Phase 2, Open-Label, Multicenter Study of Nelitolimod in Combination with Pembrolizumab in Anti–PD-1 Treatment-Naïve Advanced Melanoma

Purpose: Nelitolimod (previously SD-101) is a toll-like receptor 9 agonist. We assessed whether intratumoral nelitolimod plus pembrolizumab potentiates antitumor activity in patients with advanced melanoma who had not previously received anti– PD-1/PD-L1 therapy. Patients and Methods: Patients with advanced melanoma who were naïve to anti–PD-1/PD-L1 therapy received either nelitolimod 2 mg injected into 1 to 4 lesions or nelitolimod 8 mg injected weekly into a single lesion for 4 weekly doses and then every 3 weeks. Pembrolizumab 200 mg was administered intravenously every 3 weeks. Results: Forty-five patients received nelitolimod 2 mg and 41 patients received nelitolimod 8 mg per injection. The objective response rate (ORR) was 76% in the 2-mg group and 49% in the 8-mg group. In those with distant metastases, ORRs in both treatment groups were similar to the overall ORRs. In the 2-mg group, treatment responses were similar in those with PD-L1–positive tumors and those with PD-L1–negative tumors. The progression-free survival rate at 18 months (landmark) was 62% in the 2-mg group and 40% in the 8-mg group. Forty-four patients (100%) in the 2-mg group and 37 patients (95%) in the 8-mg group experienced a treatmentrelated adverse event with either drug; overall, 31 patients (37%) had a grade 3 or 4 treatment-related adverse event related to either study drug. Conclusions: In patients with anti–PD-1/PD-L1 treatmentnaïve advanced melanoma, nelitolimod plus pembrolizumab induced objective responses, including in PD-L1–negative tumors. The treatment combination warrants further study in advanced melanoma.