On November 14, 2022 NANOBIOTIX (Euronext : NANO –– NASDAQ: NBTX – the ‘‘Company’’), a late-clinical stage biotechnology company pioneering physics-based approaches to expand treatment possibilities for patients with cancer, reported completion of the dose escalation part of a phase 1 dose escalation and dose expansion study evaluating potential first-in-class radioenhancer NBTXR3 for patients with locally advanced (LA) or borderline resectable (BR) pancreatic cancer (PC) (Press release, Nanobiotix, NOV 14, 2022, View Source [SID1234624006]). The phase 1 study ("Study 2019-1001") is being conducted by The University of Texas MD Anderson Cancer Center (MD Anderson).
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"The tolerable safety profile, establishment of recommended phase 2 dose, and early signals of efficacy we have observed in the dose escalation part for locally advanced patients of our phase 1 study give us confidence to now include borderline resectable patients in the expansion part," said Leonard A. Farber, MD, Chief Clinical and Medical Affairs Officer at Nanobiotix. "In the borderline resectable pancreatic cancer population, a positive correlation has been observed between achieving resectability through local and systemic control with preoperative therapy and potentially improving survival outcomes. Inclusion of the borderline resectable stage in the study will also expand the eligible patient population to include a larger proportion of pancreatic cancer patients, allowing for the robust evaluation of NBTXR3’s potential to have a significant impact in this recalcitrant disease."
Study 2019-1001 is being conducted as part of the ongoing strategic collaboration between Nanobiotix and MD Anderson. The complete dose escalation part of the study recruited 11 patients, and all patients had unresectable disease at study entry. A single intratumoral injection of NBTXR3 followed by 15 fractions of RT showed to be feasible and well-tolerated and the recommended phase 2 dose of NBTXR3 was established at 42% of gross tumor volume.
Notably, one patient on Study 2019-1001 had a partial response 9 months after RT and has had durable local control for over two years. One other patient experienced local control that allowed unresectable disease to become resectable. Negative margin surgery ("R0 surgery") was achieved for this patient and pathological complete response was observed. The dose expansion part of the study will include more robust evaluation of patients with borderline resectable disease at study entry.
About Study 2019-1001
Pancreatic cancer (PC) is a rare, deadly disease. Given that surgery with R0 resection (i.e., macroscopically complete tumor removal with negative microscopic surgical margins) remains the only hope for long-term survival, clinical trials have investigated various neoadjuvant strategies—wherein patients receive anti-cancer drugs or radiation prior to surgery—to increase the surgery-eligible population while also increasing the R0 resection rate.
MD Anderson Study 2019-1001 is an open-label, single-arm, prospective phase I study consisting of two parts: (i) dose-escalation to determine the recommended phase 2 dose (RP2D); and (ii) expansion at RP2D.
The patient population will include adults (age ≥ 18 years) with borderline resectable (BR) or locally advanced (LA) PC that are radiographically non-metastatic at screening, and that have not previously received radiation therapy or surgery for pancreatic cancer. The complete dose escalation part recruited 11 patients with unresectable LAPC and the RP2D was established at 42% of gross tumor volume. Twelve additional patients with either LAPC or BRPC will be enrolled for the RP2D expansion.
The objectives of the study are the determination of dose-limiting toxicity (DLT), the maximum tolerated dose (MTD), and the RP2D.
About NBTXR3
NBTXR3 is a novel, potentially first-in-class oncology product composed of functionalized hafnium oxide nanoparticles that is administered via one-time intratumoral injection and activated by radiotherapy. The product candidate’s physical 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, Nanobiotix believes that NBTXR3 could be scalable across any solid tumor that can be treated with radiotherapy and across any therapeutic combination, particularly immune checkpoint inhibitors.
NBTXR3 is being evaluated in locally advanced head and neck squamous cell carcinoma (HNSCC) as the primary development pathway. The company-sponsored phase I dose escalation and dose expansion study has produced favorable safety data and early signs of efficacy; and a phase III global registrational study was launched in 2021. In February 2020, the United States Food and Drug Administration 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 III study.
Nanobiotix has also prioritized an Immuno-Oncology development program—beginning with a Company-sponsored phase I clinical study evaluating NBTXR3 activated by radiotherapy in combination with anti-PD-1 checkpoint inhibitors for patients with locoregional recurrent or recurrent/metastatic HNSCC, or lung or liver metastases from any primary cancer eligible for anti-PD-1 therapy.
Given the Company’s focus areas, and balanced against the scalable potential of NBTXR3, Nanobiotix has engaged in a strategic collaboration strategy with world class partners to expand development of the product candidate in parallel with its priority development pathways. Pursuant to this strategy, in 2019 Nanobiotix entered into a broad, comprehensive clinical research collaboration with The University of Texas MD Anderson Cancer Center to sponsor several phase I and phase II studies to evaluate NBTXR3 across tumor types and therapeutic combinations.