714TiP - A phase Ia/Ib, first-in-human, dose-escalation study evaluating the safety, tolerability, and efficacy of IOS-1002, a LILRB1, LILRB2, and KIR3DL1 targeting HLA-derived fusion protein administered alone or in combination with a PD-1 antibody in patients with advanced solid tumors

Background

IOS-1002 is a recombinant homodimer of the human leukocyte antigen B57 free heavy chain linked to a human IgG4 Fc backbone associated with human β2 microglobulin. The binding of IOS-1002 to LILRB1, LILRB2, and KIR3DL1 receptors blocks the interaction with tumor-expressed ligands such as HLA-G. Through this mechanism, IOS-1002 enhances the immune response of diverse sets of both innate and adaptive immune cells and leads to tumor cell killing. The anti-tumor effect is enhanced by combining IOS-1002 with a PD-1 check point blockade inhibitor in pre-clinical models The present study evaluates the safety, tolerability, pharmacokinetics, efficacy, immunogenicity, and pharmacodynamics of IOS-1002 as monotherapy and as combination therapy with a PD-1 monoclonal antibody in subjects with advanced solid tumors.

Trial design

The phase 1a/1b trial is being conducted at five sites in Australia and has started enrollment as of March 2023. The trial is separated in 2 parts: Dose Escalation (A): Subjects are enrolled into 10, 30, 100, 300, 800, and 1200 mg dose levels sequentially and treated with IOS-1002 Q2W IV. Guided by the dose-limiting toxicities (DLTs) observed, an accelerated dose titration design is used for the first 3 dose levels followed by a 3+3 dose escalation. The DLT period is defined as 4 weeks following cycle 1 day 1 infusion. Once monotherapy reaches the 800 mg dose level, the combination therapy with a 3 + 3 dose escalation starts at a dose of 300 mg Q2W for IOS-1002 in combination with a PD-1 mAb at approved dose and schedule. The IOS-1002 RP2D or MAD as identified for monotherapy and PD-1 combination will then be used in the dose expansion part. Dose Expansion (B): Following the toxicity and activity profile observed in part A, a tumor-specific cohort expansion study in up to 6 potential disease entities with 20 patients per cohort will be initiated, 3 as IOS-1002 monotherapy and 3 as IOS-1002 + PD-1 combination. Depending on the disease entity and line of treatment, the PD-1 cohort will include PD-1 naïve, pre-exposed and refractory patients, respectively.

Clinical trial identification

Clinical Trials Registry Number: NCT05763004.

Editorial acknowledgement

Legal entity responsible for the study

ImmunOs Therapeutics AG.

Funding

ImmunOs Therapeutics AG.

Disclosure

C. Berger, M. Gualandi, A. Rafiei, C. Renner: Financial Interests, Personal, Full or part-time Employment: ImmunOs Therapeutics. All other authors have declared no conflicts of interest.