovent Biologics Inc.: Current Employment. Chen:Innovent Biologics Inc.: Current Employment. Niu:Innovent Biologics Inc.: Current Employment. Chen:Innovent Biologics Inc.: Current Employment.