GEN1042

P1, N=30, Recruiting, Genmab | Trial completion date: Oct 2027 --> Feb 2027

P1/2, N=1287, Recruiting, Genmab | N=647 --> 1287 | Trial primary completion date: Oct 2025 --> Jul 2025

P1, N=30, Recruiting, Genmab | Not yet recruiting --> Recruiting

Preclinical data shows enhanced priming and anti-tumor activity inclusive of T cell proliferation and effector functions. Furthermore, monotherapy and combination data from our FIH, open-label, phase I/II trial (NCT04083599) reveal a manageable safety profile, clinical activity, and pharmacodynamics consistent with the mechanism of action.

These data suggest that, in addition to enhancing T-cell effector functions during T cell priming, GEN1042 can amplify the magnitude of the immune response in combination with PD-1 blockade by re-establishing the functional activity of dysfunctional T cells. GEN1042 is currently being evaluated in patients with advanced solid tumors in a phase 1/2 clinical trial (NCT04083599).

DuoBody-CD40×4-1BB is capable of enhancing antitumor immunity by modulating DC and T-cell functions and shows biological activity in patients with advanced solid tumors. These findings demonstrate that targeting of these two pathways with an Fc-inert bispecific antibody may be an efficacious approach to (re)activate tumor-specific immunity and support the clinical investigation of DuoBody-CD40×4-1BB for the treatment of cancer.

In conclusion, GEN1042 showed biologic and preliminary antitumor activity with a manageable safety profile in patients with advanced solid tumors. Expansion cohorts are currently enrolling, including evaluation of GEN1042 in combination with PD-1 inhibitors.

Preliminary findings from a first-in-human phase I/II trial of GEN1042, a bispecific antibody that simultaneously targets CD40 and 4-1BB on immune cells, suggest that this drug is well tolerated and active in patients with advanced solid tumors.

Conclusions DuoBody-CD40×4-1BB demonstrated biologic and early antitumor activity with a favorable safety profile in patients with advanced solid tumors. Expansion cohorts, including combination therapy with PD-1 inhibitors, are currently enrolling.

Thereby, DuoBody-CD40×4-1BB provides a unique combination of priming and enhancing existing anti-tumor immunity. DuoBody-CD40×4-1BB is currently being evaluated in patients with advanced solid tumors in a first-in-human trial (NCT04083599).