MP0310

In their BM niche, MM cells adhere to FBs sustaining immune evasion, drug resistance and the undetectable endurance of tumor cells known as minimal residual disease (MRD). Here, we describe the novel bi-specific designed ankyrin repeat protein (DARPin) α-FAPx4-1BB (MP0310) with FAP-dependent 4-1BB agonistic activity. Therefore, α-FAPx4-1BB enhanced both the adhesion of daratumumab-treated NK cells on FBs as well as their activation by improving release of CD107a and perforin, hence MM cell killing via antibody-mediated cell cytotoxicity (ADCC). Interestingly, α-FAPx4-1BB significantly potentiated daratumumab-mediated ADCC in the presence of FBs, suggesting that it may overcome the BM FBs' immunosuppressive effect. Overall, we speculate that treatment with α-FAPx4-1BB may represent a valuable strategy to improve mAb-induced NK cell activity fostering MRD negativity in MM patients through the eradication of latent MRD cells.

P1, N=38, Completed, Molecular Partners AG | Active, not recruiting --> Completed

P1, N=38, Active, not recruiting, Molecular Partners AG | Recruiting --> Active, not recruiting | N=58 --> 38

P1, N=58, Recruiting, Molecular Partners AG | Trial primary completion date: Oct 2021 --> Jul 2022

P1, N=58, Recruiting, Molecular Partners AG | Trial completion date: Apr 2023 --> Dec 2022 | Trial primary completion date: Apr 2021 --> Oct 2021

It provides a rationale for selecting the maximum tested dose, and may help reduce the number of cancer patients receiving sub-therapeutic doses. MP0310 (AMG 506) is currently being evaluated in a Ph1 clinical study.