RECRUITING

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

Conditions

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2023-05-08

Study Completion:2026-02-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05039632

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Patients with metastatic disease in the lung and/or liver, or soft tissue from any primary malignancy considered incurable by local therapies. 2. The target lesion(s) must be measurable as per irRECIST and repeated measurements at the same anatomical location should be achievable. 3. 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. 4. Selected high and low dose target lesions must be amenable to receive radiation therapy as determined by the investigator or treating radiation oncologist. 1. Allowed high dose RT regimens are 50 Gy in 4 fractions or 60 Gy in 10 fractions 2. 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. 5. Patients can receive radiation therapy for symptomatic metastatic disease prior to enrollment or during the study a. 6. Age ≥ 18 years 7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 8. Laboratory Values at screening: 1. Hemoglobin ≥ 9.0 g/dL 2. Absolute Neutrophil Count (ANC) ≥ 1,500/mm3 3. Platelet count ≥ 100,000/mm3 4. Leukocytes ≥ 1500/mm3 5. Creatinine ≤ 1.5 x upper limit of normal (ULN) 6. Calc. creatinine clearance \> 30mL/min 7. Total bilirubin ≤ 2.0 mg/dL 8. AST / ALT ≤ 2.0 x upper limit of normal (ULN) or ≤ 3 x ULN for patients with liver metastases 9. For patients with lung metastases, adequate lung function with expiratory volume in 1 second (FEV1) ≥ 0.8L or ≥ 35% predicted and carbon monoxide diffusing capability (DLCO) ≥ 40% with or without bronchodilator within 30 days prior to NBTXR3 injection. 10. Patients who meet the criterion above without oxygen (02), but need acute (started within 7 ± 3 days) supplemental oxygen due to tumor-caused obstruction/hypoxia are eligible, provided the amount of the O2 needed has been stable. 11. Negative urine or serum pregnancy test ≤ 7 days prior to NBTXR3 injection in all women of child-bearing potential (WOCBP). WOCBP must agree to follow instructions for method(s) of contraception for the duration the entire study period and 160 days (\~5.33 months) after the last dose of anti-PD-1/L-1 treatment. Local laws and regulations may require use of alternative and/or additional contraception methods. WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements but should still undergo pregnancy testing. 12. Signed informed consent form (ICF) indicating that participant understands the purpose of, and procedures required for, the study and is willing to participate in the study. 4.2	1. Prior radiation therapy received to the selected high dose target lesion(s) 2. Symptomatic central nervous system metastases and/or carcinomatous meningitis 3. At screening, past medical history of: 1. Interstitial lung disease 2. Unresolved organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia) 3. Any Grade 4 radiation toxicity 4. Unresolved, radiation or ICI related 4. 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. 5. Has received any approved or investigational anti-neoplastic agent or immunotherapy within 2 weeks prior to NBTXR3 injection. 1. Except anti-PD-1/L1, which will not require a washout window. 2. A reduced washout window may be considered for therapies with short half-lives (i.e., kinase inhibitors) after discussion with Nanobiotix and investigator. 6. 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). 7. Any live-virus vaccine used for prevention of infectious diseases administered within 4 weeks prior to NBTXR3 injection. 1. Except killed-virus Influenza vaccine 2. Exception of other vaccines (e.g. pneumonia) is at the discretion of the treating physician after conducting a personalized risk assessment on a case by case basis. 8. Prior allogenic stem cell transplantation or organ allograft. 9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, renal failure, cardiac arrhythmia, or psychiatric illness that would limit compliance with treatment. 10. Known active, uncontrolled (high viral load) HIV or hepatitis B or hepatitis C infection. 11. Female patients who are pregnant or breastfeeding. 12. Women of child-bearing potential and their male partners who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and up to 160 days (\~5.33 months) for female participants, and 7 months for males participants or female partners of male participants that are of child-bearing potential, after the last dose of anti-PD-1/L-1. 13. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.

Inclusion Criteria

Exclusion Criteria

1. Patients with metastatic disease in the lung and/or liver, or soft tissue from any primary malignancy considered incurable by local therapies.
2. The target lesion(s) must be measurable as per irRECIST and repeated measurements at the same anatomical location should be achievable.
3. 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.
4. Selected high and low dose target lesions must be amenable to receive radiation therapy as determined by the investigator or treating radiation oncologist.
1. Allowed high dose RT regimens are 50 Gy in 4 fractions or 60 Gy in 10 fractions
2. 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.
5. Patients can receive radiation therapy for symptomatic metastatic disease prior to enrollment or during the study a.
6. Age ≥ 18 years
7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
8. Laboratory Values at screening:
1. Hemoglobin ≥ 9.0 g/dL
2. Absolute Neutrophil Count (ANC) ≥ 1,500/mm3
3. Platelet count ≥ 100,000/mm3
4. Leukocytes ≥ 1500/mm3
5. Creatinine ≤ 1.5 x upper limit of normal (ULN)
6. Calc. creatinine clearance \> 30mL/min
7. Total bilirubin ≤ 2.0 mg/dL
8. AST / ALT ≤ 2.0 x upper limit of normal (ULN) or ≤ 3 x ULN for patients with liver metastases
9. For patients with lung metastases, adequate lung function with expiratory volume in 1 second (FEV1) ≥ 0.8L or ≥ 35% predicted and carbon monoxide diffusing capability (DLCO) ≥ 40% with or without bronchodilator within 30 days prior to NBTXR3 injection.
10. Patients who meet the criterion above without oxygen (02), but need acute (started within 7 ± 3 days) supplemental oxygen due to tumor-caused obstruction/hypoxia are eligible, provided the amount of the O2 needed has been stable.
11. Negative urine or serum pregnancy test ≤ 7 days prior to NBTXR3 injection in all women of child-bearing potential (WOCBP). WOCBP must agree to follow instructions for method(s) of contraception for the duration the entire study period and 160 days (\~5.33 months) after the last dose of anti-PD-1/L-1 treatment. Local laws and regulations may require use of alternative and/or additional contraception methods. WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements but should still undergo pregnancy testing.
12. Signed informed consent form (ICF) indicating that participant understands the purpose of, and procedures required for, the study and is willing to participate in the study.
4.2

1. Prior radiation therapy received to the selected high dose target lesion(s)
2. Symptomatic central nervous system metastases and/or carcinomatous meningitis
3. At screening, past medical history of:
1. Interstitial lung disease
2. Unresolved organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia)
3. Any Grade 4 radiation toxicity
4. Unresolved, radiation or ICI related
4. 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.
5. Has received any approved or investigational anti-neoplastic agent or immunotherapy within 2 weeks prior to NBTXR3 injection.
1. Except anti-PD-1/L1, which will not require a washout window.
2. A reduced washout window may be considered for therapies with short half-lives (i.e., kinase inhibitors) after discussion with Nanobiotix and investigator.
6. 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).
7. Any live-virus vaccine used for prevention of infectious diseases administered within 4 weeks prior to NBTXR3 injection.
1. Except killed-virus Influenza vaccine
2. Exception of other vaccines (e.g. pneumonia) is at the discretion of the treating physician after conducting a personalized risk assessment on a case by case basis.
8. Prior allogenic stem cell transplantation or organ allograft.
9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, renal failure, cardiac arrhythmia, or psychiatric illness that would limit compliance with treatment.
10. Known active, uncontrolled (high viral load) HIV or hepatitis B or hepatitis C infection.
11. Female patients who are pregnant or breastfeeding.
12. Women of child-bearing potential and their male partners who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and up to 160 days (\~5.33 months) for female participants, and 7 months for males participants or female partners of male participants that are of child-bearing potential, after the last dose of anti-PD-1/L-1.
13. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.

Contacts and Locations

Study Contact

Nathan Comeaux

CONTACT

832-728-0689

nicomeaux@mdanderson.org

Principal Investigator

Saumil Gandhi, MD

PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Study Locations (Sites)

M D Anderson Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: M.D. Anderson Cancer Center

Saumil Gandhi, MD, PRINCIPAL_INVESTIGATOR, M.D. Anderson Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-05-08

Study Completion Date2026-02-01

Study Record Updates

Study Start Date2023-05-08

Study Completion Date2026-02-01

Terms related to this study

Additional Relevant MeSH Terms

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