What is the future of immunotherapy? In this morning’s session, “The View Beyond Single-Agent Checkpoint Blockade” we got a glimpse into a potential path forward.
Single agent checkpoint blockade is becoming a mainstay of oncology treatment. But while the depth and durability of responses are impressive, even in highly immunogenic tumors, the majority of patients do not respond.
To improve response rates, various combinations are being investigated, but often the efficacy benefits are incremental and come with significant increases in toxicity.
This morning’s session focused on identifying and prioritizing combinations with non-redundant mechanisms of immune activation. Presentations highlighted 3 such examples: CTLA-4 inhibition with PD-1 pathway inhibition in SCLC, OX40 activation with PD-1 pathway inhibition in advanced solid tumors, and CAR-T therapy following lymphodepletion in ALL, CLL, and Non Hodgkins Lymphoma.
While all the data was exciting and impressive, a key point across all the presentations was that combination strategies may lead to efficacy in tumors previously believed to be unresponsive to immunotherapy.
The OX40 activation in combination with PD-1 pathway inhibition suggested it was able to alter pharmacodynamic changes within the tumor. And the PD-1 and CTLA-4 blockade showed improved responses in SCLC, a relatively “cold” tumor, (or one that is not particularly immunogenic).
Together these presentations highlight the need for further understanding of how to optimize combinations and identify patients that can benefit from therapy.