BO-112 Plus Pembrolizumab for Patients With Anti-PD-1-Resistant Advanced Melanoma: Phase II Clinical Trial...

Area of Science:

• Oncology
• Immunotherapy
• Clinical Trials

Background:

• Melanoma patients resistant to anti-PD-1 therapy lack established treatment options.
• BO-112, an intratumoral Toll-like receptor 3 agonist, has demonstrated potential in overcoming resistance in solid tumors.
• This study investigates the efficacy and safety of combining BO-112 with pembrolizumab in this patient population.

Purpose of the Study:

• To evaluate the objective response rate (ORR) of intratumoral BO-112 plus intravenous pembrolizumab in patients with anti-PD-1-resistant melanoma.
• To assess secondary endpoints including progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety.
• To determine if this combination therapy can overcome resistance to anti-PD-1 treatment in melanoma.

Main Methods:

• A Phase II clinical trial (NCT04570332) involving 42 patients with anti-PD-1-resistant melanoma.
• Patients received weekly intratumoral BO-112 for 7 weeks, then every 3 weeks, combined with pembrolizumab every 3 weeks.
• Primary endpoint was RECIST 1.1 ORR in the modified intention-to-treat (mITT) population; secondary endpoints included PFS, OS, DOR, and safety.

Main Results:

• The study met its primary endpoint with a 25% ORR in the mITT population (40 patients).
• Objective responses included 10% complete responses and 15% partial responses, with 40% achieving stable disease.
• Median PFS was 3.7 months, and 54% of patients were alive at 24 months. The combination was well-tolerated with manageable adverse events.

Conclusions:

• The combination of BO-112 and pembrolizumab demonstrated a significant objective response rate, meeting the primary endpoint.
• This therapeutic strategy shows potential for overcoming anti-PD-1 resistance in melanoma patients.
• Progression-free survival aligns with other studies in this resistant setting, and overall survival data are promising.