Abstract PR05: Changing the radiation and immune-oncology paradigm in patients with head and neck squamous cell carcinoma (HNSCC) with the radioenhancer NBTXR3: From bench to bedside
Bibliographic record
Abstract
Abstract Purpose/Objectives: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, yet most patients (pts) ultimately develop ICI resistance. Overcoming this resistance is a major clinical challenge. Radiation therapy (RT) has emerged as a promising combination with ICIs since in some settings it may produce an immunomodulatory effect. NBTXR3, a novel radioenhancer composed of functionalized hafnium oxide nanoparticles, is administered by a single intratumoral injection. NBTXR3 increases RT energy deposition inside tumor cells, subsequent tumor cell death, and tumor antigen release and thus in combination with ICI may overcome resistance. Materials/Methods: Pre-Clinical: Abscopal assays were conducted in immunocompetent mice. Anti-PD-1 sensitive or resistant lung tumor cell lines were injected in both legs. Intratumoral NBTXR3 injection (or vehicle) followed by RT was performed in right leg (primary) tumors only. Some mice also received anti-PD-1 injections alone or in combination with anti-LAG3 and anti-TIGIT. Tumor growth was monitored, and immune cell infiltrates analyzed by IHC. Clinical: A multicenter phase I trial [NCT01946867] is evaluating NBTXR3/RT in pts with AJCC 8th stage III-IVA or T3, T4 SCC of the oral cavity or oropharynx ineligible to cisplatin. Pts received NBTXR3 at the recommended dose (22% of baseline tumor volume) followed by RT (IMRT 70 Gy in 35 fractions). A multicenter phase I trial [NCT03589339] is evaluating NBTXR3/RT/anti-PD-1 in 3 cohorts of pts with advanced solid tumors eligible for anti-PD-1: 1) Locoregional recurrent or recurrent and metastatic HNSCC, 2) Lung metastases, or 3) Liver metastases. NBTXR3 was administered by intratumoral injection. Stereotactic Body RT (SBRT) was delivered at tumor site-specific doses per standard practice. Results: Pre-clinical studies demonstrated that NBTXR3/RT induces an immune response not observed with RT alone and enhances systemic control. IHC showed significant increase of CD8+ T-cell infiltrates in both NBTXR3/RT-treated and untreated tumors. NBTXR3/RT/anti-PD-1 improved local and systemic control in mice bearing anti-PD-1 resistant tumors, produced long-term memory, and reduced spontaneous lung metastases. NBTXR3/RT/anti-PD-1/anti-LAG3/anti-TIGIT improved tumor control, extended survival and produced a robust long-term memory anti-tumor immune response. Clinically, NBTXR3 intratumoral injection was feasible and safe. Preliminary signs of efficacy observed in pts with locally advanced HNSCC treated with NBTXR3/RT will be presented. Preliminary signs of efficacy were observed in pts treated with NBTXR3/RT/anti-PD-1 including in pts resistant to anti-PD-1, as well as in remote non-irradiated lesions. Responses in pts with HNSCC will be presented. Conclusions: With demonstrated radioenhancement as well as immune system priming, NBTXR3 positions itself to be a paradigm shift catalyst in the treatment of pts with head and neck cancers. These data support further development of NBTXR3/RT alone as well as in combination with anti-PD-1 and/or other ICIs. Citation Format: Colette J. Shen, Christophe Le Tourneau, Zoltán Takacsi-Nagy, Xavier Liem, Jessica Frakes, Jiaxin Niu, Jared Weiss, Jimmy Caudell, Yun Hu, James W. Welsh, Sebastien Paris, Anais Debard, Patricia Said, Pavel Tyan, Tanguy Y. Seiwert, Zsuzsanna Papai, Omar I. Vivar, Leonard A. Farber, Ari Rosenberg. Changing the radiation and immune-oncology paradigm in patients with head and neck squamous cell carcinoma (HNSCC) with the radioenhancer NBTXR3: From bench to bedside [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PR05.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".