Intralesional anti-PD1 treatment in patients with metastatic melanoma: The pilot study.

Abstract

188 Background: Systemic anti-PD1 treatment is major advantage for metastatic melanoma patients over the last five years. Nevertheless up to the moment there are no solid predictive factors discovered. On the other hand immune related adverse events develop quite frequent and sometimes could be dangerous. Methods: Patient with advanced cutaneous melanoma with known BRAF status and at least one superficial lesion (suitable for injection) are eligible. One of two commercially available anti-PD1 drugs (nivolumab or pembrolizumab) is administered intralesionaly to patients every 2 weeks with total daily dose not more than 50 mg (5 ml) using a scale-base approach depending on lesions size. Clinical and immunological outcomes assessed every 12 weeks. For assessing lymphoid infiltrate tumor biopsy performed before treatment and on week 12. To detect a systemic objective response rate of 50% with sensitivity of 80% and error type alfa 5% at least 25 patients to be included. Interim analysis was preplanned when 3 (25%) of events occurred. Results: Among 7 pts OR was detected in 4 (54.7%), PD in 3 (42.9%). Bystander effect was seen in 2 of 4 patients (50%). Among 3 non-responders 2 failed to salvage systemic anti-PD1 treatment and one is now on anti-CTLA4. The most common adverse event was injection site pain, which was self-limiting. Baseline immune phenotype of tumor infiltrating lymphocytes (TILs) was available for 5 of 7 pts included. Baseline percent of TILs, CD3+CD8+ and CD8+CD279+ was higher in responders vs non-responders (3.6±4.08% vs 0.8±0, NS, 75.1±20.6% vs 54.8±1.13, NS; 36.75±18.7% vs 42.8±13.1, NS respectively ). Baseline difference in CD11b+CD28- between responders (7.06±7.768) and non-responders (25.0 ±0.00) was statistically significant. Conclusions: these results demonstrates feasibility, tolerability and potential clinical efficacy of intralesional anti-PD1 in melanoma patients. Further study are needed to determine if unsuccessful intralesional administration could predict failure to systemic treatment as well as TILs phenotype could predict intralesional or systemic anti-PD1 clincal benefit Clinical trial information: MEL004IL.

Current Role and Status for Intratumoral Injection Therapies in Metastatic Melanoma

“…Seven patients were treated with IT injections of either pembrolizumab or nivolumab in a phase I trial with dosing per a predetermined scale based on lesion size up to a maximum of 50 mg injected every 2 weeks. 31 Responses were seen in 4 patients. Of the 3 patients who had disease progression, 2 subsequently failed salvage systemic anti-PD-1 therapy.…”

“…Finally, some studies have investigated the role of IT checkpoint inhibitors in patients with melanoma. Seven patients were treated with IT injections of either pembrolizumab or nivolumab in a phase I trial with dosing per a predetermined scale based on lesion size up to a maximum of 50 mg injected every 2 weeks 31 . Responses were seen in 4 patients.…”

Intratumoral therapies and in-situ vaccination for melanoma

“…Interim analysis from a pilot study by Samoylenko et al recently demonstrated intralesional pembrolizumab or nivolumab resulted in an overall response in four out of the seven patients. 58 Additional studies are ongoing to study the safety and efficacy of intralesional CPI therapy in melanoma and other cutaneous malignancies, such as the use of intertumoral ipilimumab in combination with systemic nivolumab in patients with metastatic melanoma (NCT02857569) and the use of intratumoral nivolumab in patients with Kaposi’s sarcoma (NCT03316274).…”