• Oncofocus Team

​PD-1/PD-L1 Combination Strategies

Focus - Melanoma Indication


Malignant melanoma is a complex, multifactorial disease, which is responsible for up to 75% of skin cancer-related deaths globally.


With the US FDA approval of ipilimumab (CTLA-4 targeting agent) in 2011 for the treatment of advanced melanoma patients, clinical research intensity has gradually shifted towards Immune Checkpoint Inhibitors (ICIs) & their Combination agents.


With the approval of nivolumab and pembrolizumab (both are PD-1 targeting agents), it is imperative to understand how the PD-1/PD-L1 clinical landscape is evolving in melanoma.


​​ We had three specific objectives



We zeroed in on ​382 clinical trials



And identified 33 PD-1/PD-L1 inhibitors


20 PD-1 Inhibitors 1 Bi-specific PD-1/PD-L1 inhibitor 12 PD-L1 Inhibitors



We observed the following three major combination strategies:


- increasing tumor immunogenicity

- reversing tumor immunosuppression

- targeting other signaling pathways that promote growth & proliferation



Top three PD-1 combinations: CTLA4, Vaccines, and Radiation therapy



Bringing everything together


To build upon the clinical gains observed with immunotherapeutic agents, several companies/organizations are actively researching combination of ICIs with different agents. With respect to PD-1/PD-L1, there are about 400 clinical trials investigating 33 inhibitors either as monotherapy or in combination.


The combination of PD-1/PD-L1 targeting agents with CTLA4 targeting agents is the most common combination strategy. Redundancy?


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