Replimune’s RP2 Shows Durable Responses in Advanced Solid Tumors

Replimune presented final Phase 1 data for RP2 at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, demonstrating durable anti-tumor activity and a favorable safety profile both as monotherapy and in combination with nivolumab in heavily pretreated patients with advanced solid tumors.

The first-in-human Phase 1 study (NCT04336241) enrolled 85 patients with cancers including uveal melanoma, colorectal cancer, head and neck cancer, pancreatic cancer, cutaneous melanoma, and sarcoma. Patients had received a median of two prior systemic therapies, while 42% had previously been treated with immune checkpoint inhibitors.

Multi-Mechanism Oncolytic Immunotherapy

RP2 is an engineered herpes simplex virus type 1 (HSV-1)-based oncolytic immunotherapy built on Replimune’s RP1 platform. It combines the fusogenic protein GALV-GP R⁻, GM-CSF, and an anti-CTLA-4 antibody-like molecule to enhance tumor cell killing, stimulate antigen presentation, and broaden anti-tumor immune responses.

The therapy is intended to convert immunologically “cold” tumors into inflamed tumors that are more likely to respond to immune-based treatment.

Clinical Activity and Durable Responses

Among 21 evaluable patients receiving RP2 monotherapy, the objective response rate (ORR) reached 19.0%, with responses observed in uveal melanoma, esophagogastric adenocarcinoma, chordoma, and mucoepidermoid carcinoma.

RP2 plus nivolumab achieved an ORR of 19.1% among 47 evaluable patients, while the disease control rate reached 48.9%.

Activity was particularly notable in uveal melanoma, where pooled responses across both treatment groups reached 33.3%, supporting further development in this difficult-to-treat disease.

Responses were durable. Median duration of response was not reached in the monotherapy cohort, while the combination cohort achieved a median duration of response of 22.1 months. Some responses remained ongoing beyond 35 months.

Tumor regression was observed in both injected and non-injected lesions, providing evidence of systemic immune activity beyond the injection site.

Biomarker and Safety Findings

Translational analyses showed that RP2 remodeled the tumor microenvironment and increased pathways associated with T-cell cytotoxicity and antigen presentation. Investigators also reported expansion of HSV-1-specific and tumor-associated MAGE T-cell receptor clones, supporting the therapy’s proposed mechanism of action.

RP2 was well tolerated both alone and with nivolumab. No Grade 4 or Grade 5 treatment-related adverse events or unexpected safety signals were reported. The most common adverse events were low-grade pyrexia, chills, and fatigue, consistent with immune activation.

Path Forward

RP2 is currently being evaluated with nivolumab in a randomized Phase 2/3 trial in metastatic uveal melanoma (NCT06581406). The durability of responses, favorable safety profile, and evidence of systemic immune engagement support continued development as the program advances into later-stage testing.

 Reference

Replimune Presents Final First-in-Human Data for RP2 in Advanced Solid Tumors During Oral Presentation at the 2026 American Society of Clinical Oncology Annual Meeting | Replimune Group Inc.