Nanobiotix announced promising Phase 1 results for its radiotherapy-activated drug JNJ-1900 (NBTXR3) in combination with immune checkpoint inhibitors for patients with primary cutaneous melanoma who had developed resistance to anti-PD-1 therapy. The data, presented at the 2025 ImmunoRad conference in Paris, showed early efficacy signals in a heavily pre-treated population whose cancer had progressed despite multiple prior therapies.
Study Population and Design
The Phase 1 Study 1100 enrolled patients with advanced primary cutaneous melanoma who had exhausted standard treatment options, including anti-PD-1 therapy, ipilimumab, T-VEC, TIL, and radiotherapy. All 21 patients received a one-time intratumoral injection of JNJ-1900 (NBTXR3) followed by radiotherapy and sequential anti-PD-1 therapy with either pembrolizumab or nivolumab. Of these patients, 19 were evaluable for tumor response as of the August 21, 2025 data cutoff.
"The patients in this analysis represent one of the more difficult clinical challenges we face as many have exhausted standard therapies, including checkpoint inhibitors," said Study 1100 Coordinating Investigator Colette Shen, MD, PhD, Assistant Professor of Radiation Oncology at the University of North Carolina Lineberger Comprehensive Cancer Center.
Safety Profile and Dosing
The study established a recommended Phase 2 dose of 33% of gross tumor volume, with injection feasibility confirmed at this level. The treatment demonstrated a favorable safety profile across all 21 patients. In total, 16 patients experienced grade 1, grade 2, or grade 3+ treatment-emergent adverse events related to the overall therapeutic regimen, which included radiotherapy, anti-PD-1 therapy, JNJ-1900, and the injection procedure.
Of particular note, only 5 patients experienced adverse events specifically related to JNJ-1900 and the injection procedure, with just 1 patient experiencing grade 3+ events consisting of hypotension and pleuritic pain.
Efficacy Results
JNJ-1900 demonstrated preliminary efficacy signals in the 19 evaluable patients. The best observed objective response rate in all lesions reached 47.4% (9/19) per RECIST 1.1 criteria, including 4 complete responses and 5 partial responses. The best observed disease control rate achieved 78.9% (15/19) in all lesions.
Notably, in tumors that received JNJ-1900 injection and irradiation, investigators observed a 100% disease control rate (19/19). The median overall survival reached 14.6 months with a 95% confidence interval of 10.7 to 16.7 months across all 21 treated patients.
Mechanism and Systemic Effects
A significant finding emerged regarding the relationship between local and systemic responses. Investigators observed a correlation between the depth of local response in treated tumors and systemic tumor regression, suggesting possible immune system priming or re-activation.
"Notably, the relationship we observed between the depth of local response and systemic tumor regression further supports our hypothesis regarding the potentially broad applicability of JNJ-1900 (NBTXR3) for patients with cancer," said Louis Kayitalire, MD, Chief Medical Officer of Nanobiotix.
Drug Development Background
JNJ-1900 (NBTXR3) represents a novel oncology product composed of functionalized hafnium oxide nanoparticles administered via one-time intratumoral injection and activated by radiotherapy. The drug candidate achieved proof-of-concept in soft tissue sarcomas through a successful randomized Phase 2/3 study in 2018.
The mechanism of action is designed to induce significant tumor cell death in the injected tumor when activated by radiotherapy, subsequently triggering adaptive immune response and long-term anti-cancer memory. Given its physical mechanism, Nanobiotix believes JNJ-1900 could be scalable across any solid tumor treatable with radiotherapy.
Regulatory Status and Future Development
The U.S. Food and Drug Administration granted Fast Track designation for JNJ-1900 activated by radiation therapy in February 2020 for patients with locally advanced head and neck squamous cell carcinoma who are not eligible for platinum-based chemotherapy.
The drug development program is led by NANORAY-312, a global randomized Phase 3 study in locally advanced head and neck squamous cell cancers. Additionally, a Phase 2 randomized controlled clinical trial in patients with stage 3 unresectable non-small cell lung cancer, sponsored by Johnson & Johnson and dubbed CONVERGE, was initiated in the first quarter of 2025.
Investigators concluded that the melanoma data warrant further investigation in randomized clinical trials as a potential new treatment option for patients with primary cutaneous melanoma who are naïve or refractory to anti-PD-1 therapy.
