MRG003 alone or with the PD‑1 drug pucotenlimab before chemoradiotherapy for locally advanced head and neck squamous cell carcinoma
Randomized Phase 2 Trial of Induction Treatment of Anti-PD-1 Pucotenlimab and EGFR-ADC MRG003 Versus EGFR-ADC Alone Followed by Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma (LA-SCCHN).
This trial will test whether giving MRG003 alone or together with the PD‑1 drug pucotenlimab before standard chemoradiotherapy helps people with locally advanced head and neck squamous cell carcinoma.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 106 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | Groupe Oncologie Radiotherapie Tete et Cou Academic / other |
| Drugs / interventions | chemotherapy, immunotherapy, Pucotenlimab |
| Locations | 1 site (Villejuif) |
| Trial ID | NCT06959108 on ClinicalTrials.gov |
What this trial studies
Adults with locally advanced head and neck squamous cell carcinoma who are eligible for cisplatin-based chemoradiotherapy are assigned to one of two induction regimens prior to definitive radiochemotherapy. One group receives MRG003 (an EGFR-targeting antibody–drug conjugate) alone and the other receives MRG003 combined with the PD‑1 inhibitor pucotenlimab, with the combination arm continuing pucotenlimab after chemoradiotherapy. The main outcome is objective response rate measured by imaging per RECIST 1.1, and participants must have ECOG 0–1 and no prior systemic or head and neck radiation/surgery. Safety, tolerability, and subsequent disease control after chemoradiotherapy are also followed.
Who should consider this trial
Good fit: Adults aged 18–75 with locally advanced, nonmetastatic squamous cell carcinoma of the head and neck who are fit for cisplatin chemoradiotherapy (ECOG 0–1) and have not received prior systemic or head and neck radiation/surgery are ideal candidates.
Not a fit: Patients with metastatic (stage IVC) disease, prior checkpoint or similar immunotherapy, significant hearing loss (> grade 2), or who are not eligible for cisplatin are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, the combination could increase tumor shrinkage before chemoradiotherapy and potentially improve local control and longer‑term outcomes.
How similar studies have performed: Some prior studies combining EGFR-targeted agents or PD‑1 inhibitors with chemoradiation have shown activity in head and neck cancer, but combining an EGFR antibody–drug conjugate with a PD‑1 inhibitor in this induction setting is relatively novel and not yet proven.
Eligibility criteria
Show full inclusion / exclusion criteria
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) 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. 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 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.
Where this trial is running
Villejuif
- Gustave Roussy — Villejuif, France (Recruiting)
Study contacts
- Study coordinator: Marceline EMGOUE
- Email: marceline.emgoue@gortec.fr
- Phone: 02 42 06 02 56
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.