Activating Inducible T-cell Costimulator Yields Antitumor Activity Alone and in Combination with Anti-PD-1 Checkpoint...

Area of Science:

• Immunology
• Oncology
• Pharmacology

Background:

• Monoclonal antibodies (mAbs) targeting costimulatory receptors aim to enhance anti-cancer immunity.
• Despite interest, translating preclinical success of costimulatory receptor signaling to clinical benefit remains a challenge.
• Inducible T-cell Costimulator (ICOS) is crucial for effective T-cell responses and anti-tumor immunity.

Purpose of the Study:

• To evaluate the anti-tumor potential of the novel anti-ICOS mAb, feladilimab, which induces ICOS signaling.
• To assess feladilimab's efficacy as a monotherapy and in combination with PD-1 blockade.
• To present initial clinical data from a Phase I trial investigating feladilimab in advanced solid tumors.

Main Methods:

• Utilized a novel clinical-stage anti-ICOS IgG4 mAb (feladilimab) in nonclinical models (mouse and humanized tumors).
• Evaluated feladilimab's ability to induce ICOS signaling and stimulate anti-tumor T cells.
• Conducted a first-in-human Phase I clinical trial (INDUCE-1) assessing feladilimab with or without pembrolizumab in advanced solid tumors.

Main Results:

• Demonstrated consistent ICOS expression across various cancers, with induction stimulating anti-tumor T cells.
• Showed that feladilimab, alone and combined with a PD-1 inhibitor, induced significant anti-tumor activity in preclinical models.
• Presented case studies from the Phase I trial indicating preliminary clinical benefit in patients with advanced solid tumors.

Conclusions:

• Antibody-mediated ICOS costimulation with feladilimab shows promise for cancer therapy.
• Combination therapy with PD-1 blockade may enhance anti-tumor responses.
• Further validation through randomized trials is necessary to confirm clinical efficacy and identify optimal patient populations.