Dr Oberstein on the Rationale for Evaluating the PD-1/IL-15 Fusion Protein SAR445877 in MSS CRC

“Can we overcome some of the real barriers to immune response in cold tumors like CRC by using this combination strategy?”

Paul E. Oberstein, MD, an associate professor in the Department of Medicine at the New York University (NYU) Grossman School of Medicine, service chief of the Gastrointestinal Medical Oncology Program, and assistant director of the Pancreatic Cancer Center at NYU Langone Health’s Perlmutter Cancer Center, discussed the rationale behind the investigational anti–PD-1/IL-15 fusion protein SAR445877 and the unmet need for effective immunotherapy in microsatellite-stable (MSS) colorectal cancer (CRC).

SAR445877 reflects exciting, out-of-the-box thinking, Oberstein said. The agent is a fusion molecule that takes an anti–PD-1 antibody and fuses it to a modified interleukin-15 (IL-15) cytokine, he explained. The concept is to stimulate the immune system to fight tumors in 2 different ways: by blocking the PD-1 checkpoint, which activates T cells; and by using a cytokine, IL-15, which directly stimulates the immune system, according to Oberstein. The goal is to determine whether this combined mechanism of action can overcome some of the barriers to immune response in immunologically cold tumors, such as CRC, he noted.

Immunotherapy has revolutionized cancer care, generating significant benefits in certain tumor types, Oberstein said. However, for MSS CRC, immunotherapy appears to have little or no therapeutic role in the traditional form in which it has been tested, he noted.

As such, there is a need to develop effective immunotherapy agents for this large cohort of patients with MSS CRC, Oberstein said. Many gastrointestinal (GI) oncology researchers have approached this in different ways, and several trials are ongoing, generating excitement in the GI cancer field, he added. SAR445877 is trying to fit that niche and provide an effective immunotherapy option for patients with advanced CRC that is otherwise not responsive to immune-based treatment, Oberstein concluded.