Safety and efficacy of intratumoral (IT) ruxotemitide (LTX 315) in combination with pembrolizumab in patients with unresectable advanced melanoma or triple-negative breast cancer (TNBC).

Abstract

2602 Background: Advanced unresectable cutaneous melanoma or TNBC are associated with poor prognosis and limited treatment options. Ruxotemitide is an oncolytic peptide that induces immunogenic cell death and reshapes the tumor microenvironment to boost antitumor immune responses. We report aggregate safety and efficacy from two trials that assessed intratumoral ruxotemitide combined with pembrolizumab in patients with advanced or metastatic melanoma or TNBC. Methods: Two studies enrolled respectively patients with melanoma stage IIIB–IV (M1b) or unresectable TNBC and at least one injectable lesion (as cutaneous, subcutaneous or lymph node). Patients with melanoma were required to have failed prior PD-1\PD-L1 blockers treatment while TNBC patients were naïve of immunotherapy. Patients were required to have adequate organ function. Patients received IT ruxotemitide (up to seven injections during the first 29 days) in combination with pembrolizumab 200 mg IV every 3 weeks until disease progression or for up to 24 months. Safety and efficacy were analyzed across both studies. Tumor assessments were based on RECIST v1.1. Results: 41 patients were enrolled, with a median age of 61 years. 26 of pts (63.4%) had received three or more prior lines of therapy, and 22 pts (53.7%) had previous checkpoint blockade treatment. 22 patients (53.7%) had melanoma, 18 patients TNBC (43.9%) and 1 patient (2.4%) a carcinoid tumor. 4 patients had a partial response (2 with melanoma and 2 with TNBC). All responses in melanoma patients were durable, lasting more than 24 months. 1 patient with TNBC achieved a PR for one year. The safety profile was consistent with known effects of IT immunotherapy and pembrolizumab. The most common treatment emergent adverse events (TEAEs) related to ruxotemitide were injection-site reactions (78%), injection site erythema (26.8%), fatigue (22%), hypotension, injection site swelling or pruritus (14.6% each). Grade 3 TEAEs related to ruxotemitide included injection site pain (19.5%) and hypertension (4.9%). There were no related grade 4 TEAEs or deaths. Conclusions: IT ruxotemitide plus pembrolizumab demonstrated durable antitumor activity and manageable safety in heavily pretreated patients with advanced or metastatic melanoma or TNBC with injectable disease. These findings support further clinical evaluation of this combination in melanoma and TNBC. Clinical trial information: NCT01986426 and NCT04796194 .