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

NCT06959108 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: GORTEC 2024-032023-510558-18-00
• Study Type: interventional
• Target: 106
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of this study is 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 MRG003 alone before chemoradiotherapy. People eligible to participate in this study must be between the ages of 18 and 75 and have locally advanced squamous cell carcinoma of the head and neck requiring treatment with chemoradiotherapy (cisplatin combined with radiotherapy). Half of the research participants will receive MRG003 alone as induction before radiochemotherapy and the other half will receive MRG003 combined with pucotenlimab as induction before radiochemotherapy, then pucotenlimab as adjuvant\* after radiochemotherapy.

Conditions

Locally Advanced Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• objective response rate

  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

  around 20 months after the inclusion of the 1st patient

Secondary Outcomes (3)

• Progression-free survival

  1 year from the inclusion of the last patient

• Failure-free survival

  1 year from the inclusion of the last patient

• Overall survival

  1 year from the inclusion of the last patient

Study Arms (2)

Pucotenlimab-MRG003

EXPERIMENTAL

* Induction treatment (9 weeks): 3 cycles of the anti-PD-1 Pucotenlimab in combination with the EGFR ADC MRG003 * Concurrent chemoradiation (7 weeks). The CRT will start within 28 ± 7 days after the Day 1 of the third cycle of the EGFR ADC MRG003. * Adjuvant treatment (24 weeks from one month after the end of CRT).

Drug: Pucotenlimab; Drug: MRG003

MRG003 alone

ACTIVE COMPARATOR

* Induction treatment ( 9 weeks): 3 cycles of the EGFR ADC MRG003 alone * Concurrent chemoradiation (7 weeks). The CRT will start within 28 ± 7 days after the Day 1 of the third cycle of the EGFR ADC MRG003.

Drug: MRG003

Interventions

Pucotenlimab DRUG

200mg every 3 weeks (21-day cycles) for a total of 3 cycles.

Pucotenlimab-MRG003

MRG003 DRUG

2.3 mg/kg, every 3 weeks (21-day cycles) for a total of 3 cycles.

MRG003 alone; Pucotenlimab-MRG003

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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) or magnetic 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 to NCICTCAE v.5
• No prior treatment with chemotherapy, immunotherapy and targeted therapy for H\&N cancer, radiotherapy or surgery in the head and neck region.

You may not qualify if:

• 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 targeting Tcell co-stimulation or checkpoint pathways).
• Treatment for other diseases with an investigational agent or use of an investigational device within 4 weeks of the first dose of study treatment
• 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 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: 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%.
• Patients with positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• 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.

Sponsors & Collaborators

• Groupe Oncologie Radiotherapie Tete et Cou: lead
• Lepu Medical Technology (Beijing) Co., Ltd.: collaborator

Study Officials

• Jean BOURHIS, Medical Director

  GORTEC

  STUDY DIRECTOR

Central Study Contacts

Marceline EMGOUE

CONTACT

02 42 06 02 56; marceline.emgoue@gortec.fr

Laura SINIGAGLIA

CONTACT

02 42 06 01 86

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2025
• First Posted: May 6, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): October 1, 2029
• Last Updated: September 2, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: At the end of the study and the delay will be defined in the contract
• Access Criteria: Researchers could be access to clinical data for participants