Phase I/II Randomized Study of NBTXR3 Activated by Abscopal or RadScopal Radiation in Combination With Immunotherapy (Anti-PD-1/L-1) for Patients With Advanced Solid Malignancies

NCT05039632 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2020-0618NCI-2021-09077
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and possible benefits of NBTXR3, radiation therapy, Anti PD-1 / PD-L1 in treating patients with solid tumor that has spread to the lung (lung metastases) and/or liver (liver metastases). NBTXR3 may help make tumor cells more sensitive to the radiation therapy. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Immunotherapy with Anti PD-1 / PD-L1 monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving NBTXR3, radiation therapy, Anti PD-1 / PD-L1 may help to control the disease.

Conditions

Advanced Malignant Solid Neoplasm; Metastatic Malignant Neoplasm in the Liver; Metastatic Malignant Neoplasm in the Lung; Metastatic Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (2)

• Incidence of dose limiting toxicities

  Descriptive summary tables will be produced.

  Up to 4 weeks post radiation therapy

• Objective response rate

  Defined as percentage of patients achieving complete or partial response, per immune-related Response Evaluation Criteria In Solid Tumors (irRECIST). The best overall response will be provided per irRECIST criteria and consideration of all imaging assessment is required.

  Up to 12 weeks post radiation therapy

Study Arms (2)

Cohort I (NBTXR3, Abscopal, Anti PD-1 / PD-L1

EXPERIMENTAL

COHORT I: Patients receive NBTXR3 intratumorally on day 1. Patients also receive ( anti-PD-1/L-1) intravenously (IV) on day 8. Beginning day 15, patients undergo Abscopal radiation therapy over 1-2 weeks. Cycles with ( anti-PD-1/L-1) repeat every 3-6 weeks per standard of care up to 2 years in the absence of disease progression or unacceptable toxicity.

Other: Hafnium Oxide-containing Nanoparticles NBTXR3; Radiation: Radiation Therapy

Cohort II (NBTXR3, RadScopal, Anti PD-1 / PD-L1

EXPERIMENTAL

COHORT II: Patients receive NBTXR3 intratumorally on day 1. Patients also receive ( anti-PD-1/L-1) IV on day 8. Beginning day 15, patients undergo RadScopal radiation therapy over 1-2 weeks. Cycles with ( anti-PD-1/L-1)repeat every 3-6 weeks per standard of care up to 2 years in the absence of disease progression or unacceptable toxicity.

Other: Hafnium Oxide-containing Nanoparticles NBTXR3; Radiation: Radiation Therapy

Interventions

Hafnium Oxide-containing Nanoparticles NBTXR3 OTHER

Given intratumorally

Also known as: NBTXR3

Cohort I (NBTXR3, Abscopal, Anti PD-1 / PD-L1; Cohort II (NBTXR3, RadScopal, Anti PD-1 / PD-L1

Radiation Therapy RADIATION

Undergo Abscopal radiation therapy

Also known as: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Cohort I (NBTXR3, Abscopal, Anti PD-1 / PD-L1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with metastatic disease in the lung and/or liver, or soft tissue from any primary malignancy considered incurable by local therapies.
• a. One prior anti-PD-1/L1 therapy allowed.
• The target lesion(s) must be measurable as per irRECIST and repeated measurements at the same anatomical location should be achievable.
• a. Participant must have at least 2 measurable lesions at screening. i. Abscopal cohort: At least one lesion will receive NBTXR3 and high dose radiation (high dose target lesion). The other lesion(s) (non-treated target lesion) will be followed for response and it will not receive NBTXR3 or RT.
• ii. RadScopal™ cohort: At least one lesion will receive NBTXR3 and high dose radiation (high dose target lesion). The other lesion(s) will only receive low dose radiation (low dose target lesion).
• Amenable to undergo the image guided (EBUS or CT or MRI) intratumoral injection of NBTXR3, in up to two (2) high dose target lesions, as determined by the investigator or treating physician at screening.
• a. Intratumoral NBTXR3 injections only allowed in lung or liver lesions.
• Selected high and low dose target lesions must be amenable to receive radiation therapy as determined by the investigator or treating radiation oncologist.
• Allowed high dose RT regimens are 50 Gy in 4 fractions or 60 Gy in 10 fractions
• Allowed low dose RT for RadScopal™ cohort is 1.4 Gy per fraction for 4 - 5 fractions to only low dose-target lesion(s) determined by the investigator or treating physician.
• Patients can receive radiation therapy for symptomatic metastatic disease prior to enrollment or during the study a.
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• Laboratory Values at screening:
• Hemoglobin ≥ 9.0 g/dL

You may not qualify if:

• Prior radiation therapy received to the selected high dose target lesion(s)
• a. Previous radiation to low dose target lesions allowed as per investigator or treating radiation oncologist discretion.
• Symptomatic central nervous system metastases and/or carcinomatous meningitis
• a. Participants with previously treated brain metastases may participate if those lesions are radiologically stable (i.e., without evidence of progression for at least 4 weeks by repeat imaging at screening), clinically stable, and without requirement of steroid treatment for at least 14 days prior to NBTXR3 injection.
• At screening, past medical history of:
• Interstitial lung disease
• Unresolved organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia)
• Any Grade 4 radiation toxicity
• Unresolved, radiation or ICI related
• i. Pneumonitis ii. Bronchopulmonary hemorrhage iii. Abdominal hemorrhage e. Unresolved GI related events i. Diverticulitis ii. Colitis iii. Intra-abdominal abscess iv. GI obstructions v. Abdominal carcinomatosis vi. Any known risk factor for bowel perforation
• History of severe (Grade ≥ 3) immune-related adverse events observed with previous immunotherapy (anti-PD-1/L1) or known sensitivity (Grade ≥ 3) to any excipients.
• Has received any approved or investigational anti-neoplastic agent or immunotherapy within 2 weeks prior to NBTXR3 injection.
• Except anti-PD-1/L1, which will not require a washout window.
• A reduced washout window may be considered for therapies with short half-lives (i.e., kinase inhibitors) after discussion with Nanobiotix and investigator.
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena

Study Officials

• Saumil Gandhi, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nathan Comeaux

CONTACT

832-728-0689; nicomeaux@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2021
• First Posted: September 9, 2021
• Study Start: May 8, 2023
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028
• Last Updated: February 6, 2026

Record last verified: 2026-02

Locations

US (1)