NBTXR3 Injected in First Patient With Esophageal Cancer in Phase 1 Study

In the phase 1 clinical trial of NBTXR3 with chemotherapy and radiation therapy as treatment of patients with esophageal cancer, the first patient has been dosed with the investigational tumor-agnostic radioenhancer, announced Nanobiotix in a press release.¹

Now that the first-in-class agent has been dosed in the first study subject, NBTXR3 has been expanded to its seventh potential indication for use as a single agent activated by radiotherapy or in combination with other anti-cancer therapies, including immune checkpoint inhibitors and chemotherapy.

The open-label, single-arm, prospective study (NCT04615013) is a collaborative effort between The University of Texas MD Anderson Cancer Center and Nanobiotix. A total of 24 patients will be enrolled and evaluated for the co-primary end points of the study, which include the incidence of dose-limiting toxicities and the maximum tolerated dose of NBTXR3 in patients with esophageal cancer. Patients in the study will also be assessed for secondary end points, which include the incidence of NBTXR3/radiation therapy–related late-onset toxicities, the feasibility of NBTXR3 injection in the esophageal tumor and involved regional lymph nodes, objective response rate, major pathological response rate, local progression-free survival (PFS), distant PFS, PFS, and overall survival.

“We believe that NBTXR3 could have a positive impact for patients with cancer in any case where radiotherapy is a part of the standard of care. Expansion into esophageal cancer represents not only another step toward achieving our goals, it also highlights the ongoing progress of our clinical collaboration agreement with The University of Texas MD Anderson Cancer Center,” said Laurent Levy, CEO, Nanobiotix, in a statement.

The rationale for the phase 1 study of NBTXR3 comes from preclinical studies presented during the Society for Immunotherapy of Cancer (SITC) Annual Meeting, which showed thatNBTXR3 led to an abscopal effect when activated by radiotherapy and without combination with an immune checkpoint inhibitor. NBTXR3 with radiotherapy also prompted adaptive antitumor immunity and multiplied T-cell receptor repertoire diversity in treated tumors when compared with radiotherapy alone.²

Disease control was also achieved with NBTXR3 activated by radiotherapy regardless of whether the radiation was low dose or high dose, and when combined with an anti-PD-1 and anti-CTLA-4 therapy, there was a significant improvement in the control of primary and secondary tumors, as well as prolonged survival. A reduction in lung metastases was also observed in an anti-PD-1 resistant lung cancer model.

When combined with an immune checkpoint inhibitor in the preclinical setting, NBTXR3 achieved both molecular and cellular responses in addition to long-term antitumor memory.

Aside from tumor models, NBTXR3 has shown promise as treatment of patients with rectal cancer when activated by radiotherapy and in combination concurrent chemotherapy, according to findings from a phase 1B/2 study (NCT02465593). Topline results presented during the 2021 American Society of Clinical Oncology Gastrointestinal Cancers Symposium showed that the agent was well-tolerated across all dose levels administered and led to no adverse events (AEs), or serious AEs. One patient in the study did experience s dose-limiting toxicity of urinary tract infection that investigators determined was caused by the injection procedure. Of the AEs that were observed in the study, the most frequent included (~45%), leukopenia (~40%), and dermatitis (~25%). All AEs observed were grades 1 or 2.³

In terms of efficacy in rectal cancer, NBTXR3 led to objective tumor responses in over 70% of patients after concurrent chemoradiation.

The study of NBTXR3 in esophageal cancer is split into 2 parts. Part 1 of the study is the dose-escalation phase, which is meant to determine the recommended phase 2 dose (RP2D) of NBTXR3 activated by radiotherapy with concurrent chemotherapy. In part 2, the study will be expanded to monitor toxicity at the RP2D of the agent with radiotherapy and chemotherapy.¹

To be eligible for enrollment in the trial, patients are required to be aged 18 years or older with stage II-III adenocarcinoma of the esophagus that are treatment naïve and radiographically non-metastatic at the time of screening. Patients must be eligible to receive chemotherapy of either oxaliplatin, docetaxel, or carboplatin plus paclitaxel. Patients must also be able to undergo endoscopic ultrasound-guided injection of NBTXR3. In terms of disease characteristics, eligible patients are those with at least 1 measurable lesion with a maximum of 4 measurable lesions, an ECOG performance status of 0 to 2, and adequate laboratory values.

Currently, the trial is still recruiting patients with esophageal cancer. The recruitment period will last up to 24 months.

_Reference:

_{1. Nanobiotix announces first patient injected with nbtxr3 in esophageal cancer. News release. Nanobiotix. January 28, 2021. Accessed February 2, 2021. https://bit.ly/3as6mT9}

_{2. Nanobiotix announces positive new pre-clinical data suggesting radioenhancer NBTXR3 could have a significant impact in immunotherapy. News release. Nanobiotix. November 12, 2020. Accessed February 2, 2021. https://bit.ly/3pTELk0}

_{3. Nanobiotix announces positive first results for novel NBTXR3 in rectal cancer study at ASCO-GI 2021. News release. Nanbiotix. January 15, 2021. Accessed February 2, 2021. https://bit.ly/3oGa1Su}