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NBTXR3 Activated by Radiotherapy for Patients With Advanced Cancers Treated With An Anti-PD-1 Therapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03589339
Recruitment Status : Recruiting
First Posted : July 17, 2018
Last Update Posted : January 29, 2021
Information provided by (Responsible Party):

Brief Summary:
The 1100 study is an open-label, Phase I, prospective clinical study to assess the safety of intratumoral injection of NBTXR3 activated by radiotherapy in combination with anti-PD-1 therapy.

Condition or disease Intervention/treatment Phase
Radiotherapy Immunotherapy Microsatellite Instability-High Solid Malignant Tumour Metastasis From Malignant Tumor of Stomach (Disorder) Squamous Cell Carcinoma of Head and Neck Metastasis From Malignant Tumor of Cervix Metastatic Squamous Cell Carcinoma Metastasis From Malignant Melanoma of Skin (Disorder) Merkel Cell Carcinoma (Disorder) Metastasis From Malignant Tumor of Lung Metastasis From Malignant Tumor of Bladder (Disorder) Drug: NBTXR3 Phase 1

Detailed Description:
The 1100 study aims to evaluate the safety, efficacy, and tolerability of NBTXR3 activated by radiotherapy in combination with an anti-PD-1 therapy in three cohorts of patients. The first cohort includes patients with LRR or R/M HNSCC with the target lesion in a previously irradiated field. In cohorts two and three, patients present with lung or liver metastases from any primary cancer eligible for anti-PD-1 therapy. These patients have a high unmet need and the Sponsor hypothesizes that NBTXR3 activated by radiotherapy will act synergistically with anti-PD-1 to enhance the therapeutic index of radiotherapy maximizing local effect, to overcome radio-resistance, to increase the local efficacy of immunotherapy, and to improve distant tumor control via an abscopal effect. Eligible patients will receive a single intratumoral injection of NBTXR3 subsequently activated by radiotherapy and then an approved anti-PD-1. The end of treatment visit will take place 4 weeks after the last radiotherapy fraction. Patients will be followed for long-term safety and efficacy until the end of the study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of NBTXR3 Activated by Radiotherapy for Patients With Advanced Cancers Treated With An Anti-PD-1 Therapy
Actual Study Start Date : January 16, 2019
Estimated Primary Completion Date : March 30, 2023
Estimated Study Completion Date : March 30, 2023

Arm Intervention/treatment
Experimental: NBTXR3 activated by SABR Drug: NBTXR3
Single intra Tumoral injection

Primary Outcome Measures :
  1. Determination of the Recommended Dose [ Time Frame: 24 Months ]
    Determination of DLTs, the MTD (if possible), and RP2Ds for each cohort

Secondary Outcome Measures :
  1. Evaluation of the anti-tumor response of R3/RT/PD-1 [ Time Frame: 24 months ]
    Evaluation of the Objective Response Rate: complete or partial response, as defined by RECIST 1.1 and iRECIST

  2. Assessment of the safety and feasibility of R3/RT/PD-1 [ Time Frame: 24 months ]
    Assessment of the number of participants with related late onset toxicities defined as any Grade ≥3 AE occurring after the EOT visit and determination of the number of participants with feasible NBTXR3 intratumoral injection

  3. Evaluation of the body kinetic profile of intratumorally injected NBTXR3 [ Time Frame: 24 months ]
    Evaluation of the time-course dependent accumulation of hafnium in blood and urine following NBTXR3 intratumoral injection

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Signed informed consent form
  • Biopsy-confirmed cancer diagnosis indicated to received anti-PD-1 therapy
  • Has not received prior anti-PD-1 therapy (i.e., anti-PD-1 naïve) or is currently receiving anti-PD-1 therapy and can be considered an anti-PD-1 non-responder (per SITC guidelines)
  • Has at least one tumor lesion that can be accurately measured according to RECIST 1.1. and is amenable for intratumoral injection
  • ECOG performance status 0-2
  • Life expectancy >12 weeks
  • Adequate organ and bone marrow function
  • Negative pregnancy test ≤ 7 days prior to NBTXR3 injection in all female participants of child-bearing potential

Exclusion Criteria:

  • History of severe immune-related adverse events related to administration of anti-PD-1
  • Symptomatic central nervous system metastases and/or carcinomatous meningitis
  • Active autoimmune disease that has required systemic treatment in the past 2 years
  • Known HIV or active hepatitis B/C infection
  • Active infection requiring systemic treatment
  • Received a live virus vaccine within 30 days prior to study treatment
  • History of pneumonitis that required steroids or with current pneumonitis
  • Extensive metastatic disease burden considered to be unamenable for radiation treatment
  • Locoregional recurrent HNSCC with ulceration
  • Has received prior therapy with a checkpoint inhibitor, within 4 weeks prior to NBTXR3 injection
  • Has received prior systemic anti-neoplastic therapy, including investigational agents, within 4 weeks prior to NBTXR3 injection
  • Has not recovered from AEs due to previous anti-neoplastic therapies and/or interventions (including radiation) to ≤ Grade 1 or baseline at screening
  • Clinically significant cardiac arrhythmias
  • Class III or IV Congestive Heart Failure as defined by the New York Heart Association functional classification system < 6 months prior to screening
  • A pregnant or nursing female, or women of child-bearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
  • Any condition for which participation would not be in the best interest of the participant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03589339

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Contact: Katherine JAMESON, PhD +1 (650) 796-9568
Contact: Rodney Carter +1 (617) 460-6609

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United States, Arizona
Banner MD Anderson Cancer Center Recruiting
Gilbert, Arizona, United States, 85234
Contact: Jiaxin Niu, MD, PhD         
The University of Arizona Cancer Center Recruiting
Tucson, Arizona, United States, 85719
Contact: Monstaser Shaheen, MD         
United States, Delaware
Christiana Care Health Services Recruiting
Newark, Delaware, United States, 19713
Contact: Michael Gaurino, MD         
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Jessica Frakes, MD         
United States, Illinois
University of Chicago Medical Center Recruiting
Chicago, Illinois, United States, 60637
Contact: Ari Rosenberg, MD         
United States, Kentucky
University of Louisville, James Graham Brown Cancer Center Recruiting
Louisville, Kentucky, United States, 40202
Contact: Rebecca Redman, MD         
United States, Maryland
Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21287
Contact: Tanguy Seiwert, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Theodore Hong, MD         
United States, New Mexico
Quantum Santa Fe Recruiting
Santa Fe, New Mexico, United States, 87505
Contact: Olivier Rixe, MD         
United States, North Carolina
University of North Carolina, School of Medicine Recruiting
Chapel Hill, North Carolina, United States, 27516
Contact: Colette Shen, MD, PhD         
Sponsors and Collaborators
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Study Director: Elsa Borghi, MD Nanobiotix
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Responsible Party: Nanobiotix Identifier: NCT03589339    
Other Study ID Numbers: 1100
First Posted: July 17, 2018    Key Record Dates
Last Update Posted: January 29, 2021
Last Verified: January 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Nanobiotix:
Oral Cavity Cancer
Oropharynx Cancer
Lung Metastasis
Liver Metastasis
Additional relevant MeSH terms:
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Carcinoma, Merkel Cell
Carcinoma, Squamous Cell
Neoplasm Metastasis
Neoplasms, Second Primary
Squamous Cell Carcinoma of Head and Neck
Stomach Neoplasms
Uterine Cervical Neoplasms
Urinary Bladder Neoplasms
Microsatellite Instability
Pathologic Processes
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms, Squamous Cell
Neoplastic Processes
Polyomavirus Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Carcinoma, Neuroendocrine