JNJ-90301900 (NBTXR3) activated by radiotherapy with or without cetuximab in LA-HNSCC

ISRCTN	ISRCTN11941599
DOI	https://doi.org/10.1186/ISRCTN11941599
ClinicalTrials.gov (NCT)	NCT04892173
Clinical Trials Information System (CTIS)	2024-530386-31
Integrated Research Application System (IRAS)	1011758
Protocol serial number	NANORAY-312: Phase 3
Sponsor	Johnson And Johnson Enterprise Innovation Inc.
Funder	Johnson And Johnson Enterprise Innovation Inc.

Submission date: 15/05/2025
Registration date: 17/02/2026
Last edited: 17/02/2026

Recruitment status: Recruiting
Overall study status: Ongoing
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Ms Lynda McSorley
Public, Scientific, Principal investigator

50-100 Holmers Farm Way
High Wycombe
HP12 4DP
United Kingdom

Phone	+44 01494 658990 Ext 8990
Email	lmcsorle@its.jnj.com

Study information

Primary study design	Interventional
Allocation	Randomized controlled trial
Masking	Open (masking not used)
Control	Active
Assignment	Parallel
Purpose	Treatment
Scientific title	A Phase 3 Study of NBTXR3 Activated by Investigator's Choice of Radiotherapy Alone or Radiotherapy in Combination With Cetuximab for Platinum-based Chemotherapy-Ineligible Elderly Patients With LA-HNSCC
Study objectives	-
Ethics approval(s)	Approved 06/08/2025, East Midlands - Nottingham 2 Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 207 104 8065; nottingham2.rec@hra.nhs.uk), ref: 25/WM/0107
Health condition(s) or problem(s) studied	Locally advanced head & neck squamous cell carcinoma
Intervention	Participants will undergo a screening assessment over a period of less than or equal to (<=) 28 days to determine eligibility. Eligible participants will be treated by the Investigator's choice of RT alone or RT in combination with cetuximab. Following theInvestigator's choice, participants will be randomized in a 1:1 ratio: Arm A: JNJ-90301900 (NBTXR3), as an intratumoral/intranodal injection, activated by investigator's choice of RT alone or RT incombination with cetuximab Arm B: Investigator's choice of RT alone or RT in combination with cetuximab All participants (Arm A and Arm B) will receive 70 Gy in 35 fractions over a 7 week period. An EOT visit will be performed 4 weeks after the completion of RT. Follow-up visits will start at 12 weeks post-RT completion, and willcontinue every 12 weeks for 2 years, and then every 24 weeks thereafter until death; the participant is determined to be lost to follow up;withdrawal of consent; or the end of the study, whichever occurs first. Participants who have received further anti-cancer therapy for thestudy disease and/or have had disease progression/recurrence will be followed only for survival information Experimental: Arm A -JNJ-90301900 (NBTXR3), as an intratumoral/intranodal injection, activated by investigator's choice of RT alone or RT in combination with cetuximab. JNJ-90301900 (NBTXR3) is given as a dose of 33%of the Gross Tumor Volume. - Drug: JNJ-90301900 (NBTXR3) - Suspension of inert, crystalline hafnium oxide particles, designed to generate oxygen free radicals to destroy cancer cells after activation by ionizing radiation. - Other Names: -- Functionalized hafnium oxide nanoparticles -- NBTXR3 - Drug: Cetuximab - Solution for infusion - Other Names: -- Erbitux - Radiation: Radiation Therapy - Intensity-modulated radiation therapy (IMRT): 70Gray in 35 fractions over a 7-week period. Active Comparator: Arm B - Investigator's choice of RT alone or RT in combination with cetuximab. - Drug: Cetuximab - Solution for infusion - Other Names: -- Erbitux - Radiation: Radiation Therapy - Intensity-modulated radiation therapy (IMRT): 70Gray in 35 fractions over a 7-week period.
Intervention type	Drug
Phase	Phase III
Drug / device / biological / vaccine name(s)	Cetuximab, JNJ-90301900 [Hafnium Oxide]
Primary outcome measure(s)	Progression-free Survival (PFS).Time from randomization to local-regional recurrence, local-regional progression, distant progression, or death from any cause, whichever occurs first measured using patient records up to 30 months following first randomized participant
Key secondary outcome measure(s)	1. Overall Survival (OS). Time from randomization to death from any cause measured using patient records up to 48 months following first randomized participant 2. Local-regional control. Time to local regional progression: time from Randomization to local-regional progression or death, whichever occurs first measured using patient records up to 48 months following first randomized participant 3. Distant control. Time to distant progression: time from Randomization to distant progression or death, whichever occurs first measured using patient records up to 48 months following first randomized participant 4. Objective Response Rate (ORR). Rate of complete response (CR)+partial response (PR) [RESIST 1.1] measured using patient records up to 48 months following first randomized participant 5. Duration of Overall Response. Time from CR or PR to progression of disease, unequivocal clinical progression, or death, whichever occurs first measured using patient records up to 48 months following first randomized participant 6. Quality of Life over time - QLQ H&N35. Change from baseline over time in symptoms, function, and health related QOL using the European Organisation for Research and Treatment of Cancer (EORTC) questionnaire-Head and Neck Cancer Module (QLQ H&N35) up to 48 months following first randomized participant 7. Quality of Life over time - EQ 5D 5L. Change from baseline over time in symptoms, function, and health related QOL using the 5 level EuroQol 5 dimension (EQ 5D5L) instrument up to 48 months following first randomized participant 8. Safety across duration of study. Adverse events (AEs) measured using patient records up to 48 months following first randomized participant
Completion date	31/12/2028

Eligibility

Participant type(s)
Age group	Mixed
Lower age limit	60 Years
Upper age limit	120 Years
Sex	All
Target sample size at registration	500
Key inclusion criteria	1. Age greater than or equal to (>=) 60 years old 2. Squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or supraglottic larynx and a candidate for definitive radiation therapy with or without cetuximab 3. Clinical stage T3-4 NX or T2 N2-3 disease according to the 8th edition of AJCC 4. One primary tumor lesion amendable for intratumoral injection 5. Ineligible to receive platinum-based chemotherapy with radiation (at least one of the following): - Estimated creatinine clearance >= 30 and less than (<) 50 milliliters/minute (mL/min) (per Cockcroft-Gault equation),Grade >= 2 hearing loss or tinnitus, Grade >= 2 peripheral neuropathy, Eastern Cooperative Oncology Group (ECOG)Performance Status 2 or New York Heart Association Class 3 - Age 70-74 years old with Geriatric 8 (G8) score less than or equal to (<=) 14 - Age >= 75 years old
Key exclusion criteria	1. Carcinoma of the nasopharynx, paranasal sinus(es), salivary gland, thyroid gland, or unknown primary 2. Non-squamous cell histology 3. Clinical stage T1-2 N0, T2 N1, or M1 disease according to the 8th edition of AJCC 4. Loco-regionally recurrent head & neck cancer that has been previously treated with surgery, radiation therapy, and/or chemotherapy 5. Prior or concurrent primary malignancy (including second synchronous head & neck cancer) within the last 2 years of informed consent and whose natural history has the potential to interfere with the safety and efficacy assessment of the investigational agent 6. Ongoing or active infection requiring treatment with antimicrobial therapy within 2 weeks of randomization
Date of first enrolment	05/01/2022
Date of final enrolment	31/05/2027

Locations

Countries of recruitment

United Kingdom
Austria
Belgium
Brazil
Bulgaria
Canada
China
Croatia
Czech Republic
Finland
France
Georgia
Germany
Greece
Hungary
India
Israel
Japan
Korea, South
Philippines
Portugal
Romania
Serbia
Spain
Sweden
Taiwan
United States of America

Study participating centre

-
-
-
England

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The data sharing policy of the Janssen Pharmaceutical Companies of Johnson and Johnson is available at www.janssen.com/clinical- trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Editorial Notes

15/05/2025: Study's existence confirmed by Health Research Authority (HRA) (UK)