A novel nanotherapeutic approach has shown promising results in the treatment of one of the most lethal malignancies. JNJ-1900 (NBTXR3), developed by Nanobiotix, demonstrated favorable safety, feasibility, and encouraging early efficacy outcomes in patients with locally advanced or borderline resectable pancreatic ductal adenocarcinoma (PDAC), according to data presented at the 2025 Annual Meeting of the European Society of Radiation Oncology.
The Phase 1 trial (NCT04484909) conducted at The University of Texas MD Anderson Cancer Center evaluated 22 patients, with 20 diagnosed with locally advanced disease and 2 with borderline resectable pancreatic cancer. Results revealed a median overall survival (OS) of 23 months from diagnosis (95% CI, 17-not reached), which compares favorably to the 19.2 months observed in a historical review of 144 patients with locally advanced pancreatic cancer who received standard-of-care treatment at the same center.
"Patients with locally advanced or borderline resectable pancreatic cancer face a particularly urgent unmet need for therapeutic innovation that can provide a meaningful survival benefit with an acceptable safety profile," said Eugene J. Koay, MD, PhD, Associate Professor of Gastrointestinal Radiation Oncology at MD Anderson and principal investigator of the study.
Treatment Approach and Study Design
JNJ-1900 is an oncologic agent composed of functionalized hafnium oxide nanoparticles that are injected intratumorally and activated by radiotherapy. Its mechanism of action is designed to induce tumor cell death when activated by radiotherapy, triggering adaptive immune response and long-term anti-cancer memory.
In the Phase 1 study, patients received intratumoral NBTXR3 on day 1 of treatment following induction chemotherapy. Between days 15 and 43 of treatment, patients underwent 15 fractions of radiation therapy (45 Gy) in the absence of progressive disease or unacceptable toxicity.
The primary endpoint was to determine the recommended Phase 2 dose of radiotherapy-activated NBTXR3. Secondary endpoints included safety, injection feasibility, anti-tumor responses, and time-to-event outcomes, while exploratory endpoints examined pharmacokinetics, resectability conversion rates, surgical outcomes, and biomarkers of response.
Key Efficacy Findings
Beyond the improved overall survival, the study reported a median local progression-free survival (PFS) of 13.3 months following completion of radiation. Notably, two patients with locally advanced pancreatic cancer achieved R0 surgical resection, indicating complete removal of the tumor with no cancer cells seen at the margin of the resected specimen.
"Given the extremely poor survival rates in locally advanced and borderline resectable pancreatic cancer, the results from this Phase 1 study give us confidence in the potential of JNJ-1900 to serve as a meaningful addition to the treatment landscape," said Louis Kayitalire, MD, Chief Medical Officer at Nanobiotix.
Biomarker Insights
The exploratory biomarker analyses provided particularly intriguing findings. Among 20 patients with available circulating tumor mutational burden (cTMB) data, 40% exhibited increased cTMB, which was associated with improved local PFS and OS.
Furthermore, normalization of CA19-9, a tumor marker that serves as a surrogate for overall survival benefit, was observed in 59% of patients in the study. This compares favorably to an MD Anderson historical review of 243 patients with locally advanced pancreatic cancer, which showed CA19-9 normalization in only 17% of patients treated with standard-of-care therapy.
Next Steps in Development
Based on these encouraging results, the FDA has granted clearance for an expanded study that includes a new cohort combining JNJ-1900 with standard-of-care concurrent chemoradiation (capecitabine or 5-FU) following induction chemotherapy. The first patient in this new cohort has already been treated, and recruitment is ongoing.
The investigators concluded that these results support further evaluation of JNJ-1900 in a randomized study. This development represents a potential breakthrough in the treatment landscape for pancreatic cancer, which remains one of the most challenging malignancies to treat effectively.
Pancreatic ductal adenocarcinoma is characterized by aggressive tumor biology and limited responsiveness to standard therapies. For patients with locally advanced or borderline resectable disease, the current standard-of-care—induction chemotherapy followed by chemoradiation—rarely delivers curative outcomes, underscoring the urgent need for novel treatment approaches like JNJ-1900.
The collaboration between Nanobiotix and MD Anderson continues to explore this promising therapeutic approach, with both organizations expressing optimism about the potential impact on patient outcomes in this difficult-to-treat cancer.
