NBTXR3 (JNJ-1900) Could Offer a New Therapeutic Option for Some Lung Cancer Patients

Data from the completed dose escalation part of a Phase 1 study evaluating radiotherapy-activated NBTXR3 (JNJ-1900)*/** as a second or later line (2L+) therapy for patients with locally advanced non-small cell lung cancer or NSCLC amenable to re-irradiation, shows promising results, including:

• Favorable safety profile without dose-limiting toxicities (DLTs) or Grade 3 or higher SAEs related to NBTXR3.
• Confirmed injection feasibility in 12 patients with locally advanced NSCLC amenable to re-irradiation for whom prior lines of therapy have failed.
• Recommended phase 2 dose (RP2D) was established at 33% of gross tumor volume.

In the study, researchers also observed a promising early efficacy signals. Preliminary review of survival data from 12 patients showed 12-month LPFS of 64% (median 18.6 months) and 12-month OS of 83% (median 30.2 months), further supporting the potential clinical benefit of NBTXR3 (JNJ-1900) in this patient population. [1]

These findings of the study, sponsored by The University of Texas MD Anderson Cancer Center, suggest NBTXR3 (JNJ-1900) could offer a new therapeutic option for lung cancer patients with no alternatives after prior treatments have failed.

The results were presented at the 2025 European Lung Cancer Conference, held in Paris, France, March 26 –  29, 2025, by study principal investigator Saumil Gandhi, MD, PhD, Department of Thoracic Radiation Oncology, Division of Radiation Oncology at MD Anderson.

Inoperable locally recurrent NSCLC
Reirradiation or ReRT of inoperable locally recurrent NSCLC after prior radiotherapy is often limited to palliative doses due to associated toxicities. NBTXR3 is a novel radioenhancer made of functionalized hafnium oxide nanoparticles administered by direct intra-tumoral injection and activated by RT to enhance tumor kill.

Locoregional recurrence occurs in 30-40% of patients with locally advanced NSCLC after treatment with definitive chemoradiation. Historically, patients who are amenable to re-irradiation are often limited to palliative doses due to associated toxicities. As such, strategies to enhance the therapeutic ratio of radiotherapy are needed to improve treatment outcomes.

“Patients with recurrence after prior radiation therapy for locally advanced lung cancer face limited therapeutic options and significant challenges in achieving durable disease control,” Gandhi said.

“The data underscore the need for continued therapeutic innovation for these patients and highlight the potential of NBTXR3 (JNJ-1900) as a novel approach to improving patient outcomes.”

New therapeutic option
“The Nanobiotix team is encouraged by these early findings, which suggest NBTXR3 (JNJ-1900) could offer a new therapeutic option for patients with no alternatives after prior treatments have failed,” noted Louis Kayitalire, MD, Nanobiotix Chief Medical Officer.

“Notably, the results were observed in patients who resisted prior curative radiation doses and that were treated with JNJ-1900 (NBTXR3) activated by a lower radiation dose. As we advance the study’s expansion phase, we look forward to further evaluating NBTXR3 (JNJ-1900)’s potential to improve patient outcomes.”

The expansion phase of the study is ongoing, with 5/12 patients injected to date.

A novel hafnium based product
NBTXR3 (JNJ-1900) is a novel, potentially first-in-class oncology product composed of functionalized hafnium oxide nanoparticles (HfO2 NPs) that is administered via one-time intratumoral injection and activated by radiotherapy. Hafnium is a chemically stable metallic with high atomic number and electron density [2]

The unique properties of hafnium oxide nanoparticles has shown to help in cancer imaging and diagnosis. Previous, unrelated studies, have demonstrating the excellent mass attenuation coefficient of hafnium oxide nanoparticles, and their ability to accumulate in tumor tissue and enhance irradiation, making them valuable X-ray and CT imaging contrast agents. [3][4][5][6][7] Additionally, Hf-based nanosensors have the capacity to aid in tumor diagnosis by detecting cytokines in various body fluids.

Proof-of-concept
A proof-of-concept was achieved in soft tissue sarcomas for which the product received a European CE mark in 2019.  The mechanism of action (MoA) 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 the physical MoA, Researchers at Nanobiotix believe that the investigational agent could be scalable across any solid tumor that can be treated with radiotherapy and across any therapeutic combination, particularly immune checkpoint inhibitors.

Multiple Solid Tumor Indication
Radiotherapy-activated NBTXR3 is being evaluated across multiple solid tumor indications as a single agent or in combination with anti-PD-1 immune checkpoint inhibitors, including in NANORAY-312—a global, randomized Phase 3 study in locally advanced head and neck squamous cell cancers.

In February 2020, the United States Food and Drug Administration (FDA) granted regulatory Fast Track designation for the investigation of NBTXR3 activated by radiation therapy, with or without cetuximab, for the treatment of patients with locally advanced HNSCC who are not eligible for platinum-based chemotherapy—the same population being evaluated in the Phase 3 study.

Pancreatic cancer
Results from a phase 1 study evaluating NBTXR3 (JNJ-1900) for patients with locally advanced pancreatic cancer (LAPC)or borderline resectable pancreatic cancer (BRPC) were also encouraging.

Patients with LAPC or BRPC often receive initial treatment with cytotoxic chemotherapy followed by RT +/- concurrent or maintenance chemotherapy.

This study was designed to evaluate the safety, feasibility, and early signs of efficacy of RT-activated NBTXR3 for patients with LAPC or BRPC after initial treatment with cytotoxic chemotherapy, in comparison to the historical data in patients who received RT +/- concurrent or maintenance chemotherapy after initial treatment with cytotoxic chemotherapy.

Investigators observed an mOS of 23 months from the date of diagnosis in 22 patients (20 with LAPC and 2 with BRPC) on the trial that compared favorably with outcomes at MD Anderson where the historical control for mOS in 144 patients treated at the same center was 19.2 months. Investigators concluded that RT-activated NBTXR3 was well tolerated by all patients and that the encouraging oncologic outcomes observed warrant further evaluation in a randomized trial.

Following these encouraging results from the study, MD Anderson submitted and received US FDA clearance for a new, additional study cohort evaluating the combination of NBTXR3 and standard-of-care concurrent chemoradiation. The new cohort has launched, and recruitment is ongoing.

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Note: * In 2019 Nanobiotix entered into a broad, comprehensive clinical research collaboration with The University of Texas MD Anderson Cancer Center to sponsor several Phase 1 and Phase 2 studies evaluating NBTXR3 across tumor types and therapeutic combinations.
** In 2023, Nanobiotix announced a license agreement for the global co-development and commercialization of NBTXR3 with Janssen Pharmaceutica NV, a Johnson & Johnson company.

Reference
[1] Gandhi SJ, Chang E, Chen A, MD, Chun SG, Lin SH, Maguire RC, Ning,  Bronk JK, Qian D, Chang JY, Welsh JW, Liao Z, Sheth RA, Casal RF. Phase 1 Study of Reirradiation (“ReRT”) with NBTXR3 (JNJ-1900) for Inoperable Locoregional Recurrent Non-Small Cell Lung Cancer (“NSCLC”) Poster/abstract #207P.
[2] Wang J, Pan J, Tang Y, Chen J, Fei X, Xue W, Liu X. Advances of hafnium based nanomaterials for cancer theranostics. Front Chem. 2023 Nov 24;11:1283924. doi: 10.3389/fchem.2023.1283924. PMID: 38075497; PMCID: PMC10704140.
[3] Martínez-Rovira I, Prezadoa Y. Monte Carlo dose enhancement studies in microbeam radiation therapy. Med Phys. 2011 Jul;38(7):4430-9. doi: 10.1118/1.3603189. PMID: 21859044.
[4] Mendoza JG, Frutis MA, Flores GA, Hipólito MG, Maciel Cerda A, Azorín Nieto J, Montalvo TR, Falcony C. Synthesis and characterization of hafnium oxide films for thermo and photoluminescence applications. Appl Radiat Isot. 2010 Apr-May;68(4-5):696-9. doi: 10.1016/j.apradiso.2009.09.031. Epub 2009 Sep 19. PMID: 19828322.
[5] Pottier A, Borghi E, Levy L. New use of metals as nanosized radioenhancers. Anticancer Res. 2014 Jan;34(1):443-53. PMID: 24403500.
[6] Frenzel T, Bauser M, Berger M, Hilger CS, Hegele-Hartung C, Jost G, Neis C, Hegetschweiler K, Riefke B, Suelzle D, Pietsch H. Characterization of a Novel Hafnium-Based X-ray Contrast Agent. Invest Radiol. 2016 Dec;51(12):776-785. doi: 10.1097/RLI.0000000000000291. PMID: 27299578.
[7] McGinnity TL, Dominguez O, Curtis TE, Nallathamby PD, Hoffman AJ, Roeder RK. Hafnia (HfO2) nanoparticles as an X-ray contrast agent and mid-infrared biosensor. Nanoscale. 2016 Jul 14;8(28):13627-37. doi: 10.1039/c6nr03217f. PMID: 27364973.

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