PUCOTENLIMAB for Locally advanced head and neck squamous cell carcinoma

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years, ≤ 75 years"}
• {"criterion_text":"- Patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1"}
• {"criterion_text":"- Histologically confirmed diagnosis in previously untreated LA-SCCHN patients suitable for definitive CRT : \tStage 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 \tIrrespective of tobacco consumption: T3-T4/N1-N3 p16 positive oropharyngeal squamous cell carcinoma (OPSCC) (p16 protein overexpression assessed by immunohistochemistry). Or \tOnly if tobacco consumption ≥ 20 pack - years: T1-T2/N1-N3 or T3-T4/N0 p16 positive OPSCC."}
• {"criterion_text":"- Evaluable tumor burden assessed by H&N-computed tomography scan (CT-scan) or magnetic resonance imaging (MRI), based on RECIST v 1.1"}
• {"criterion_text":"- Patients eligible to cisplatin-based chemotherapy"}
• {"criterion_text":"- No hearing loss by clinical assessment or ≤ grade 2 hearing impairment (according to NCI-CTCAE v.5)."}
• {"criterion_text":"- Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to randomization: a.\tPolynuclear neutrophils >1.5 x 109/L b.\tPlatelets > 100 x 109/L c.\tHemoglobin > 9.0 g/dL d.\tALAT/ASAT< 3.0 x ULN e.\tTotal bilirubin < 1.5 x ULN (except Gilbert Syndrome: < 3.0 mg/dL) f.\tGlomerular filtration rate ≥ 50 mL/min/1.73m² (using the CKD-EPI creatinine formula [see Appendix 4])"}
• {"criterion_text":"- No prior treatment with chemotherapy, immunotherapy and targeted therapy for H&N cancer, radiotherapy or surgery in the head and neck region."}

Exclusion criteria

• {"criterion_text":"- Metastatic disease (stage IVC as per AJCC/TNM, 8th Ed.)."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Treatment for other diseases with an investigational agent or use of an investigational device within 4 weeks of the first dose of study treatment."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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%."}
• {"criterion_text":"- Other active infections (viral and/or bacterial and/or mycotic) requiring systemic treatment at the day before randomization"}
• {"criterion_text":"- Documented weight loss of >10% during the last 4 weeks prior to randomization (unless adequate measures are undertaken for nutritional support)."}
• {"criterion_text":"- Patients with positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)."}
• {"criterion_text":"- 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"}

Primary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Investigator-assessed best objective response by head and neck radiological imaging according to RECIST v1.1 at end of induction phase (21 ± 7 days after Day 1 of last induction cycle). OR includes complete and partial responses."}

Secondary endpoints

• {"endpoint_text":"- •\tProgression-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.","definition_or_measurement_approach":"PFS defined as time from randomization to first progression (locoregional/metastatic after induction, CRT or adjuvant) or death from any cause; censored at last follow-up if no event."}
• {"endpoint_text":"- •\tFailure-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.","definition_or_measurement_approach":"FFS defined as time from randomization to first of: locoregional/metastatic progression after completion of CRT, failure to receive CRT, or death; censored at last follow-up if no event."}
• {"endpoint_text":"- •\tOverall survival (OS) defined as the time between randomization and death from any cause or date of the last follow-up for patients alive.","definition_or_measurement_approach":"OS defined as time from randomization to death from any cause; censored at last follow-up if alive."}
• {"endpoint_text":"- •\tCompliance: 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.","definition_or_measurement_approach":"Compliance measured by radiotherapy parameters (total tumor dose, fractions, duration, major deviations) and treatment parameters for anti-PD-1/EGFR-ADC/cisplatin (number of cycles/injections, total dose, duration, dose intensity, relative dose intensity); interruptions/reductions/discontinuations and reasons documented."}
• {"endpoint_text":"- •\tIncidence 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","definition_or_measurement_approach":"Safety assessed as incidence and severity of AEs, SAEs and laboratory abnormalities graded per NCI-CTCAE v5.0 from randomization to one month after end of adjuvant treatment."}

France

Earliest CTIS Part Ii Submission Date

26-05-2025

Latest Decision Or Authorization Date

24-06-2025

Processing Time Days

29

Number Of Sites

20

Number Of Participants

106

Primary sponsor

Full Name

Groupe Oncologie Radiotherapie Tete Cou

Organisation Type

Patient organisation/association

Country Of Registered Address

France