F-star Therapeutics has announced the first patient has been dosed in its Phase 1 trial evaluating FS120, a first-in-class dual-agonist tetravalent bispecific antibody targeting CD137 (4-1BB, TNFRSF9) and OX40 (CD134, TNFRSF4).

The adaptive Phase 1 trial will explore FS120 as a monotherapy in dose escalation including evaluation of PK/PD in patients with advanced cancer. FS120 will also be evaluated in combination with a PD-1 monoclonal antibody with the potential for early demonstration of efficacy in specific tumor subtypes.

FS120 has the potential to show activity in "cold" tumors and improve outcomes of existing immunotherapies by simultaneously agonizing CD137 and OX40. These two receptors are part of the Tumor Necrosis Factor Receptor family ("TNFRSF") and are widely expressed on activated T cells and NK cells in tumors. Many TNFRSF-targeting antibodies require crosslinking via Fcγ receptors (FcγRs) to show activity, but this engagement can limit their clinical activity and lead to significant toxicity. FS120 has been designed to be FcγR-null and instead uses bispecific crosslinking to drive robust receptor clustering and activation, without engaging the FcγR. FS120 preclinical data demonstrated delays in tumor growth, activation and proliferation of CD4+ and CD8+ T cells, and synergies with PD-1 monoclonal antibodies and chemotherapies.

"The initiation of this trial is a significant milestone for F-star as we look to transform the care of those patients with cancer who have limited treatment options. FS120 offers an opportunity to improve upon current treatment paradigms, either as a monotherapy or in combination. We look forward to the results from our FS120 clinical trial as we strive to improve both quality of life and duration of response for patients with these difficult to treat cancers," Louis Kayitalire, CMO of F-star, said.