1631P - Phase I study of endoscopic ultrasound (EUS)-guided NBTXR3 delivery activated by radiotherapy (RT) for locally advanced or borderline resectable pancreatic cancer (LAPC or BRPC)

Background

Patients with LAPC or BRPC often receive RT after chemotherapy (chemo) if no metastatic progression has occurred, and CA19-9 historically normalizes ∼20% after all therapy. While escalated dose RT (EDR) has shown promising survival in selected patients, RT dose limitations of the bowel often prevent safe EDR. To overcome this challenge, we are investigating NBTXR3, a functionalized hafnium oxide radio enhancer administered by a single intratumoral injection, locally amplifying the RT dose. The primary objective is to determine NBTXR3 recommended phase II dose (RP2D) and secondary objective is to measure anti-tumor effects.

Methods

The study uses a Bayesian optimal interval design (BOIN) with two parts: dose-finding for RP2D (NBTXR3 at [level 1] 33% of gross tumor volume [GTV] or [level 2] at 42% of GTV) and cohort expansion at RP2D. In part 1, eligibility criteria included only LAPC patients with no evidence of metastatic disease after 2-6 months of chemo, part 2 allows BRPC. NBTXR3 is given once prior to RT via EUS-guided intratumoral injection. All patients receive 45 Gy in 15 fractions to GTV. Target tumor response is per RECIST v1.1 criteria. CA19-9 is measured serially.

Results

As of January 12, 2023, 12 LAPC patients (median age 61 years [range 43-81], 8 males, 4 females) received protocol therapy. The first patient (level 1) and subsequent 11 patients (level 2) had no dose limiting toxicities (DLTs). At 4 weeks post RT, 11 had stable disease (SD) locally (1 had progressive disease [PD] overall) and 1 had radiographic complete response (CR). At 3 months post RT, 11 had SD locally (1 PD overall), and 1 had surgery with negative margins and no residual viable tumor. 6 patients had elevated CA19-9 before NBTXR3/RT, 5 of these 6 (83%) had a decrease in CA19-9 subsequently, and 2 of these 6 (33%) had CA19-9 normalization eventually. 9 patients had elevated CA19-9 at diagnosis, and 5 out of 9 patients (56%) had normalization of CA19-9 after all therapy.

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.

Clinical trial identification

2019-1001, start date: July 1, 2020.

Editorial acknowledgement

Legal entity responsible for the study

The University of Texas MD Anderson Cancer Center.

Funding

The University of Texas MD Anderson Cancer Center, Nanobiotix.

Disclosure

M.H. Katz: Financial Interests, Advisory Role: Alcresta Therapeutics, AbbVie, Nestle health science, Taiho Oncology. C.D. Tzeng: Financial Interests, Advisory Role: Ethicon/Johnson & Johnson; Financial Interests, Other, Honoraria: PanTher Therapeutics. M.J. Overman: Financial Interests, Advisory Role: Bristol Myers Squibb, Roche/Genentech, Gritstone Bio, MedImmune, Novartis, Promega, Spectrum Pharmaceuticals, Array BioPharma, Janssen, Pfizer, 3D Medicines, Merck, Eisai; Financial Interests, Research Funding: Bristol Myers Squibb, Merck, Roche, MedImmune. S. Pant: Financial Interests, Advisory Role: Zymeworks, Ipsen, Novartis, Janssen; Financial Interests, Institutional, Research Funding: Mirati Therapeutics, Lilly, Xencor, Novartis, Rgenix, Bristol Myers Squibb, Astellas Pharma, Purple Biotech, 4D Pharma, Boehringer Ingelheim, NGM Biopharmaceuticals, Janssen, Arcus Biosciences, Elicio Therapeutics, Biontech, Ipsen, Zymeworks, Pfizer. M.S. Lee: Financial Interests, Personal, Advisory Role: Pfizer, Imvax, G1 Therapeutics, Delcath Systems, Bayer Health; Financial Interests, Institutional, Research Funding: Arcus Biosciences, Erasca, Inc, Repare Therapeutics, Merck, TriSalus Life Sciences, Boehringer Ingelheim, Xilis, EpimAb BioTherapeutics. R. wolff: Financial Interests, Personal, Royalties: McGraw-Hill: Editor: M.D. Anderson Manual of Medical Oncology, 3rd edition; Other, Other, Honoraria: Emirates Oncology Society, Emirates Oncology Society. M. Javle: Financial Interests, Personal, Advisory Board: QED, Taiho, Merck, Transthera, Incyte, Servier, AstraZeneca; Financial Interests, Personal, Steering Committee Member: Oncosil, Incyte; Non-Financial Interests, Principal Investigator: QED, Basilea. C.M. Taniguchi: Financial Interests, Personal, Other, Honoraria: Xerient; Financial Interests, Personal, Advisory Role: Accuray, Xerient, Phebra; Financial Interests, Personal, Royalties: Oral amifostine for radio protection of the intestinal tract, PHD inhibitors for radio protection of the GI tract . E.B. Ludmir: Other, Full or part-time Employment, An Immediate Family Member: Zymeworks. P. Das: Other, Personal, Other, Honoraria: Bayer, Imedex, Physicans' Education Resource. A.C. Koong: Financial Interests, Personal, Stocks or ownership: Aravive. O.I. Vivar: Financial Interests, Personal, Full or part-time Employment: Nanobiotix. E.P. Tamm: Financial Interests, Other, Travel, Accommodations, Expenses: Siemens Healthineers, GE Healthcare; Financial Interests, Institutional, Research Funding: GE Healthcare. M.S. Bhutani: Financial Interests, Personal, Other, Consultant: Oncosil, Starpax; Financial Interests, Institutional, Research Grant: Nanobiotix, Augmenix. E.J. Koay: Financial Interests, Other, Honoraria: Apollo; Financial Interests, Advisory Role: Augmenix, RenovoRx, AstraZeneca Co., IO Life Science; Financial Interests, Speaker’s Bureau: Oncology Information Group; Financial Interests, Research Funding: Elekta, GE Healthcare, Philips Healthcare, ARTIDIS; Financial Interests, Royalties: Provisional patent on 3D printed oral stents for radiation treatments of head and neck cancer, Royalties from Taylor and Francis LLC for my co-authored book: An introduction to physical oncology All other authors have declared no conflicts of interest.