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Trial record 1 of 1 for:    NCT03589339
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NBTXR3 Activated by Radiotherapy for Patients With Advanced Cancers Treated With An Anti-PD-1 Therapy

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ClinicalTrials.gov Identifier: NCT03589339
Recruitment Status : Recruiting
First Posted : July 17, 2018
Last Update Posted : June 24, 2022
Sponsor:
Information provided by (Responsible Party):
Nanobiotix

Brief Summary:
The 1100 study is an open-label, Phase I, dose escalation and expansion 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 Liver Squamous Cell Carcinoma of Head and Neck Metastasis From Malignant Tumor of Cervix Metastatic Renal Cell Carcinoma Metastasis From Malignant Melanoma of Skin (Disorder) Metastatic Triple-Negative Breast Carcinoma Metastatic NSCLC Metastasis From Malignant Tumor of Bladder (Disorder) Drug: NBTXR3 Radiation: SABR Drug: Nivolumab Drug: Pembrolizumab 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 in dose escalation and expansion parts. The Escalation Cohort 1 includes patients with LRR or R/M HNSCC with the injectable lesion in a previously irradiated field. In Escalation Cohorts 2 and 3, patients present with lung or liver metastases from any primary cancer eligible for anti-PD-1 therapy.

The Expansion cohort 1 includes patients with LRR or R/M HNSCC with the injectable lesion located either in head and neck area or in lung or liver, who are resistant to anti-PD-1 therapy. The Expansion cohort 2 includes patients with LRR or R/M HNSCC with the injectable lesion located either in head and neck area or in lung or liver, who are naive to anti-PD-1 therapy.

The Expansion Cohort 3 includes patients with inoperable NSCLC, malignant melanoma, HCC, RCC, urothelial cancer, cervical cancer or TNBC with metastases to lungs, liver or soft tissue and who are resistant to 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 for 2 years after the EOT visit.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 145 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Dose Escalation / Dose Expansion 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 : May 30, 2028


Arm Intervention/treatment
Experimental: NBTXR3 activated by SABR followed by anti-PD-1 monotherapy
Intratumoral injection of NBTXR3 followed by SABR followed by monotherapy with nivolumab or pembrolizumab
Drug: NBTXR3
Single intra Tumoral injection

Radiation: SABR
Radiotherapy given as a definite number of fractions at the dose defined for each radiation field
Other Names:
  • Stereotaxic Ablative Radiotherapy
  • Stereotaxic Body Radiation Therapy

Drug: Nivolumab
Anti-PD-1 monotherapy
Other Name: Opdivo

Drug: Pembrolizumab
Anti-PD-1 monotherapy
Other Name: Keytruda




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
Criteria

Inclusion Criteria:

  • Signed informed consent form
  • Biopsy-confirmed cancer diagnosis indicated to receive anti-PD-1 therapy:

Dose Escalation:

  1. Escalation Cohort 1: Is inoperable LRR with tumor in previously irradiated HN field that is amenable to re-irradiation or R/M HNSCC with tumor in previously irradiated HN field that is amenable to re-irradiation, or
  2. Escalation Cohort 2: Has metastasized to the lung (including involved lymph nodes) with tumor in a previously non-irradiated lung field, or
  3. Escalation Cohort 3: Has metastasized to the liver with tumor in a previously non-irradiated liver field

Expansion:

  1. Expansion Cohorts 1 and 2: Is inoperable LRR or R/M HNSCC with at least one lesion that is amenable to irradiation within head and neck region, lung or liver
  2. Expansion Cohort 3: Is inoperable NSCLC, malignant melanoma, HCC, RCC, urothelial cancer, cervical cancer, TNBC that has metastasized to soft tissues, lung (including mediastinal lymph nodes) or liver with at least one lesion that is amenable to irradiation

    • Prior anti-PD-1 exposure as follows:

Dose Escalation (all cohorts):

  1. Has not received prior anti-PD-1 therapy (i.e., anti-PD-1 naïve), or
  2. Has received prior anti-PD-1 therapy and meets criteria consistent with anti-PD-1 primary resistance (i.e., primary anti-PD-1 non-responder), or
  3. Has received prior anti-PD-1 therapy and meets criteria consistent with anti-PD-1 secondary resistance (i.e., secondary anti-PD-1 non-responder)

Expansion:

  1. Expansion Cohorts 1 and 3: Has received prior anti-PD-1 therapy and meets criteria consistent with anti-PD-1 primary or secondary resistance as described above
  2. Expansion Cohort 2: Has not received prior anti-PD-1 therapy (i.e., anti-PD-1 naïve)

    • 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 immune-related adverse events related to administration of anti-PD-1/L1 that led to the termination of the previous anti-PD-1 therapy due to intolerance or toxicity and precludes further PD-1 exposure
  • Symptomatic central nervous system metastases and/or carcinomatous meningitis
  • Active autoimmune disease that has required systemic treatment in the past 1 year
  • Known HIV or active hepatitis B/C infection
  • Active infection requiring intravenous treatment with antibiotics
  • 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 defined as more than 5 lesions overall including the primary tumor
  • Locoregional recurrent HNSCC with ulceration
  • Has received prior therapy with a checkpoint inhibitor, within 2 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 ClinicalTrials.gov identifier (NCT number): NCT03589339


Contacts
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Contact: Pavel Tyan, MD +49 176 81319375 pavel.tyan@nanobiotix.com
Contact: Rodney Carter +1 (617) 460-6609 rodney.carter@nanobiotix.com

Locations
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United States, Delaware
Christiana Care Health Services Recruiting
Newark, Delaware, United States, 19713
Contact: Jamal Misleh, 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, 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: Scott Herbert, 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
Nanobiotix
Investigators
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Study Director: Pavel Tyan, MD Nanobiotix
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Responsible Party: Nanobiotix
ClinicalTrials.gov Identifier: NCT03589339    
Other Study ID Numbers: 1100
First Posted: July 17, 2018    Key Record Dates
Last Update Posted: June 24, 2022
Last Verified: June 2022

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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
Neoplasms
Melanoma
Neoplasm Metastasis
Neoplasms, Second Primary
Breast Neoplasms
Squamous Cell Carcinoma of Head and Neck
Liver Neoplasms
Uterine Cervical Neoplasms
Urinary Bladder Neoplasms
Disease
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
Carcinoma, Squamous Cell
Neoplastic Processes
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urologic Diseases
Breast Diseases
Skin Diseases
Head and Neck Neoplasms
Genomic Instability