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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

Phase 2
Not yet recruiting
Conditions
Locally Advanced Head and Neck Squamous Cell Carcinoma
Interventions
Registration Number
NCT06959108
Lead Sponsor
Groupe Oncologie Radiotherapie Tete et Cou
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
106
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Pucotenlimab-MRG003Pucotenlimab* 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).
Pucotenlimab-MRG003MRG003* 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).
MRG003 aloneMRG003* 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.
Primary Outcome Measures
NameTimeMethod
objective response ratearound 20 months after the inclusion of the 1st patient

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

Secondary Outcome Measures
NameTimeMethod
Progression-free survival1 year from the inclusion of the last patient

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

Failure-free survival1 year from the inclusion of the last patient

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 case or the date of the last follow-up for patients who did not have these events

Overall survival1 year from the inclusion of the last patient

Overall survival (OS) defined as the time between randomization and death from any cause or date of the last follow-up for patients alive

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