Nanobiotix reports new data featuring NBTXR3 plus chemoradiation

Nanobiotix announced the reporting of new data at the 2022 Annual Meeting of the American Society for Clinical Oncology featuring potential first-in-class radioenhancer NBTXR3 in combination with concurrent chemoradiation for the treatment of head and neck cancer and rectal cancer. Nanobiotix also presented a trial-in-progress poster on the study design of the Company's ongoing pivotal phase 3 study, NANORAY-312, evaluating NBTXR3 as a single agent activated by radiotherapy for the treatment of elderly and frail patients with locally advanced head and neck squamous cell carcinoma who are ineligible for platinum-based chemotherapy. In view of the company's strategy for development of NBTXR3 as a product candidate that can integrate across solid tumor indications along with major treatment modalities within each indication, starting with head and neck cancer, the company believes these new data add support for the radioenhancer in combination with chemoradiation and as a neoadjuvant therapy with the potential to improve surgical outcomes. A Phase 1b/2 Study Evaluating NBTXR3 in Combination with Concurrent Chemoradiation for Patients with Locally Advanced or Recurrent Head and Neck Squamous Cell Carcinoma: This study, sponsored, executed, and reported by former Nanobiotix collaborator in Asia, PharmaEngine, sought to evaluate the safety and feasibility of NBTXR3 intratumoral injection when added to low-dose weekly cisplatin-containing CCRT for patients with locally advanced or recurrent head and neck squamous cell carcinoma. The study also aimed to establish the recommended phase 2 dose, however the RP2D was not determined due to stoppage of the phase 1b part of the trial resulting from the conclusion of the collaboration between PEI and Nanobiotix in 2021. Adult patients with T3-4 LA-HNSCC suitable for cisplatin were eligible for the study and 12 such patients were enrolled. These patients received a single intratumoral injection of NBTXR3, followed by a low-dose weekly regimen of CCRT. All 12 patients were deemed evaluable and all had stage 4 locally advanced disease. Of these evaluable patients, 3, 6, and 3 patients received NBTXR3 at the 5%, 10%, and 15% dose levels, respectively. No serious adverse events inconsistent with what would normally be expected from a low-dose CCRT regimen were observed. Dose-limiting toxicities of grade 3 increased ALT and grade 3 increased AST were observed in one patient at the 10% dose level. Common Grade 3 adverse events observed across dose levels were stomatitis, decreased WBC, decreased appetite, decreased neutrophil count, and leukopenia. One patient experienced grade 4 hyponatremia. Preliminary efficacy results showed a disease control rate of 100%, with an overall response rate of 58.3% according to RECIST 1.1. The study concluded that adding a single intratumoral injection of NBTXR3 to weekly low dose cisplatin-containing CCRT was feasible and had a favorable safety profile for patients with LA-HNSCC. A Phase 1b/2 Study Evaluating NBTXR3 in Combination with Concurrent Chemoradiation in the Neoadjuvant Setting for Patients with Locally Advanced or Unresectable Rectal Cancer: This study, sponsored, executed, and presented by PEI, sought to evaluate safety, feasibility, and early signs of efficacy for neoadjuvant NBTXR3 combined with CCRT followed by surgery for patients with locally advanced or unresectable rectal cancer. The study established the recommended phase 2 dose of NBTXR3 at 22% of gross tumor volume, however the phase 2 part of the trial was stopped as a result of the conclusion of the collaboration between PEI and Nanobiotix in 2021. Adult and older patients with T3-T4 locally advanced or unresectable rectal cancer suitable for chemoradiation were eligible for the study and 32 such patients were enrolled. These patients received a single intratumoral injection of NBTXR3, followed by a weekly regimen of CCRT. 31 of 32 patients were deemed evaluable and none of the evaluable patients had tumors eligible for surgery at the time of diagnosis. Of the 31 evaluable patients, 6, 4, 3, and 18 patients received NBTXR3 at the 5%, 10%, 15%, and 22% dose levels, respectively. No NBTXR3-related SAEs or grade greater than or equal to 3 AEs were observed. The most frequently reported AEs were grade 1 or 2 decreased WBC, diarrhea, increased CRP, UTI, and decreased lymphocyte count which were all consistent with what would normally be expected from CCRT. Preliminary efficacy results showed a disease control rate of 100%, with an overall response rate of 35.5% according to RECIST 1.1. Pathological tumor downstaging was observed in 14 of 31 patients after therapy, 25 patients underwent surgery, and 96% of those patients achieved R0 surgical margins. Pathological complete response was observed in 20% of the patients who received surgery. The study concluded that a single intratumoral injection of NBTXR3 in combination with CCRT is feasible and has a favorable safety profile in the neoadjuvant setting for patients with locally advanced or unresectable rectal adenocarcinoma.