IMCISION: Towards organ preservation and cure via ultra-short immunotherapy in advanced oral cancer. The IMCISION II trial, an investigator-initiated multicentre randomised phase 3 trial

Prior treatment

• Prior systemic oncological therapy for the current primary tumour
• Prior radiotherapy for the current primary tumour
• Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids (up to 10 mg of prednisone per day is allowed)
• Use of other investigational drugs 30 days before study drug administration and 5 half times before study inclusion
• Prior anti-PD(L)1 or anti-CTLA4 immune checkpoint-blockade.
• Prior diagnosed malignancies, except malignancies with a 2 year survival rate of over >90% (eg. certain skin cancers, low-grade prostate carcinoma) and where treatment does not interfere with the treatment of patients included in this trial.

Other illness

• Positive test for hepatitis B virus surface antigen (HBsAg) or hepatitis C antibody (HCV Ab)
• Subjects with any active autoimmune disease or a documented history of autoimmune disease, except: o Subjects with vitiligo o Resolved childhood asthma/atopy o Residual hypothyroidism due to an autoimmune condition requiring only hormone replacement o Psoriasis without the need for systemic treatment o Any condition not expected to recur in the absence of an external trigger.
• Underlying medical conditions that, in the investigator's opinion, will make the administration of the study drug hazardous or obscure the interpretation of toxicity or AEs
• History of allergy to study drug components and/or history of severe hypersensitivity to any monoclonal antibody
• Active human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)

Other

• Inoperable OSCC (Stage IVB)
• Patients who are pregnant or breastfeeding
• Distantly metastasized (Stage IVC) OSCC

• 18 years of age or older
•  No prior radiotherapy for the current primary tumour
• Prior surgery for the current primary tumour is allowed
• Patients willing and able to understand the Dutch study information and protocol requirements and comply with the treatment/intervention schedule, scheduled visits, and other requirements of the study.
• Primary advanced oral cavity squamous cell carcinoma (HNSCC) o Stage III-IVA according to TNM version 9.0 of the UICC/AJCC staging manual.
• Primary tumour site: o Malignant neoplasm of other and unspecified parts of tongue (C02.0-C02.3, C02.8-9) o Malignant neoplasm of gum (C03) o Malignant neoplasm of floor of mouth (C04) o Malignant neoplasm of hard palate (C05.0, C05.8-9) o Malignant neoplasm of other and unspecified parts of mouth (C06)
• Indication for SOC*
• No prior systemic oncological therapy for the current primary tumour
• No immunosuppression
• World Health Organisation (WHO) performance status of 0-2
• Screening laboratory values must meet the following criteria: o WBC ≥ 2.0x109 /L o Neutrophils ≥1.5x109 /L o Platelets ≥100 x109 /L o Hemoglobin ≥5.5 mmol/L o Creatinine ≤1.5x upper limit of normal (ULN) o AST ≤ 1.5 x ULN o ALT ≤ 1.5 x ULN o Bilirubin ≤1.5 X ULN (except patients with Gilbert Syndrome, who are eligible when total bilirubin < 3.0 mg/dL) o Women of child-bearing potential (WOCBP) must use appropriate method(s) of con-traception. They should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required time for nivolumab to undergo five x T1/2, ipilimumab has a much shorter T1/2) after the last dose of the IMP. o WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25IU/L or equivalent units of HCG) prior to the start of ICB.