Andrea Boutros, Medical Doctor and Oncology Resident at San Martino Polyclinic Hospital, shared a paper Adi Diab and colleagues authored on X:
“New Phase III data on intratumoral immunotherapy in PD-1 refractory melanoma (ILLUMINATE-301)
Does intratumoral TLR9 activation enhance response to ipilimumab? A thread on the results and clinical implications.
Background
Advanced melanoma progressing after anti-PD-1 remains a therapeutic challenge.
Ines da Silva et al. (The Lancet Oncology 2021) showed that in PD-1 refractory melanoma, ipi-nivo has an ORR ~31%
ILLUMINATE-301 Design
Randomized Ipilimumab 3 mg/kg IV ± 9 intralesional Tilsotolimod (IMO-2125) – a synthetic TLR9 agonist.
481 patients (unresectable stage III-IV, PD-1 refractory)
Primary endpoints: ORR, OS.
Results
ORR (by independent review): 8.8% (Tilsotolimod + Ipi) vs 8.6% (Ipi alone)
No significant difference in response rates.
OS: 11.6 months vs 10 months (HR 0.96, p=0.7) No survival advantage.
Tilsotolimod (TLR9 agonist) + ipilimumab did not enhance ORR or OS vs ipi alone in refractory melanoma.
Why?
– TLR9 priming may be insufficient alone
– Only 23% completed all 9 injections
– 51% had high LDH
How do we improve post-PD-1 strategies in melanoma?”
Authors: Adi Diab et al.
