ImmunotherApy for the Prevention of High-Risk Oral DIsorders malignanT transformation - APHRODITE trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Humanitas Mirasole S.p.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Otorhinolaryngologic Diseases [C09], Diseases [C] - Neoplasms [C04]

Trial duration

30 Jul 2025 → ongoing

Decision date (initial)

2025-07-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AIRC

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

The primary objective is to evaluate the activity of a short course of intralesional immunotherapy with mitazalimab on high risk OPMD (Oral Potentially Malignant Disorder)

Secondary objectives 2

1. • To evaluate the efficacy of study treatment on the risk of malignant transformation of OPMD • To evaluate the safety of study treatment • To assess the change of histological grade of OPMD • To evaluate impact on quality of life (QoL)
2. Exploratory objectives • To evaluate prognostic/predictive biomarkers through translational analysis of tissue and saliva sample • To describe alteration in endoscopic narrow banding imaging (NBI) in OPMDs assessment • To evaluate the impact of study treatment on OPMD LOH status

Conditions and MedDRA coding

Oral disorders

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Signed written informed consent
2. Male or female > 18 years of age
3. ECOG Performance status (PS) 0-2
4. Diagnosis of high risk OPMD (i.e. leucoplakia, erhytroplakia, erhytro-leukoplakia) as defined by any of the following criteria: a. OPMD with multifocal (≥2), or contiguous lesions of ≥ 3 cm, or a single lesion ≥ 4 cm or greater in largest diameter with at least 1 lesion with epithelial dysplasia (any degree) b. OPMD with 4-quadrant oral cavity involvement (any grade of dysplasia) c. OPMD in at least one lesion with moderate dysplasia (at least grade 2) d. OPMD with high risk dysplasia (G3) (WHO classification - Reibel at al. 2017)
5. OPMD with a minimal diameter of 2 cm
6. Be willing to provide tissue from newly obtained oral biopsies
7. Be willing to provide saliva samples for study purposes
8. Prior oral cavity squamous cell carcinoma will be allowed, provided there is an interval of at least 2 years since completion of their previous treatment.

Exclusion criteria 5

1. Previous immunotherapy (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, CD40 agonist, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint receptors);
2. Oral lesions due to histology confirmed Lichen Planus or GVHD (suspicious lichenoid lesions will be evaluated with the medical monitor);
3. Diagnosis of prior immunodeficiency or organ transplant requiring immunosuppressive therapy, or known HIV or acquired immunodeficiency syndrome (AIDS)-related illness
4. Vaccination within 4 weeks of the first dose of mitazalimab and while on trial is prohibited except for the administration of inactivated vaccines (for example, inactivated influenza vaccines);
5. Clinically significant cardiovascular disease, e.g. cardiac failure of New York Heart Association classes III-IV, uncontrolled coronary artery disease, cardiomyopathy, uncontrolled arrhythmia, uncontrolled; hypertension, or history of myocardial infarction in the last 12 months

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Best overall response rate (CR + PR rate) at 6 months, as defined by the percent change in clinical-pathologic composite score

Secondary endpoints 4

1. • Evaluate 3 years and overall malignant transformation rate • Measure drug-induced adverse events and any treatment interruption due to toxicities • Evaluate the change of histological grading of OPMD (based on the World Health Organization WHO classification)
2. • Assess patient reported outcomes, measured via PRO CTCAE at treatment start, at 6 months and then every three months for the following 18 months. Questionnaire will be derived by the NCI- PRO-CTCAE ITEMS-ITALIAN • To assess impact on patients’ quality of life, measured via EORTC QLQC30-HN43
3. Exploratory Endpoints • Correlate selected biomarkers in tissue and saliva with malignancy-free survival. • Assess narrow-band imaging (NBI) changes during the study treatment and follow up
4. • To evaluate the LOH status (to be considered positive in patients carrying OPMD with LOH at 3p14 and/or 9p21 plus at least at one additional chromosomal site (4q, 8p,11p,13q, or 17p) or in patients carrying OPMD with a prior oral cancer history and LOH at 3p14 and/or 9p21 (LOH defined according to EPOC trial) at baseline, at 6 months, and in case of malignant transformation.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Humanitas Mirasole S.p.A.

Sponsor organisation

Humanitas Mirasole S.p.A.

Address

Via Alessandro Manzoni 56

City

Rozzano

Postcode

20089

Country

Italy

Scientific contact point

Organisation

Humanitas Mirasole S.p.A.

Contact name

Paolo Bossi

Public contact point

Organisation

Humanitas Mirasole S.p.A.

Contact name

Paolo Bossi

Third parties 1

Locations

1 EU/EEA country · 5 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 13 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