Abstract 207P
Background
ReRT of inoperable locally recurrent NSCLC after prior radiotherapy (RT) 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. This study aimed to determine the safety, feasibility, and recommended phase II dose (RP2D) of intra-tumoral NBTXR3 with reRT.
Methods
Bayesian optimal interval design was used to escalate NBTXR3 dose. Patients (Pts) with Stage IA-IV biopsy proven recurrent NSCLC within prior RT field were eligible. Pts with history of RT within prior 6 months, grade (G) 4 RT toxicity, or interstitial lung disease were excluded. Pts received RT after NBTXR3 intra-tumoral injection at dose of 22% or 33% of gross tumor volume (GTV) based on the RT planning CT scan. Up to 4 sites were allowed to be injected with NBTXR3. RT dose was 45 Gy in 15 fractions. 30 Gy in 10 fractions was permitted per physician discretion to meet protocol organ at risk constraints. Dose limiting toxicities (DLTs) were defined as any CTCAE v5.0 G3+ adverse events (AEs) related to NBTXR3 or RT within 2 months of NBTXR3 injection. Local progression free survival (LPFS) was estimated by the Kaplan Meier method.
Results
From 2022 to 2023, 12 pts (median age 71 years, range 47–91) were enrolled. 14 sites were injected and treated (2 sites in 2 pts): 3 mediastinal lymph nodes and 11 lung lesions (10 central, 1 peripheral). NBTXR3was injected bronchoscopically (n=10) or by CT guidance (n=4). Median GTV was 16 mL (range 3–157). Median NBTXR3 volume was 5 mL (range 1–51). 3 pts received NBTXR3 dose of 22%; 9 received NBTXR3 dose of 33%. All 12 pts completed treatment with NBTXR3 plus reRT without DLTs. Maximum tolerated dose was not reached. NBTXR3 RP2D was 33% of GTV. At 14.7 months median follow-up, RT-related AEs were: G5 respiratory failure (6 months after RT, possibly related); G3: dyspnea (n=2), lymphopenia (n=1), hypotension (n=1), tachycardia (n=1). There were no G3-5 NBTXR3/injection related AEs. 1-year LPFS was 64%. Median LPFS was 18.6 months.
Conclusions
NBTXR3 plus reRT is feasible and safe for locally recurrent NSCLC. RP2D of 33% will be used in an ongoing dose expansion phase.
Clinical trial identification
NCT04505267.
Legal entity responsible for the study
The authors.
Funding
Nanobiotix.
Disclosure
S. Gandhi: Financial Interests, Personal, Research Grant: BMS, Nanobiotix, BMS Foundation; Financial Interests, Personal, Other: AstraZeneca. A. Chen: Financial Interests, Personal, Research Grant: Blue Halo, Proteus Consortium/Pfizer, Novocure. S. Chun: Financial Interests, Personal, Research Grant: National Institutes for Health; Financial Interests, Personal, Advisory Role: AstraZeneca, CurioScience, Norton Healthcare; Financial Interests, Personal, Other: Binaytara Foundation, ViewRay, AstraZeneca. S.H. Lin: Financial Interests, Personal, Other, Consultant: XRAD Therapeutics; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Varian Medical Systems; Financial Interests, Personal, Full or part-time Employment: The University of Texas MD Anderson Cancer Center; Financial Interests, Personal, Ownership Interest, Co-Founder and Scientific Advisor: Seek Diagnostics; Financial Interests, Personal, Research Grant: STCube Pharmaceuticals, Beyond Spring Pharmaceuticals; Financial Interests, Personal, Funding: Nektar Therapeutics; Non-Financial Interests, Personal, Leadership Role, Co-Chair RTDT Committee: NRG Oncology. J.Y. Chang: Financial Interests, Institutional, Research Grant: Siemens-MDACC Alliance, AstraZeneca, NCI NIH SORT Study, BMS-MDACC Research Alliance; Financial Interests, Personal, Advisory Role: Regeneron; Financial Interests, Personal, Other: Varian, Ion Beam Applications; Financial Interests, Personal, Leadership Role: PTCOG; Financial Interests, Personal, Member of Board of Directors: IASLC. J.W. Welsh: Financial Interests, Personal, Funding: Nanobiotix; Financial Interests, Personal, Advisory Role: Kezar Lifescience, Reflexion, Alpine Immune Sciences; Financial Interests, Personal, Stocks/Shares: Nanorobotics, Oncoresponse, Checkmate Pharmaceuticals, Molecular Match; Financial Interests, Personal, Research Grant: Novocure, Takeda, Varian, Bayer Healthcare, Pebble Life Science; Financial Interests, Personal, Other: Taiwan Lung Cancer Society; Financial Interests, Personal, Principal Investigator: Kiromic, Gilead, Hotspot Therapeutics, Artidis, BMS, Sciclone; Financial Interests, Personal, Leadership Role: Oligo Immune; Financial Interests, Personal, Ownership Interest: DV8. Z. Liao: Financial Interests, Personal, Research Grant: National Institutes for Health, National Cancer Institute. R. Casal: Financial Interests, Personal, Other: Siemens, Canon, Intuitive Surgical, Johnson & Johnson. All other authors have declared no conflicts of interest.