New CD40 antibody shrinks metastatic tumors with minimal side effects

A Phase I clinical trial of a novel CD40 agonist antibody (2141-V11) showed tumor shrinkage in half of the treated patients, with two achieving complete remission, by delivering the drug directly into tumors to trigger a systemic immune response.

Why it matters: This marks a major step forward in cancer immunotherapy, offering a safer and more effective approach to treat aggressive metastatic cancers, including melanoma and breast cancer.

Backstory: CD40 antibodies have long shown potential in activating the immune system against cancer but caused severe side effects when administered systemically. In 2018, researchers engineered 2141-V11 to be more potent and administered it intratumorally to reduce toxicity.

Big picture: The trial demonstrates that targeting tumors locally can trigger whole-body immune responses, transforming how immunotherapies might be delivered and potentially improving outcomes for cancers previously resistant to treatment.

The trial:

• Of the trial´s 12 patients, 6 showed tumor reduction and 2 had complete remissions.

• The drug triggered immune activity even in non-injected tumors.

• Tumors transformed into immune-rich structures known as tertiary lymphoid structures (TLS), linked to improved outcomes.

• Ongoing trials with nearly 200 participants are investigating the effectiveness against bladder, prostate, and brain cancers.

• Future studies will also aim to identify biomarkers that can predict which patients will respond to the treatment.