NBTXR3, Radiation Therapy, and Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Cancer

NCT04862455 | Terminated Phase 2 DMC FDA Drug

• 2 other identifiers: 2020-0541NCI-2021-00122
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial investigates the effect of NBTXR3, radiation therapy, and pembrolizumab in treating patients with head and neck squamous cancer that has come back (recurrent) or has spread to other places in the body (metastatic). NBTXR3 may cause cell destruction when activated by radiation. Radiation therapy, such as stereotactic body radiation therapy, uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. And hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving NBTXR3, radiation therapy, and pembrolizumab may kill more tumor cells.

Conditions

Metastatic Head and Neck Squamous Cell Carcinoma; Recurrent Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (5)

• Progression free survival

  Will be estimated using the method of Kaplan-Meier. Median times and 95% the determination of best objective response.

  Time from NBTXR3 injection to local, regional or distant failure or death from any cause, whichever occurs first, assessed up to 2 years

• Local failure

  Will be defined as evidence of disease recurrence or progression by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and/or histologically confirmed within 2 cm of the radiation planning target volume (PTV).

  Up to 2 years

• Regional failure

  Will be defined as evidence of disease recurrence or progression by RECIST version 1.1 and/or histologically confirmed that is 2 cm or more outside the PTV and within the organ that received stereotactic body radiation therapy (SBRT).

  Up to 2 years

• Distant failure

  Will be defined as occurrence of new metastatic lesion(s) that were not identified at baseline (prior to NBTXR3 injection) or evidence of disease progression in metastatic sites identified at baseline that are outside of the organ receiving SBRT. Evidence of disease should be confirmed by RECIST version 1.1 and/or histologically.

  Up to 2 years

• Objective response rate

  Will be assessed per RECIST version 1.1, for the target and non-target lesion(s). Best response will be assessed as well.

  Up to 2 years

Secondary Outcomes (3)

• Duration of response

  Up to 2 years

• Overall survival

  Time from NBTXR3 injection to death from any cause, assessed up to 2 years

• Treatment related acute and late onset toxicities

  Up to 2 years

Study Arms (1)

Treatment (NBTXR3, RT, pembrolizumab)

EXPERIMENTAL

Patients receive hafnium oxide-containing nanoparticles NBTXR3 via injection intratumorally or intranodally on day 1. Beginning as early as day 3 and within 8 days of NBTXR3 injection, patients undergo SBRT QOD or hypofractionated RT QD over 1-2 weeks at the discretion of the treating radiation oncologist. Starting on the same day as radiation therapy, patients also receive pembrolizumab IV over 30 minutes every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.

Other: Hafnium Oxide-containing Nanoparticles NBTXR3; Radiation: Hypofractionated Radiation Therapy; Biological: Pembrolizumab; Radiation: Stereotactic Body Radiation Therapy

Interventions

Hafnium Oxide-containing Nanoparticles NBTXR3 OTHER

Given intratumorally/intranodally

Also known as: NBTXR3

Treatment (NBTXR3, RT, pembrolizumab)

Hypofractionated Radiation Therapy RADIATION

Undergo hypofractionated RT

Also known as: Hypofractionated Radiotherapy, hypofractionation, Radiation, Hypofractionated

Treatment (NBTXR3, RT, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (NBTXR3, RT, pembrolizumab)

Stereotactic Body Radiation Therapy RADIATION

Undergo SBRT

Also known as: SABR, SBRT, Stereotactic Ablative Body Radiation Therapy

Treatment (NBTXR3, RT, pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with biopsy proven R/M HNSCC that is considered incurable by local therapies.
• Participant must have at least 2 lesions
• At least one lesion will be the target lesion, which will be injected with NBTXR3 and radiated and must be in either the head and neck (HN) or lung or liver.
• The other lesion will be a non-target lesion, which will not be treated with NBTXR3 or RT, but will be followed for response.
• Prior systemic therapy (i.e., chemotherapy or targeted therapy) given as part of multimodal treatment for locally advanced disease is allowed.
• Prior anti-PD-1/L1 therapy allowed in the PD-1 refractory cohort (cohort 2)
• Have results from testing of human papillomavirus (HPV) status for oropharyngeal cancer defined as p16 immunohistochemistry (IHC) testing using CINtec p16 Histology assay, or equivalent, and a 70% cutoff point.
• If HPV status previously tested using aforementioned method or an equivalent, no additional testing needed.
• Oral cavity, hypopharynx, and larynx cancer are not required to undergo HPV testing by p16 IHC as by convention these tumor locations are assumed to be HPV negative
• Have provided tissue for PD-L1 biomarker analysis from a core or excisional biopsy, fine needle aspirate (FNA) not adequate.
• A newly obtained biopsy (within 90 days prior to NBTXR3 injection is preferred), but an archival sample is acceptable.
• PD-1/L1 naive patients with 1% =\< combined positive score (CPS) \< 20 based on IHC testing.
• PD-1/L1 refractory patients all CPS levels allowed
• Amenable to undergo the image guided intratumoral/intranodal injection of NBTXR3 in up to 3 target lesions, as per investigator or treating physician discretion.
• For the HN target lesions (\< 60 cm\^3 per site, total volume \< 120 cm\^3) may be injected and irradiated, including the primary tumor and involved lymph node(s).

You may not qualify if:

• Diagnosis other than HNSCC R/M with disease that is suitable for local therapy administered with curative intent
• Less than 6-month time interval from prior radiation to the HN given as part of multimodal treatment for locally advanced disease
• Prior radiation to the lung or liver target lesions
• History of severe immune-related adverse events observed with previous immunotherapy (anti-PD-1/L1) or known sensitivity (grade \>= 3) to any excipients
• Has received any approved or investigational anti-neoplastic agent or immunotherapy within 4 weeks prior to NBTXR3 injection.
• Except anti-PD-1 therapy for patients assigned to cohort 2 (PD-1/L1 refractory), which will not require a washout window.
• A reduced washout window may be considered for therapies with short half-lives (i.e., kinase inhibitors) after discussion with Nanobiotix and investigator
• Has not recovered from adverse events (AEs) due to previous anti-neoplastic or immune-oncology therapy and/or interventions (including radiation) to =\< grade 1.
• Participants with alopecia and =\< grade 2 neuropathy may be eligible
• Symptomatic central nervous system metastases and/or carcinomatous meningitis
• Participants with previously treated brain metastases may participate provided that those lesions are radiologically stable (i.e., without evidence of progression for at least 4 weeks by repeat imaging at screening), clinically stable, and without requirement of steroid treatment for at least 14 days prior to NBTXR3 injection
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).
• Replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid replacement \[=\< 10 mg prednisone\] therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• At screening, past medical history of:
• Drug related pneumonitis

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Radiation Dose Hypofractionation; Radiation; pembrolizumab; Radiosurgery

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics; Physical Phenomena; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Jay Reddy

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2021
• First Posted: April 28, 2021
• Study Start: April 7, 2021
• Primary Completion: January 21, 2026
• Study Completion: January 21, 2026
• Last Updated: January 23, 2026

Record last verified: 2026-01

Locations

US (1)