Responder-derived FMT and anti-PD-1 in PD-1 refractory melanoma and NSCLC

Solid Tumors
Diwakar Davar, MD, MSc
University of Pittsburgh


Cancer cells evolve and develop protective mechanisms to hide themselves from cancer killing T-cells. Immune checkpoint inhibitors (ICI), block these protective mechanisms by targeting PD-1/PD-L1 (or CTLA-4), unhiding cancer cells so that they can be killed by T-cells. While ICIs have become the standard of care for many cancer types including melanoma and non-small cell lung cancer (NSCLC), the majority of patients either do not respond or do not respond durably. Thus, there is a need to develop new treatment modalities to overcome treatment resistance and maximize therapeutic benefit. The intestinal microbiome is a group of organisms that have co-evolved with humans over time and they contribute to the development and function of the immune system. The researchers previously conducted a study that assessed responder-derived fecal microbiota transplantation (R-FMT) in patients with PD-1 resistant melanoma and found that a third of patients were resensitized following the R-FMT. This phase II study will assess R-FMT in patients with PD-1 relapse/refractory melanoma in combination with pembrolizumab and Lenvatinib and PD-1 relapse/refractory NSCLC in combination with pembrolizumab. Pembrolizumab is an immune checkpoint inhibitor targeting PD-1 and Lenvatinib was found to induce a response in 21% of patients with PD-1 relapse/refractory melanoma in one study. This study hopes to re-sensitize patients to pembrolizumab and enhance the response to Lenvatinib.

Trial Registration: Identifier: NCT05669846