NOCANO: Nivolumab as neoadjuvant immunotherapy for patients with Oral CANcer and identification of response-predictive biomarkers in tumour draining lymph NOdes

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Karolinska University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-05-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the efficacy of two doses neoadjuvant nivolumab in reducing primary tumour size at the time of surgery.

Secondary objectives 5

1. To evaluate safety, tolerability and toxicity of two doses nivolumab prior surgery
2. To evaluate progression-free survival (PFS), event-free survival (EFS) and overall survival (OS)
3. To evaluate the effect of neoadjuvant nivolumab treatment on a quality of life (QOL)
4. To determine HPV status in tumour
5. To evaluate effects of neoadjuvant nivolumab treatment on metastatic lymph nodes

Conditions and MedDRA coding

Oral squamous cell carcinoma (OSCC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. The subject is willing to participate and has given their written and dated consent to participate in the trial.
2. Naïve to immunotherapy.
3. ≥ 18 years of age* at the time of signing the informed consent.
4. Primary histologically or cytologically confirmed OSCC classified according to the ICD-10 classification: C02.0, C02.1, C02.2, C02.3, C02.8 C02.9, C03.0, C03.1, C03.9, C04.0, C04.1, C04.8, C04.9, C06.0, C00.3, C00.4, C05.0, C06.1, C06.2, C06.8, C06.9.
5. Stage T2-4 N0-3 M0 according to the UICC TNM classification of Malignant Tumours.
6. The subject is planned for curative surgery as the primary treatment.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion criteria 29

1. Distant metastases (pathologically proven, radiologic or clinical evidence of distant metastatic disease). This includes all diseases below the clavicles, as well as disease metastatic to the bone, brain, or in the spinal canal.
2. Active malignancy requiring concurrent treatment or history of another primary malignancy.
3. History of radio- and/or chemotherapy.
4. Pregnant, breastfeeding, planning pregnancy or refusal to use highly effective contraception method during the treatment period and for at least 5 months after the last dose.
5. History of systemic treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
6. Prior organ transplantation.
7. Treatment with a live (attenuated) vaccine within 4 weeks before Screening visit.
8. Initiation of allergen immunotherapy within 3 months prior Screening visit or a plan to begin therapy during the trial.
9. Known or suspected systemic hypersensitivity to the active substance nivolumab including any of the OPDIVO™ excipients.
10. History of systemic hypersensitivity or anaphylaxis to other monoclonal antibodies including any excipient.
11. Active, known, or suspected autoimmune disease or inflammatory disease (e.g. lupus, inflammatory bowel disease [e.g. colitis or Crohn’s disease]), diverticulitis, rheumatoid arthritis, Sarcoidosis, Wegener syndrome, Grave’s disease, uveitis, etc.) that has required systemic treatment with immune modifying agents in the last 2 years (e.g. replacement therapy such as thyroxine, insulin or physiological corticosteroids is not an exclusion criteria).
12. Presence of condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisolone equivalents) or other immunosuppressive medication within 14 days before the start of nivolumab therapy.
13. Severe asthma exacerbation requiring the admission to hospital with systemic CS within 4 weeks before Screening visit.
14. Known significant respiratory disease, including, but not limited to, pneumonitis, interstitial lung disease (ILD), COPD, cystic fibrosis.
15. Prior history or evidence of active ILD or non-infectious pneumonitis that required steroids.
16. Known or suspected condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome.
17. Recent history of myocardial infarction, cardiac arrhythmia, unstable angina pectoris, transient ischemic attack, or a known history of a hypercoagulable disease.
18. Known hepatitis B virus (HBV) and/or hepatitis C virus (HCV) acute or chronic infection. If suspected, tests for hepatitis B surface antigen (HBs Ag) and/or HCV antibody (HCV Ab) confirmed by HCV ribonucleic acid (RNA) are required.
19. Known human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS) or positive HIV 1/2 serology test result if suspected.
20. Active tuberculosis (TB), non-tuberculous mycobacterial infection, a history of incompletely treated TB. TB test if suspected.
21. Known or suspected immunodeficiency, including history of invasive opportunistic infections (e.g. TB, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis or aspergillosis) despite infection resolution, or otherwise recurrent infections of abnormal frequency or prolonged duration suggesting a compromised immune system status, as judged by the Investigator.
22. Uncontrolled concurrent medical disorder affecting organ function and in the opinion of the Investigator may increase the risk for the subject or may interfere with the treatment and thus affect the study results or assessment.
23. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
24. Known or suspected heavy drinking and/or drug use.
25. In the opinion of the Investigator, the subject is unfit or unsuitable to receive neoadjuvant nivolumab, whatever the reason, including medical or clinical condition.
26. Any mental inability (e.g. dementia), reluctance or language difficulties that result in difficulty understanding the meaning of participation in the clinical trial and following the study protocol and instructions.
27. Lack of adherence to the study protocol and instructions given by the Investigator.
28. Premature withdrawal by the Investigator/Sponsor due to safety or any other reason.
29. Revoked consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Frequency of response measured as Objective Response Rate (ORR) based on the standard RECIST v1.1
2. Frequency of pathological response measured as pCR (no residual tumour cells in tumor bed or lymph nodes), MPR (≤10% residual viable tumour), pPR (≤50% residual viable tumour)
3. Frequency of volumetric (clinical/radiographic) tumour response

Secondary endpoints 19

1. Incidence of treatment-related Adverse events (TRAEs)
2. Incidence of Serious adverse events (SAE)
3. Change from baseline in laboratory parameters (including hematologic and biochemical parameters)
4. Change from baseline in vital signs (including heart rate, systolic and diastolic blood pressure, body temperature, respiratory rate)
5. Change from baseline in ECG values
6. Incidence of surgery delays or surgery cancelation due to disease progression or TRAEs during the neoadjuvant treatment period
7. Rate of postoperative complications
8. Incidence of reduced extent of surgical intervention with achieved negative/clear surgical margins (SM) or spared from surgery due to complete response to neoadjuvant therapy
9. Incidence of immunogenicity as measured by the presence of antidrug antibody (ADA) and neutralizing antibodies (NAb) to nivolumab
10. Proportion of participants with PFS and EFS at distinct timepoints up to 5-year follow-up
11. Rate of overall survival at distinct timepoints up to 5-year follow-up
12. Time to the first event (progression, recurrence or death) and frequency
13. Change from baseline at distinct timepoints measured by EORTC QLQ-C30 and EORTC QLQ-H&N35
14. Time to clinically meaningful improvement or deterioration
15. Change in questionnaire completion rates over time
16. Incidence of HPV
17. Correlation of HPV status and response to neoadjuvant therapy as defined RECIST 1.1
18. Proportion of patients with response at lymph nodes
19. Change in the number of metastatic lymph nodes

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karolinska University Hospital

Sponsor organisation

Karolinska University Hospital

Address

Eugeniavagen 3

City

Solna

Postcode

171 64

Country

Sweden

Scientific contact point

Organisation

Karolinska University Hospital

Contact name

Lars Olaf Cardell

Public contact point

Organisation

Karolinska University Hospital

Contact name

Lars Olaf Cardell

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications