TLR9 and melanoma: In a Phase 1b trial, the TLR-9 agonist CMP-001 was able to overcome resistance to PD-1 inhibition when combined with pembrolizumab.32 Likewise, in a Phase 1b/2 trial, addition of the TLR-9 agonist SD-101 to pembrolizumab restored tumour sensitivity to PD-1 inhibition in refractory tumours; responses were seen in both injected and uninjected lesions.33 A Phase 2 trial of T-VEC plus pembrolizumab is ongoing in patients with advanced melanoma whose disease progressed following anti-PD-1 therapy.103