Evaluation of the Efficacy and Safety of Nivolumab Neoadjuvant Treatment of Patients With Locally Advanced Oral Squamous Cell Carcinoma (NOCANO)

NOCANO: Nivolumab as Neoadjuvant Immunotherapy for Patients With Oral CANcer and Identification of Response-predictive Biomarkers in Tumour Draining Lymph NOdes

This is a Phase II, single-centre, non-randomized, single-arm clinical trial to investigate the efficacy and safety of neoadjuvant nivolumab therapy in adult participants with resectable, locoregionally advanced Oral Squamous Cell Carcinoma (OSCC) tumors. Identification of predictive molecular biomarkers of tumor response to treatment will also be performed.

Study Overview

• Status: Not yet recruiting
• Conditions: Oral Squamous Cell Carcinoma (OSCC)
• Intervention / Treatment: Drug: Nivolumab (240 mg)

Detailed Description

Patients 18 years old and above, any gender, naïve to immunotherapy, and with histologically confirmed T2-4 N0-3 M0 resectable Oral Squamous Cell Carcinoma tumors will be eligible for this clinical trial. Enrolled patients must be fit and eligible for the primary treatment of curative surgery at the primary tumor site with sentinel node identification and removal. Total 60 patients fulfilling eligibility criteria will be included during the period of three years and will receive a total of 2 doses (240 mg per dose) of nivolumab at day 1 and day 15 prior to the curative standard of care surgery. After the study treatment and standard of care surgery, the study participants will be offered evidence-based adjuvant therapy, such as radiotherapy, chemoradiotherapy and checkpoint inhibitors or combination treatments, according to the existing evidence.

The study duration per participant after inclusion is approximately 27 weeks including two study-related follow-up visits at 3 and 6 months after the second nivolumab dose. Survival status and disease status of every participant will be also reviewed in medical records at 1, 2, 3 and 5 years after the second nivolumab dose.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lars Olaf Cardell, MD, PhD; Phone Number: +468-123 70 000; Email: lars-olaf.cardell@regionstockholm.se
• Study Contact Backup: Name: Hanna Carstens, MD; Email: hanna.carstens@regionstockholm.se

Study Locations

• Sweden
  • Stockholm, Sweden
    • Karolinska University Hospital, Head-, neck-, lung- and skin cancer, Theme Cancer
    • Principal Investigator: Hanna Dr Carstens

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The subject is willing to participate and has given their written and dated consent to participate in the trial.

• Naïve to immunotherapy.

  ≥ 18 years of age at the time of signing the informed consent.

• Primary histologically or cytologically confirmed Oral Squamous Cell Carcinoma classified according to the ICD-10 classification.
• Stage T2-4 N0-3 M0.
• The subject is planned for curative surgery as the primary treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

• 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.
• Active malignancy requiring concurrent treatment or history of another primary malignancy.
• History of radio- and/or chemotherapy.
• 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.
• 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.
• Prior organ transplantation.
• Treatment with a live (attenuated) vaccine within 4 weeks before Screening visit.
• Initiation of allergen immunotherapy within 3 months prior Screening visit or a plan to begin therapy during the trial.
• Known or suspected systemic hypersensitivity to the active substance nivolumab including any of the OPDIVO™ excipients.
• History of systemic hypersensitivity or anaphylaxis to other monoclonal antibodies including any excipient.
• 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).*The subject may enroll if they have vitiligo, alopecia, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
• 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.
• Severe asthma exacerbation requiring the admission to hospital with systemic corticosteroids within 4 weeks before Screening visit.
• Known significant respiratory disease, including, but not limited to, pneumonitis, interstitial lung disease (ILD), chronic obstructive pulmonary disease, cystic fibrosis.
• Prior history or evidence of active ILD or non-infectious pneumonitis that required steroids
• Known or suspected condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome.
• Recent history of myocardial infarction, cardiac arrhythmia, unstable angina pectoris, transient ischemic attack, or a known history of a hypercoagulable disease.
• 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.
• Known human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS) or positive HIV 1/2 serology test result if suspected.
• Active tuberculosis (TB), non-tuberculous mycobacterial infection, a history of incompletely treated TB. TB test if suspected.
• 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.
• 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.
• 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.
• Known or suspected heavy drinking and/or drug use.
• In the opinion of the Investigator, the subject is unfit or unsuitable to receive neoadjuvant nivolumab, whatever the reason, including medical or clinical condition.
• 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.
• Lack of adherence to the study protocol and instructions given by the Investigator.
• Premature withdrawal by the Investigator/Sponsor due to safety or any other reason.
• Revoked consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant treatment; Drug:Nivolumab	Drug: Nivolumab (240 mg); Nivolumab at day 1 and day 15 prior to the curative standard of care surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of response	Frequency of tumor response measured as Objective Response Rate (ORR) based on the standard RECIST v1.1 criteria, assessed using radiographic images.	From start of neoadjuvant treatment to end of neoadjuvant treatment (before surgery), up to approximately 4 weeks
Frequency of pathological response	Tumour pathological response, defined as percentage residual tumour cells after treatment, measured as Pathologic Complete Response, pCR (no residual tumour cells in tumor bed or lymph nodes), Major Pathological Response, MPR (≤10% residual viable tumour), Pathological Partial Response, pPR (≤50% residual viable tumour).	From start of neoadjuvant treatment to end of neoadjuvant treatment (before surgery), up to approximately 4 weeks
Frequency of volumetric tumour response	Volumetric tumour response, measured by radiographic images and/or physical measurements and assessments.	From start of neoadjuvant treatment to end of neoadjuvant treatment (before surgery), up to approximately 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-related Adverse events (TRAEs)	Incidence of treatment related adverse events classified according to the definitions in NCI CTCAE version 5.0.	From start of neoadjuvant treatment up to and including 6 months.
Incidence of Serious adverse events (SAE)	Incidence of serious adverse events	From start of neoadjuvant treatment up to and including 6 months.
Change from baseline in hematology parameters	Change from baseline in white blood cells (WBC), white blood cell differentiation, absolute neutrophil count (ANC), thrombocytes/platelets, erythrocytes (haematocrit), (B)Erc-MCH, (B)Erc-MCV, haemoglobin (Hb).	From screening visit, assessed at regular intervals up to 6 months after first neoadjuvant treatment
Change from baseline in clinical chemistry parameters	Change from baseline in Electrolyte status: sodium (Na), potassium (K), calcium (Ca), creatinine, Liver status: albumin, bilirubin, alkaline phosphatase (ALP), alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), lactate dehydrogenase (LD), gamma-glutamyl transferase (GGT), Amylase, glucose, and c-reactive protein (CRP).	From screening visit, assessed at regular intervals up to 6 months after first neoadjuvant treatment
Change from baseline in vital signs	Change in vital signs including heart rate, systolic and diastolic blood pressure, body temperature, respiratory rate.	From screening visit up to 6 months after first neoadjuvant treatment
Change from baseline in Electrocardiogram (ECG) values	Change from baseline in ECG values, including ECG QT interval, heart rhythm and rate, ST segment and T wave	From screening visit up to 6 months after first neoadjuvant treatment
Rate of postoperative complications	Rate of postoperative complications	From surgery to date of any postoperative complication, assessed up to 5 months post surgery
Incidence of surgery delays or surgery cancelation	Incidence of surgery delays/cancellations due to disease progression or treatment related adverse reactions during the neoadjuvant treatment period.	From start of neoadjuvant treatment to date of surgery, assessed up to 6 months
Incidence of reduced extent of surgical intervention	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.	At surgery, 3 weeks after start of neoadjuvant treatment
Incidence of immunogenicity	Incidence of immunogenicity as measured by the presence of antidrug antibody (ADA) and neutralizing antibodies (NAb) to nivolumab	From pre-screening to 5 months after surgery
Proportion of participants with progression-free survival (PFS) and event-free survival (EFS) at distinct timepoints	Number of patients that had not experienced disease progression (PFS) or any event (EFS) such as recurrence, treatment-related complications, or death at distinct time points.	From second dose of neoadjuvant treatment, assessed one, two, three, four and five years after the second dose of neoadjuvant treatment
Rate of overall survival at distinct timepoints up to 5-year follow-up	Number of patients that survived at distinct time points up to 5-year follow-up	From second dose of neoadjuvant treatment, assessed one, two, three, four and five years after second dose of neoadjuvant treatment.
Effect of neoadjuvant nivolumab treatment on a quality of life (QOL)	Time to clinically relevant changes defined as ≥10-point change for all scales in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck 35 (EORTC QLQ-H&N35).	From screening visit assessed up to 6 months
Incidence of HPV status in tumour	HPV status assessment of tumor and incidence reporting during pre-screening.	At pre-screening visit, 1-5 weeks before first neoadjuvant treatment
Correlation of HPV status and response to neoadjuvant therapy	Correlation of HPV status and response to neoadjuvant therapy as defined RECIST 1.1	From pre-screening visit to end of neoadjuvant treatment, up to 8 weeks
Proportion of patients with response at lymph nodes	Lymph node response, according to the RECIST v1.1 criteria	From pre-screening to surgery, up to 8 weeks
Change in the number of metastatic lymph nodes	Number of metastatic lymph nodes, defined according to the RECIST v1.1 criteria.	From prescreening to surgery, up to 8 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation and evaluation of various biomarkers to nivolumab treatment response, prognosis and survival	Correlation of different biological markers, immune cell populations, gene expression and protein signatures, analyzed from sequential tumor and lymph node biopsies and blood, with treatment efficacy, prognosis and safety.	From pre-screening visit to last blood/tumour sample taken, until the date of first documented progression, assessed up to 5 years after the second neoadjuvant dose.

Collaborators and Investigators

• Sponsor: Prof. Lars Olaf Cardell

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2033

Study Registration Dates

• First Submitted: February 27, 2026
• First Submitted That Met QC Criteria: April 1, 2026
• First Posted (Actual): April 7, 2026

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: neoadjuvant; Nivolumab; anti-PD-1
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab
• Other Study ID Numbers: NOCANO_SWE; 2025-521006-18-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No