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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Renal Cell Carcinoma; Squamous Cell Carcinoma of Head and Neck; Radiotherapy; Immunotherapy; Microsatellite Instability-High Solid Malignant Tumour; Metastasis From Malignant Tumor of Liver; Metastasis From Malignant Tumor of Cervix; Metastasis From Malignant Melanoma of Skin (Disorder); Metastatic Triple-Negative Breast Carcinoma; Metastatic NSCLC; Metastasis From Malignant Tumor of Bladder (Disorder)
• Intervention / Treatment: Drug: NBTXR3; Radiation: SABR; Drug: Nivolumab; Drug: Pembrolizumab

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: Interventional
• Enrollment (Estimated): 145
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Pavel Tyan, MD; Phone Number: +49 176 81319375; Email: pavel.tyan@nanobiotix.com

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94158
      • Recruiting
      • University of California San Francisco
      • Contact: Jason Chan, MD
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
      • Contact: George Yang, MD
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Recruiting
      • Emory University
      • Contact: William Stokes, MD
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago Medical Center
      • Contact: Ari Rosenberg, MD
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Active, not recruiting
      • Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Karmanos Cancer Institute
      • Contact: Ammar Sukari, MD
    • Detroit, Michigan, United States, 48202
      • Active, not recruiting
      • Henry Ford Cancer Institute
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • Recruiting
      • Christus St. Vincent Regional Cancer Center
      • Contact: Andrea Teague, MD
  • New York
    • Manhasset, New York, United States, 11030
      • Recruiting
      • Northwell Health
      • Contact: Bhupesh Parashar, MD
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27516
      • Recruiting
      • University of North Carolina, School of Medicine
      • Contact: Colette Shen, MD, PhD
  • Ohio
    • Canton, Ohio, United States, 44718
      • Recruiting
      • Gabrail Cancer Center
      • Contact: Nashat Gabrail, MD
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • Recruiting
      • St Luke's University Health Network
      • Contact: William Smith, MD
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Recruiting
      • Sanford Cancer Center
      • Contact: Michele Lohr, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: Opdivo; Drug: Pembrolizumab; Anti-PD-1 monotherapy; Other Names: Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[Dose Escalation Part]: Determination of the Recommended Dose	Determination of DLTs, the MTD (if possible), and RP2Ds for each cohort	24 Months
[Dose Expansion Part]: Safety Evaluation at RP2D	Incidence of Grade 3 and higher treatment-related AEs	24 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the anti-tumor response of R3/RT/PD-1	Evaluation of the Objective Response Rate: complete or partial response, as defined by RECIST 1.1 and iRECIST	24 months
Assessment of the safety and feasibility of R3/RT/PD-1	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	24 months
Evaluation of the body kinetic profile of intratumorally injected NBTXR3	Evaluation of the time-course dependent accumulation of hafnium in blood and urine following NBTXR3 intratumoral injection	24 months

Collaborators and Investigators

• Sponsor: Nanobiotix
• Investigators: Study Director: Pavel Tyan, MD, Nanobiotix

Publications and helpful links

General Publications

• Shen C, Frakes J, Niu J, et al 684 NBTXR3 activated by radiotherapy in combination with nivolumab or pembrolizumab in patients with advanced cancers: results from an ongoing dose escalation phase I trial (Study 1100). Journal for ImmunoTherapy of Cancer 2022;10:doi: 10.1136/jitc-2022-SITC2022.0684

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2019
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): May 30, 2028

Study Registration Dates

• First Submitted: April 10, 2018
• First Submitted That Met QC Criteria: July 4, 2018
• First Posted (Actual): July 17, 2018

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Liver Metastasis; Oral Cavity Cancer; Oropharynx Cancer; Lung Metastasis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Skin Diseases; Neoplasms by Histologic Type; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Digestive System Neoplasms; Breast Diseases; Liver Diseases; Head and Neck Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplastic Processes; Neuroendocrine Tumors; Nevi and Melanomas; Carcinoma, Squamous Cell; Genomic Instability; Skin Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Neoplasms; Uterine Cervical Neoplasms; Breast Neoplasms; Carcinoma; Neoplasm Metastasis; Urinary Bladder Neoplasms; Melanoma; Squamous Cell Carcinoma of Head and Neck; Liver Neoplasms; Neoplasms, Second Primary; Microsatellite Instability; Melanoma, Cutaneous Malignant; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Pembrolizumab
• Other Study ID Numbers: 1100

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No