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

Inclusion Criteria:

• Patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

• Evaluable tumor burden assessed by H&N-computed tomography scan (CT-scan) ormagnetic resonance imaging (MRI), based on RECIST v 1.1

• Patients eligible to cisplatin-based chemotherapy

• No hearing loss by clinical assessment or ≤ grade 2 hearing impairment (according toNCICTCAE v.5

• No prior treatment with chemotherapy, immunotherapy and targeted therapy for H&Ncancer, radiotherapy or surgery in the head and neck region.

Exclusion Criteria:

• Metastatic disease (stage IVC as per AJCC/TNM, 8th Ed.).

• 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 targetingTcell co-stimulation or checkpoint pathways).

• Treatment for other diseases with an investigational agent or use of aninvestigational device within 4 weeks of the first dose of study treatment

• History of another malignancy within the last 3 years prior to randomization, withthe exception of completely resected non-melanoma cell skin cancer outside the headand neck area or completely resected stage I breast cancer, or completely resectedin-situ nonmuscular invasive bladder, cervix, uterine and/or prostate (Gleason 6)carcinomas, or T1a squamous cell carcinoma of the esophagus or rectum/anus.

• Patients with clinically significant (i.e., active) cardiovascular disease: cerebralvascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New YorkHeart Association Classification Class II), or serious cardiac arrhythmia requiringmedication, or known persistent reduced left ventricular ejection fraction < 50%.

• Patients with positive test for human immunodeficiency virus (HIV) or known acquiredimmunodeficiency syndrome (AIDS).

• Patients with positive tests for hepatitis B virus surface antigen (HBsAg) orhepatitis C virus ribonucleic acid (HCV RNA) indicating active or chronic infection.Presence of other serious liver diseases, including chronic autoimmune hepaticdisorders, primary biliary cirrhosis or sclerosing cholangitis.