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NBTXR3 treatment activated by radiotherapy for advanced cancer patients receiving 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

Phase 1 Interventional Nanobiotix · NCT03589339

This study is testing a new treatment called NBTXR3, which is activated by radiation, to see if it can help advanced cancer patients who are also receiving anti-PD-1 therapy feel better and improve their outcomes.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment145 (estimated)
Ages18 Years and up
SexAll
SponsorNanobiotix Industry-sponsored
Drugs / interventionsradiation, immunotherapy
Locations13 sites (San Francisco, California and 12 other locations)
Trial IDNCT03589339 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of NBTXR3, a novel treatment activated by radiotherapy, in combination with anti-PD-1 therapy for patients with advanced cancers. The study includes a dose escalation and expansion approach, targeting patients with various types of cancers, including head and neck squamous cell carcinoma and metastases to the lungs or liver. Participants will receive an intratumoral injection of NBTXR3, with the aim of enhancing the effects of radiotherapy and improving overall treatment outcomes. The trial is designed to assess both the local and systemic effects of the treatment.

Who should consider this trial

Good fit: Ideal candidates include patients with advanced cancers such as head and neck squamous cell carcinoma or those with lung or liver metastases who are eligible for anti-PD-1 therapy.

Not a fit: Patients with cancers that are operable or those who do not qualify for anti-PD-1 therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve outcomes for patients with advanced cancers who have limited treatment options.

How similar studies have performed: While this approach is innovative, similar studies have shown promise in enhancing the efficacy of immunotherapy with localized treatments.

Eligibility criteria

Show full inclusion / exclusion 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

Where this trial is running

San Francisco, California and 12 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions RadiotherapyImmunotherapyMicrosatellite Instability-High Solid Malignant TumourMetastasis from Malignant Tumor of LiverSquamous Cell Carcinoma of Head and NeckMetastasis from Malignant Tumor of CervixMetastatic Renal Cell CarcinomaMetastasis from Malignant Melanoma of Skin
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.