Intratumoral Ruxotemitide Combo Yields Activity in Advanced Melanoma

The landscape of immunotherapy for advanced melanoma continues to evolve as researchers investigate novel ways to overcome resistance to PD-1/PD-L1 inhibitors. At the 2026 American Association for Cancer Research (AACR) Annual Meeting, clinical data were presented on ruxotemitide (LTX-315), a first-in-class non-viral oncolytic peptide. By inducing necrosis-driven immunogenic cell death directly within the tumor microenvironment, ruxotemitide may turn "cold" tumors "hot." The phase 2 ATLAS-IT-05 study (NCT04796194) specifically examined whether combining this intratumoral approach with pembrolizumab (Keytruda) could provide a meaningful clinical benefit for patients who had already progressed on prior checkpoint inhibitors.

Top 3 Key Takeaways

1. Encouraging Clinical Benefit in Refractory Populations: The study reported an objective response rate (ORR) of 13.6% (80% CI, 5.117%-27.894%; 90% CI, 3.822%-31.591%) and a clinical benefit rate (CBR) of 40.9% (80% CI, 26.416%-56.752%; 90% CI, 23.272%-60.484%) among 22 evaluable patients. While no complete responses were observed, the achievement of partial responses in 13.6% of patients and stable disease in 27.3% in a population where prior PD-1 therapy had failed them suggested that the combination may re-sensitize some tumors to immune checkpoint blockade.
2. Evidence of Abscopal and Systemic Immune Activity: One of the most significant findings was the regression of both injected and non-injected (distal) lesions. Imaging and clinical photography demonstrated a reduction in tumor burden away from the site of the ruxotemitide injection, supporting the hypothesis that local treatment can trigger a systemic, tumor-specific T-cell expansion and a broader immune response.
3. Manageable Safety Profile with No New Signals: The combination was generally well-tolerated, with most treatment-emergent adverse events (TEAEs) being grade 1/2. Common adverse effects included injection site reactions (erythema [43.5%] and swelling [26.1%]) and additional TEAEs like fatigue (34.8%) and constipation (30.4%). Importantly, no grade 5 TEAEs were reported, indicating that adding ruxotemitide to the standard pembrolizumab regimen does not significantly increase the toxicity burden for patients.

ATLAS-IT-05 Study Background

Overall, 23 patients were enrolled and had to have histologically confirmed stage IIIB to IVm1b unresectable melanoma with confirmed disease progression on or after PD-1/PD-L1 inhibitor therapy. Additionally, patients must have had 3 or fewer lines of systemic therapy for metastatic disease, at least 1 being superficial. For injection, patients needed a non-visceral tumor, no ocular or mucosal melanoma diagnosis, adequate organ function, and a lactate dehydrogenase of 2 or less by ULN.

End points included ORR, CBR, progression-free survival, overall survival, and safety.

In phase A of the study, patients were given ruxotemitide on 7 dosing days for weeks 1 to 5 plus pembrolizumab at 200 mg on days 1 and 22. In phase B, there were no ruxotemitide dosing days, including pembrolizumab at 400 mg on day 43 and every 6 weeks until discontinuation or a maximum of 24 months of therapy.

The median patient age was 68 years, with 56.5% being older than 65. Overall, 56.5% of patients were male, 39.1% had received 4 or more lines of therapy, and 95.7% had melanoma. The mean time from initial diagnosis to study treatment was 65.01 months. At screening, 34.8% of patients had stage IV m1a disease, 60.9% had metastatic disease sites noted as “other”, and 69.6% did not have a BRAF mutation.

Reference

Dalle S, Diab A, Kirkwood M, et al. Intratumoral (IT) ruxotemitide (LTX‑315) in combination with pembrolizumab in patients with unresectable advanced melanoma refractory to PD-1/PD-L1 therapy: Final results from the ATLAS-IT-05 study. Presented at the 2026 American Society for Cancer Research, San Diego, CA; April 17-22, 2026. Poster 3810/25.