Intratumoral delivery of PD-1/PD-L1 and CTLA-4 inhibitors for recurrent/refractory solid tumors: a proof-of-concept...

Area of Science:

• Oncology
• Immunotherapy
• Drug Delivery

Background:

• Immune checkpoint inhibitors (ICIs) are a cornerstone of cancer immunotherapy but face challenges with patient resistance and relapse.
• Combination therapy offers a promising strategy to overcome ICI limitations by targeting different aspects of the cancer-immunity cycle.
• Adverse events associated with combination therapies necessitate innovative approaches to improve safety and efficacy.

Purpose of the Study:

• To evaluate the efficacy and safety of combining PD-1/PD-L1 and CTLA-4 inhibitors using an intratumoral drug delivery strategy.
• To assess the potential of this approach in treating recurrent/refractory (R/R) advanced solid tumors.
• To explore the impact of reduced dosage and localized delivery on therapeutic outcomes and adverse events.

Main Methods:

• Co-delivery of programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) and cytotoxic T Lymphocyte antigen 4 (CTLA-4) inhibitors.
• Utilized an intratumoral drug delivery strategy.
• Administered reduced dosages of the combined inhibitors to patients with R/R advanced solid tumors.

Main Results:

• Four patients achieved a complete response lasting over 2 years, indicating favorable outcomes.
• The majority of treatment-related adverse events (TRAEs) were of low grade (1-2), suggesting a manageable safety profile.
• The intratumoral co-delivery approach demonstrated promising efficacy in R/R advanced solid tumors.

Conclusions:

• Intratumoral co-delivery of PD-1/PD-L1 and CTLA-4 inhibitors at reduced doses is a safe and effective strategy for R/R advanced solid tumors.
• This approach not only minimizes drug-related adverse events but also enhances anti-tumor immunity.
• The findings support the potential of localized combination immunotherapy to improve cancer treatment outcomes.