The last six to eight weeks have been exceptionally invigorating here at AdventHealth Orlando — a period of deepening engagement with solid tumor cellular therapies, novel bispecifics, and intratumoral treatment approaches, along with expanding industry collaboration and new clinical trial opportunities. As we continue to refine care for patients with cutaneous and connective tissue malignancies, I am actively seeking partnerships with colleagues and industry leaders focused on melanoma, Merkel cell carcinoma, basal/squamous cell carcinomas, angiosarcoma, soft tissue and bone sarcomas. Please email me at sajeve.thomas.md@adventhealth.com and look forward to collaborating with you!
In that spirit, I want to highlight a set of intriguing data presented at the ESMO 2025 Annual Meeting (October, Berlin, Germany) on the combination of RP1 plus nivolumab in patients with non‑melanoma skin cancers and acral melanoma. The poster — presented by Dirk Schadendorf, MD — offers early insight into safety and efficacy across several rare tumor subsets where effective systemic options are often limited.
What Is RP1?
RP1 (referred to generically as vusolimogene oderparepvec) is a modified oncolytic herpes simplex virus engineered to:
- Express GM‑CSF, a cytokine known to enhance immune recruitment;
- Produce a fusogenic protein to increase tumor cell lysis;
- Stimulate local and systemic antitumor immune responses when delivered intratumorally.
Unlike conventional systemic immunotherapy, intratumoral agents like RP1 aim to both destroy tumor cells directly and prime the immune system against tumor antigens, potentially leading to responses at distant, uninjected sites. This “in situ vaccination” concept is one of the most compelling aspects of intratumoral therapy.
The ESMO 2025 Data: Study Overview
This analysis evaluated RP1 plus nivolumab in patients with advanced non‑melanoma skin cancers — including:
- Merkel cell carcinoma (MCC)
- Basal cell carcinoma (BCC)
- Angiosarcoma
- Cutaneous squamous cell carcinoma (cSCC)
Patients could be either PD‑1 therapy–naive or PD‑1 refractory, and cohorts ranged from ~14 to ~49 patients per tumor type:
- MCC: ~28 patients
- BCC: ~14 patients
- Angiosarcoma: ~14 patients
- cSCC: ~49 patients
Roughly one‑third across cohorts were PD‑1 naive, with the remainder being PD‑1 refractory — a particularly challenging population given historically lower response rates after checkpoint inhibitor progression.
Efficacy Signals Across Tumor Subsets
While the numbers are small and interpretation must be cautious, the response rates are notable:
- Merkel Cell Carcinoma: High overall response rate, with many patients responding; responses observed even in PD‑1 refractory disease.
- Basal Cell Carcinoma: Approximately 30–40% response rate in patients with prior PD‑1 exposure.
- Angiosarcoma: Similar range (~30–40%) in PD‑1 refractory settings.
- Cutaneous SCC: Lower response rates (~15–20%) in the refractory setting, but still evidence of activity.
Across PD‑1 naive patients, responses tended to be higher, particularly in angiosarcoma and MCC cohorts — suggesting that combinatorial immunotherapy may harness more robust antitumor immunity in earlier disease settings.
It’s important to emphasize that these are early, cohort‑level signals, not mature randomized data, but they do reinforce the potential of intratumoral therapy beyond melanoma.
In an separate ad hoc analysis presented at ESMO 2025, RP1 plus nivolumab demonstrated a 44% objective response rate in a small cohort of patients with acral melanoma — a rare and aggressive subtype representing just 2–3% of melanomas and historically resistant to immune checkpoint inhibition. With a median duration of response of nearly 12 months, this signal stands out in a population that typically fares poorly with standard therapies. Still, the small sample size (n=18), non-randomized design, and lack of detailed safety reporting temper how far we can extend these findings.
That said, the data underscore the need for more targeted trials in acral melanoma, and we’ll be watching closely for updates from the IGNYTE-3 phase 3 trial, which is evaluating RP1 plus nivolumab against physician’s choice in PD‑1/CTLA‑4–refractory melanoma.
Safety and Tolerability
The combination of RP1 plus nivolumab was generally well‑tolerated. Most adverse events were consistent with what we expect from intratumoral virus‑based therapies and immunotherapy combinations. No unexpected safety signals were highlighted in the ESMO poster.
Why Intratumoral Therapy Matters
Intratumoral immunotherapy occupies a unique niche:
- Direct oncolysis of injected tumors.
- Immune priming that can extend responses to non‑injected lesions.
- Potentially enhanced benefit when combined with systemic checkpoint inhibitors.
- Applicability across multiple tumor types, especially those with accessible lesions.
Approved intratumoral agents like T‑VEC have established this principle in melanoma and are included in NCCN guidelines for select indications, including cutaneous melanoma and Merkel cell carcinoma. (If patients have questions about currently approved options, they should always discuss these with their oncology care team.)
RP1 represents the next wave — with distinct immunologic engineering and promising early signals in rare skin cancers that have been historically difficult to treat after checkpoint resistance.
Looking Ahead
As we anticipate FDA review decisions later this year April 2026, including possible regulatory milestones for RP1 in malignant melanoma, it’s an exciting time for innovation in cutaneous oncology. Data presented at ESMO 2025 suggest that RP1 plus nivolumab shows promising activity in several advanced non‑melanoma skin cancers, including Merkel cell carcinoma, basal cell carcinoma, angiosarcoma, and cutaneous squamous cell carcinoma — both in patients who have and have not received prior PD‑1 therapy. Intratumoral immunotherapy offers a way to stimulate both local tumor cell destruction and systemic immune responses. Further study and clinical availability could expand options for patients with these disease types.
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. He brings a wealth of expertise to the complex and challenging world of oncology.
Disclosures:
Dr. Thomas serves as a speaker for BMS, Merck, Ipsen, Natera, Immunocore, Pfizer, Sun Pharma, SpringWorks. He also receives industry grants in support of numerous clinical trials.