Combination immunotherapy: a road map

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Cancer immunotherapy, particularly monoclonal antibodies targeting the PD-1/PD-L1 pathway, has significantly advanced cancer treatment.
• Despite successes, many patients do not respond to PD-1/PD-L1 pathway inhibitors alone, necessitating combination strategies.
• Combining PD-1/PD-L1 inhibitors with other agents may enhance clinical benefits, as suggested by early studies in melanoma and NSCLC.

Purpose of the Study:

• To address progress and challenges in cancer combination immunotherapy.
• To identify and prioritize promising combination strategies involving PD-1 pathway inhibitors.
• To provide an overview of current evidence and discuss key developmental issues.

Main Methods:

• Convening a Combination Immunotherapy Task Force by the Society for Immunotherapy of Cancer (SITC).
• Reviewing current evidence for PD-1 pathway inhibitors as a backbone in combination therapies.
• Discussing critical aspects of combination immunotherapy development, including preclinical modeling, safety, trial design, and endpoints.

Main Results:

• PD-1 pathway inhibitors show potential as a backbone for combination immunotherapy due to clinical benefits and tolerable side effects.
• The SITC task force identified key challenges in developing combination immunotherapies.
• The manuscript summarizes the current status and future challenges for combination immunotherapy.

Conclusions:

• Combination immunotherapy holds significant promise for improving cancer treatment outcomes.
• Addressing challenges in preclinical modeling, patient safety, and clinical trial design is crucial for successful development.
• Further research and strategic development are needed to optimize combination immunotherapy approaches for a wider patient population.