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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

Tracking Information
First Submitted Date  ICMJE April 10, 2018
First Posted Date  ICMJE July 17, 2018
Last Update Posted Date June 24, 2022
Actual Study Start Date  ICMJE January 16, 2019
Estimated Primary Completion Date March 30, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 16, 2020)
Determination of the Recommended Dose [ Time Frame: 24 Months ]
Determination of DLTs, the MTD (if possible), and RP2Ds for each cohort
Original Primary Outcome Measures  ICMJE
 (submitted: July 4, 2018)
  • Phase1: Determination of the Maximum Tolerated Doses and the early Dose Limitting Toxicities (DLT) [ Time Frame: 24 months ]
    To determine the Maximum Tolerated Dose/s and the early Dose Limiting Toxicities (DLT) of intratumoral/intralesional injection of NBTXR3 activated by SABR in combination with an anti-PD1 antibody,
  • Phase1: Determination of the Recommended Doses [ Time Frame: 24 months ]
    To determine the Recommended Dose/s of NBTXR3 given as intratumoral/Intralesional injection and activated by SABR in combination with an anti-PD1 antibody, in patients with: Locoregionally recurrent or metastatic HNSCC amenable to re-irradiation (RD1), Lung metastasis from HNSCC (not amenable to reirradiation if synchronous locoregional recurrence and metastasis) or NSCLC (not previously irradiated) (RD2), Liver metastasis from HNSCC (not amenable to reirradiation if synchronous locoregional recurrence and metastasis) or NSCLC (not previously irradiated) (RD3)
  • Phase2: Complete Response rate by RECIST version 1.1 [ Time Frame: 24 months ]
    To measure by RECIST v1.1 the Complete Response rate.
  • Phase2: Incidence of clinical and laboratory adverse events and serious adverse events [ Time Frame: 24 months ]
    To assess the incidence of clinical and laboratory adverse events and serious adverse events.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 19, 2020)
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: July 4, 2018)
  • Phase1: Incidence of clinical and laboratory adverse events and serious adverse events [ Time Frame: 24 months ]
    To assess the incidence of clinical and laboratory adverse events and serious adverse events.
  • Phase1: Late onset grade ≥ 3 NCI CTCAE adverse events [ Time Frame: 24 months ]
    To determine the late onset toxicity of NBTXR3 given as intratumoral/intralesional injection activated by SABR in combination with an anti-PD1 antibody. To assess the "late onset" grade ≥ 3 NCI CTCAE adverse events.
  • Phase2: Body Kinetic characterization by quantification of Hafnium in whole blood and urine. [ Time Frame: 24 months ]
    To characterize the body kinetic profile by quantification of Hafnium at day 1 of NBTXR3 intratumoral/intralesional injection, activated by SABR in combination with an anti-PD1 antibody.Whole blood will be collected at the end of injection up to 4 hours post end injection. Urine sample will be collected twice after injection.
  • Phase2: Tumor response assessment by RECIST version 1.1 and iRECIST criteria [ Time Frame: 24 months ]
    To assess tumor response by RECIST version 1.1 and iRECIST criteria
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE NBTXR3 Activated by Radiotherapy for Patients With Advanced Cancers Treated With An Anti-PD-1 Therapy
Official Title  ICMJE 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
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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)
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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
Interventions:
  • Drug: NBTXR3
  • Radiation: SABR
  • Drug: Nivolumab
  • Drug: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 21, 2022)
145
Original Estimated Enrollment  ICMJE
 (submitted: July 4, 2018)
125
Estimated Study Completion Date  ICMJE May 30, 2028
Estimated Primary Completion Date March 30, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pavel Tyan, MD +49 176 81319375 pavel.tyan@nanobiotix.com
Contact: Rodney Carter +1 (617) 460-6609 rodney.carter@nanobiotix.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03589339
Other Study ID Numbers  ICMJE 1100
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Nanobiotix
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Nanobiotix
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pavel Tyan, MD Nanobiotix
PRS Account Nanobiotix
Verification Date June 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP