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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

20 Jan 2026 → ongoing

Decision date (initial)

2025-12-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To determine the rate of patients with a CCR with organ preservation of the face and oral cavity at two years of FU without compromising clinical outcome for all patients.

Secondary objectives 7

1. To determine the CCR rate (as defined in the primary endpoint) in Arm A at intermediate time-points.
2. To evaluate health-related QoL
3. To compare other time to event endpoints between Arm A and Arm B
4. Assessment of AEs and ir-AEs
5. To investigate cost-effectiveness
6. To measure oncological treatment duration and treatment stops;
7. Health care consumption / burden

Conditions and MedDRA coding

Head and Neck squamous cell carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 18 years of age or older
2. Primary advanced oral cavity squamous cell carcinoma (HNSCC) o Stage III-IVA according to TNM version 8.0 of the UICC/AJCC staging manual.
3. 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)
4. Indication for SOC*
5. No prior systemic oncological therapy
6. No prior radiotherapy to the head and neck
7. No immunosuppression
8. World Health Organisation (WHO) performance status of 0-2
9. 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.
10. 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.

Exclusion criteria 13

1. Inoperable OSCC (Stage IVB)
2. Distantly metastasized (Stage IVC) OSCC
3. Prior irradiation in the head and neck area.
4. Prior anti-PD(L)1 or anti-CTLA4 immune checkpoint-blockade.
5. 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.
6. Active human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
7. Positive test for hepatitis B virus surface antigen (HBsAg) or hepatitis C antibody (HCV Ab)
8. 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.
9. 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
10. 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)
11. Patients who are pregnant or breastfeeding
12. History of allergy to study drug components and/or history of severe hypersensitivity to any monoclonal antibody
13. Use of other investigational drugs 30 days before study drug administration and 5 half times before study inclusion

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. The percentage of patients in arm A with a CCR and organ preservation of the face and oral cavity at 24 months of FU*. Success is defined with a lower bound of the 95% CI >10%.
2. Non-inferiority of arm A compared to arm B in Recurrence Free Survival (RFS) after a minimum FU of 24 months since randomisation for each patient. An event is defined as disease progression to unresectable disease before surgery or before adjuvant (C)RT, OR recurrent disease after treatment, OR death due to any cause.

Secondary endpoints 7

1. The CCR rate in ARM A at 12 and 18 months
2. To assess the difference in Qol between Arm A and B on all domains of the EORTC QLQ H&N43 and the EORTC QLQ-C30, EQ-5D-5L, HADS. • And between the responders in Arm A vs Arm B. • And between the non-responders of Arm A vs Arm B. • And between responders and non-responders of arm A
3. Compare other survival endpoints between Arm A and B (Locoregional control (LRC), dis-tant metastasis free survival (DMFS), Disease specific survival (DSS), Recurrence Free Sur-vival (RFS), Event Free Survival (EFS) and Overall survival (OS)) at 12, 18 and 24 months FU
4. Compare AEs and ir-AEs in both arms using the CTCAE v5.0 and Clavien-Dindo up to 100 days after last treatment (immunotherapy, surgery or adjuvant (C)RT)
5. Cost-effectiveness of ARM A will be compared to ARM B in terms of incremental costs and quality adjusted life years
6. Treatment duration and stops of ARM A will be compared to ARM B.
7. Extent of surgery (type and hours), RT( days and total Gy), chemotherapy (typaeand cumulative dose), days of admission on the ward, visits, other interventions, etc. • Comparison between ARM A and B • Between the responders in Arm A vs Arm B. • And between the non-responders of Arm A vs Arm B. • And between responders and non-responders of arm A

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Sponsor organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Address

Plesmanlaan 121

City

Amsterdam

Postcode

1066 CX

Country

Netherlands

Scientific contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

Prof. dr. Lotje (C.L.) Zuur

Public contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

Prof. dr. Lotje (C.L.) Zuur

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 8 files

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

Application history

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