Clinical trial comparing induction treatment with EGFR-ADC MRG003 alone or in combination with the anti PD1 Pucotenlimab, followed by radiochemotherapy in locally advanced squamous cell cancers of the head and neck.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Groupe Oncologie Radiotherapie Tete Cou

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

13 Oct 2025 → ongoing

Decision date (initial)

2025-06-24

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, Efficacy, Safety

To compare the objective response rate (ORR) of patients with LA-HNSCC, treated with induction of EGFR-ADC MRG003 and anti-PD-1 Pucotenlimab versus EGFR-ADC alone before chemoradiotherapy.

Secondary objectives 6

1. To compare the complete response (CR) at 6 months after the end of chemoradiotherapy between two arms
2. To compare progression- free survival (PFS) between two arms.
3. To compare failure- free survival (FFS) between two arms.
4. To compare overall survival (OS) including OS rate at 24 and 36 months between two arms.
5. To evaluate and compare treatment compliance between arms
6. To evaluate adverse events graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and compare them between two arms

Conditions and MedDRA coding

locally advanced head and neck squamous cell carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Age ≥ 18 years, ≤ 75 years
2. Patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
3. Histologically confirmed diagnosis in previously untreated LA-SCCHN patients suitable for definitive CRT :  Stage III, IVA or IVB for oral cavity, hypopharynx, larynx or oropharynx (p16 negative) according to the American Joint Committee on Cancer [AJCC]/TNM Staging System, 8th Ed.) Or  Irrespective of tobacco consumption: T3-T4/N1-N3 p16 positive oropharyngeal squamous cell carcinoma (OPSCC) (p16 protein overexpression assessed by immunohistochemistry). Or  Only if tobacco consumption ≥ 20 pack - years: T1-T2/N1-N3 or T3-T4/N0 p16 positive OPSCC.
4. Evaluable tumor burden assessed by H&N-computed tomography scan (CT-scan) or magnetic resonance imaging (MRI), based on RECIST v 1.1
5. Patients eligible to cisplatin-based chemotherapy
6. No hearing loss by clinical assessment or ≤ grade 2 hearing impairment (according to NCI-CTCAE v.5).
7. Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to randomization: a. Polynuclear neutrophils >1.5 x 109/L b. Platelets > 100 x 109/L c. Hemoglobin > 9.0 g/dL d. ALAT/ASAT< 3.0 x ULN e. Total bilirubin < 1.5 x ULN (except Gilbert Syndrome: < 3.0 mg/dL) f. Glomerular filtration rate ≥ 50 mL/min/1.73m² (using the CKD-EPI creatinine formula [see Appendix 4])
8. No prior treatment with chemotherapy, immunotherapy and targeted therapy for H&N cancer, radiotherapy or surgery in the head and neck region.

Exclusion criteria 9

1. Metastatic disease (stage IVC as per AJCC/TNM, 8th Ed.).
2. Patients having received prior therapy with anti-PD1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
3. Treatment for other diseases with an investigational agent or use of an investigational device within 4 weeks of the first dose of study treatment.
4. History of another malignancy within the last 3 years prior to randomization, with the exception of completely resected non-melanoma cell skin cancer outside the head and neck area or completely resected stage I breast cancer, or completely resected in-situ non-muscular invasive bladder, cervix, uterine and/or prostate (Gleason 6) carcinomas, or T1a squamous cell carcinoma of the esophagus or rectum/anus.
5. Patients with clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication, or known persistent reduced left ventricular ejection fraction < 50%.
6. Other active infections (viral and/or bacterial and/or mycotic) requiring systemic treatment at the day before randomization
7. Documented weight loss of >10% during the last 4 weeks prior to randomization (unless adequate measures are undertaken for nutritional support).
8. Patients with positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
9. Patients with positive tests for hepatitis B virus surface antigen (HBsAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating active or chronic infection. Presence of other serious liver diseases, including chronic autoimmune hepatic disorders, primary biliary cirrhosis or sclerosing cholangitis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Best objective response rate evaluated by the investigators with head and neck radiological imaging according to RECIST version 1.1 criteria at the end of induction phase of EGFR-ADC MRG003 + anti-PD-1 Pucotenlimab or EGFR-ADC MRG003 alone (21 ± 7 days after the Day 1 of last cycle of induction treatment). Objective response (OR) includes complete and partial response

Secondary endpoints 5

1. • Progression-free survival (PFS) as the time from randomization to the first progression (locoregional/metastatic progression after induction, CRT or adjuvant treatment) or death from any cause, or the date of the last follow-up for patients who did not have progression or death.
2. • Failure-free survival (FFS) as the time from randomization to the first of the following events: locoregional /metastatic progression after the completion of CRT or failure to receive CRT; or death from any cause or the date of the last follow-up for patients who did not have these events.
3. • Overall survival (OS) defined as the time between randomization and death from any cause or date of the last follow-up for patients alive.
4. • Compliance: for radiotherapy, total tumor dose, total number of fractions, total duration and major deviations will be reported and for anti-PD-1 + EGFR-ADC and cisplatin, number of cycles/injection, total dose, total duration of the treatment and dose intensity, and relative dose intensity (i.e. ratio of the dose received by the planned total dose). Whatever the treatment, treatment interruption, reduction and discontinuation and their reasons will be reported.
5. • Incidence and severity of adverse events, serious adverse events and laboratory abnormalities as graded by the National Cancer Institute - Common Terminology Criteria of Adverse Events (NCI-CTCAE) v 5.0 from the randomization to one month after the end of the adjuvant treatment

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Groupe Oncologie Radiotherapie Tete Cou

Sponsor organisation

Groupe Oncologie Radiotherapie Tete Cou

Address

4 B Rue Emile Zola

City

Tours

Postcode

37000

Country

France

Scientific contact point

Organisation

Groupe Oncologie Radiotherapie Tete Cou

Contact name

Dr Yungan TAO

Public contact point

Organisation

Groupe Oncologie Radiotherapie Tete Cou

Contact name

Laura SINIGAGLIA

Locations

1 EU/EEA country · 19 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 9 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