Hensify (crystalline hafnium oxide)

P3, N=500, Recruiting, Nanobiotix | Trial completion date: Jan 2026 --> Jun 2027 | Trial primary completion date: Jul 2024 --> Jun 2026

P1, N=24, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting

Mice achieving remission through NBTXR3 + PRT + αPD1 exhibited a robust memory immune response, effectively inhibiting growth of subsequent tumors from three distinct lung cancer cell lines. Proton IRT combined with NBTXR3 offers enhanced tumor control and survival rates over photon-based treatments in managing αPD1-resistant lung cancer, indicating its potential as a potent systemic therapy.

P1, N=24, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Mar 2024 --> Mar 2026 | Trial primary completion date: Mar 2024 --> Mar 2026

P1, N=24, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

P1, N=145, Recruiting, Nanobiotix | Trial primary completion date: Mar 2023 --> Apr 2027

P1, N=24, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Oct 2023 --> Oct 2025 | Trial primary completion date: Oct 2023 --> Oct 2025

The raw volume of NBTXR3 injected in the pancreas did not significantly change over the duration of the three weeks of treatment. We also did not observe significant changes in the NBTXR3 volume overlapping the GTV in most cases. The stability of NBTXR3 was demonstrated during RT.

NBTXR3 IT injection followed by activation with RT was confirmed to be feasible and well tolerated in elderly or frail patients with LA HNSSC and significant comorbidities. The high rate of best overall response suggests that NBTXR3+RT is effective in this elderly population ineligible to cisplatin with a high unmet medical need. These results support our ongoing phase III study comparing NBTXR3/RT ± cetuximab vs. RT ± cetuximab in platinum-based chemotherapy ineligible elderly patients with LA-HNSCC: NANORAY 312 (NCIT04892173).

Conclusions The RP2D of NBTXR3 for LAPC is 42% of GTV. The successful CR and shift to resectability in this patient population, along with the response and CA19-9 decrease and normalization suggest promising anti-tumor efficacy of NBTXR3/RT.

This response was further significantly enhanced by the injection of the tumor to be irradiated with NBTXR3 nanoparticles. Tumors of mice treated with the triple combination exhibited increased infiltration and activation of cytotoxic immune cells. This triple combination eradicated both tumors in 37.5% of the treated mice and showed robust long-term immunity to cancer.

Patients will receive a single intratumoral injection of the nanoparticles, followed by radiotherapy and intravenous infusion of fluorouracil or oral capecitabine concurrently. This study will be the first prospective, open-label, single-arm, nonrandomized study to investigate the efficacy and safety profile of PEP503 (NBTXR3) nanoparticles with radiotherapy and chemotherapy in these patients. Trial registration number: NCT02465593 (ClinicalTrials.gov).

P1/2, N=40, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

Following LMP, we measured a significant increase of in lipid peroxidation. These first elements allow a better understanding of the early biological consequences induced by NBTXR3+RT, compared to RT alone.

Our results strongly attest to the efficacy and validity of combining nanoparticle-enhanced radiotherapy and simultaneous blockade of multiple immune checkpoint receptors and provide a pre-clinical rationale for investigating its translation into human patients.

P1, N=145, Recruiting, Nanobiotix | N=60 --> 145 | Trial completion date: Mar 2023 --> May 2028

These results indicate that radiotherapy-activated NBTXR3 can act as an effective immunomodulator, modifying tumor cell immunogenicity and impacting the lymphocyte population.

Simultaneous inhibition of LAG3 and TIGIT in tandem with PD1 blockade and NBTXR3-enhanced radiotherapy promotes immune activation at the irradiated site. In addition, abscopal immune responses are improved with blockade of LAG3 and TIGIT. These results suggest that blockade of multiple immune checkpoints in parallel with NBTXR3-mediated radiotherapy may be effective in metastatic cancers.[Y.H.

NBTXR3 nanoparticle in combination with radioimmunotherapy significantly improves anti-PD1 resistant lung tumor control via promoting antitumor immune response.

The clinical efficacy of NBTXR3+RT has been demonstrated as a single agent in STS. Here we demonstrate that it overcomes resistance to anti-PD-1 treatment mechanisms in mice and led to tumor regression in patients having progressed on anti-PD-1 therapy. These results highlight the potential of NBTXR3+RT to positively impact the immuno-oncology field.

This Science Highlights session will showcase abstracts that are noteworthy in the field of Radiation and Cancer Biology.  The abstracts that will be discussed during this session are: A targeted gene expression risk score predicts meningioma outcomes and responses to radiotherapy Identification of De Novo Pyrimidine Synthesis as a Targetable Vulnerability in a Novel IDH1 Mutant Engineered Astrocytoma Model Overcoming resistance to anti-PD-1 with tumor agnostic NBTXR3: from bench to bedside Focal Adhesion Kinase drives resistance to therapy in HPV-negative head and neck squamous cell carcinoma in a p53-dependent manner CDK4/6 Inhibition and Radiation as a Treatment Strategy to Improve Local Disease Control in Breast Cancers with Poor Prognoses SIRT2 promotes murine melanoma progression through natural killer cell inhibition Click here to view this session on the Digital XP. Be sure to log in.

The clinical efficacy of NBTXR3+RT has been demonstrated as a single agent in STS. Here we demonstrate that it overcomes resistance to anti-PD-1 treatment mechanisms in mice and led to tumor regression in patients having progressed on anti-PD-1 therapy. These results highlight the potential of NBTXR3+RT to positively impact the immuno-oncology field.

Furthermore, Nanostring transcriptomic analysis of cells isolated from the tumors of mice thus treated showed evidence of classical two-step immunological priming, with an elevation of innate immune genes at the primary tumor and full-blown activation of the immune system within the secondary tumor. Conclusions Blockade of TIGIT and LAG3 with NBTXR3+XRT+aPD1 improved CD8+ T-cell proliferation, augmented the antitumor response at both irradiated and unirradiated (abscopal) tumors, and induced potent long-term antitumor memory in mice.

P2, N=60, Recruiting, M.D. Anderson Cancer Center

These data show that radiotherapy-activated NBTXR3 could increase local and distant tumor control through immune system priming. Our results may have important implications for immunotherapeutic agent combination with radiotherapy.

To date, three patients have been treated, one in cohort 1, two in cohort 2. Research Funding: Nanobiotix, SA

P1, N=60, Recruiting, Nanobiotix | Not yet recruiting --> Recruiting | Phase classification: P1/2 --> P1 | N=125 --> 60

Clinical trial information: NCT03589339. Research Funding: Nanobiotix, S.A.

Clinical trial information: NCT03589339. Research Funding: Nanobiotix, S.A.

Funding: Nanobiotix, SA. Clinical trial identification: NCT03589339.