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

NCT ID: NCT03589339

Last Updated: 2025-10-24

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 145 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-16
• Study Completion Date: 2027-08-30

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.

Conditions

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)

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

NBTXR3 activated by SABR followed by anti-PD-1 monotherapy

Intratumoral injection of NBTXR3 followed by SABR followed by monotherapy with nivolumab or pembrolizumab

Group Type: EXPERIMENTAL

NBTXR3

Intervention Type: DRUG

Single intra Tumoral injection

SABR

Intervention Type: RADIATION

Radiotherapy given as a definite number of fractions at the dose defined for each radiation field

Nivolumab

Intervention Type: DRUG

Anti-PD-1 monotherapy

Pembrolizumab

Intervention Type: DRUG

Anti-PD-1 monotherapy

Interventions

NBTXR3

Single intra Tumoral injection

Intervention Type: DRUG

SABR

Radiotherapy given as a definite number of fractions at the dose defined for each radiation field

Intervention Type: RADIATION

Nivolumab

Anti-PD-1 monotherapy

Intervention Type: DRUG

Pembrolizumab

Anti-PD-1 monotherapy

Intervention Type: DRUG

Other Intervention Names

Stereotaxic Ablative Radiotherapy; Stereotaxic Body Radiation Therapy; Opdivo; Keytruda

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nanobiotix

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pavel Tyan, MD

Role: STUDY_DIRECTOR

Nanobiotix

Locations

University of California San Francisco

San Francisco, California, United States

Moffitt Cancer Center

Tampa, Florida, United States

Emory University

Atlanta, Georgia, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Henry Ford Cancer Institute

Detroit, Michigan, United States

Christus St. Vincent Regional Cancer Center

Santa Fe, New Mexico, United States

Northwell Health

Manhasset, New York, United States

University of North Carolina, School of Medicine

Chapel Hill, North Carolina, United States

Gabrail Cancer Center

Canton, Ohio, United States

St Luke's University Health Network

Bethlehem, Pennsylvania, United States

Sanford Cancer Center

Sioux Falls, South Dakota, United States

Countries

United States

References

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

Reference Type: BACKGROUND

Other Identifiers

1100

Identifier Type: -

Identifier Source: org_study_id