NBXTR3 Plus Radio/ICI Shows Promising Results in Melanoma Trial

Data from the phase 1 Study 1100 (NCT03589339)¹ show a favorable safety profile and encouraging early signs of efficacy with the therapeutic candidate NBTXR3 (JNJ-1900) plus radiotherapy and an immune checkpoint inhibitor (ICI) in heavily pretreated patients with melanoma.²

Data from this cohort were presented at the 2025 ImmunoRad Conference. The study regimen consisted of a 1-time intratumoral injection of NBTXR3 followed by standard radiotherapy and sequential anti­–PD-1 therapy of pembrolizumab (Keytruda) or nivolumab (Opdivo).

Key takeaways from the study include an objective response rate of 47.4% and a disease control rate of 78.9% in evaluable patients. The median overall survival for all treated patients was 14.6 months.

Notably, investigators observed a direct relationship between the depth of local response in the injected tumor and systemic tumor regression, supporting the hypothesis that NBTXR3 may prime or reactivate an anticancer immune response. The findings are considered to warrant further investigation in randomized clinical trials as a potential new treatment option for this difficult-to-treat patient population.

In an interview with Targeted Oncology, Jason Chan, MD, radiation oncologist at the University of California San Francisco and investigator on Study 1100, discussed the findings and next steps of this research.

Targeted Oncology: What are the unmet needs in melanoma that prompted this research?

Jason Chan, MD: The unmet need in melanoma is that about half of patients with melanoma develop primary resistance to anti–PD-1therapy, and about one-fourth of patients will develop secondary resistance. So primary resistance, in in simple terms, is media therapy didn't work at all, or only worked for a short period of time. This is a big patient population.

Study 1100 had 3 different cohorts. Cohort 3 [investigated] NBTXR3 and radiation followed by immunotherapy in patients who have already had resistance to immunotherapy. Just by chance, a large number of the patients enrolled on this cohort were patients with melanoma.

Could you summarize your findings?

This was a phase 1 study, so the first thing that we found was that this combination of treatment was safe, specifically related to any [adverse] effects related to injection of NBTXR3. Any-grade toxicity was about 24%, so close to one-fourth of the patients. In terms of grade 3 toxicity or higher, there were 2 grade 3 toxicities that were that were related to the actual injection itself.

There were 19 patients with melanoma who had enough follow-up to assess response. The overall response was 47% in all patients. The disease control rate was 79% in these 19 patients.

Patients on the study had had oligometastatic disease, so they had up to 5 sites that were that that were either new or progressing, and the intervention was only to 1 site. The actual responses to the lesion that was intervened on were better, as might be expected. For the lesion that was actually injected and radiated, the response was 53%, and there was 100% disease control rate on the lesions that were actually intervened on.

What do you see as the next steps in this line of research?

We see an efficacy signal, but it's a phase 1 study, so this would need to be confirmed and in a larger study that was dedicated to a population of patients with melanoma, and in particular, patients that were very heavily pretreated. In addition to having resistance to anti–PD-1 therapy, have the patients had resistance to other to anti–CTLA-4 [agents]? Most patients had had failed prior treatments with other immunotherapy combinations. So, a larger study with specifically patients with melanoma and a more homogenous population to confirm the efficacy signal that we see.

REFERENCES:

1. NBTXR3 Activated by Radiotherapy for Patients with Advanced Cancers Treated with an Anti-PD-1 Therapy. ClinicalTrials.gov. Updated January 14, 2025. Accessed October 7, 2025. https://clinicaltrials.gov/study/NCT03589339

2. NANOBIOTIX Announces New Results From a Phase 1 Study Evaluating JNJ-1900 (NBTXR3) in Combination With Immune Checkpoint Inhibitors as a 2L+ Therapy for Patients With Primary Cutaneous Melanoma Resistant to Anti-PD-1. News release. Nanobiotix. September 17, 2025. Accessed October 7, 2025. https://tinyurl.com/4f9btu9w