Trial Title:
A Phase II Study of MRG003 Injection Combined With Pucotenlimab Injection ± Cisplatin Injection in the Neoadjuvant Treatment Locally Advanced EGFR-positive Head and Neck Squamous Cell Carcinoma
NCT ID:
NCT06530914
Condition:
Head and Neck Squamous Cell Carcinoma (HNSCC)
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Cisplatin
Conditions: Keywords:
Locally Advanced EGFR-positive HNSCC
Neoadjuvant therapy
Antibody-drug conjugate
immunotherapy
chemotherapy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
MRG003 combined with Pucotenlimab
Description:
Both interventions all drugs intravenous infusion, D1, once every 3 weeks, a total of 3
cycles.
Arm group label:
MRG003+Pucotenlimab
Other name:
MRG003+Pucotenlimab
Intervention type:
Drug
Intervention name:
MRG003 combined with Pucotenlimab+Cisplatin
Description:
All interventions all drugs intravenous infusion, once every 3 weeks, a total of 3
cycles.
Arm group label:
MRG003+Pucotenlimab+Cisplatin
Other name:
MRG003+Pucotenlimab+Cisplatin
Summary:
A Randomized, Phase II Study of MRG003 in Combination With Pucotenlimab Injection ±
Cisplatin in Patients With Locally Advanced EGFR-positive Head and Neck Squamous Cell
Carcinoma. This proposed study will evaluate the efficacy and safety of preoperative
administration of MRG003 in Combination With Pucotenlimab Injection ± Cisplatin in HNSCC
who are eligible for resection.
Detailed description:
In this study, eligible patients will be randomized in a 1:1 ratio to either the MRG003
Injection Combined With Pucotenlimab Injection treatment group (Cohort 1), or the MRG003
Injection Combined With Pucotenlimab Injection + Cisplatin treatment group (Cohort 2).
Pathological response rate will be the primary outcome measures. Adverse events will also
be recorded.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Sign the informed consent voluntarily and follow the requirements of the program;
2. Age ≥18 years old, ≤70 years old, gender is not limited;
3. Physical condition score ECOG 0 or 1;
4. Histopathology confirmed the diagnosis of head and neck squamous cell carcinoma, and
immunohistochemistry confirmed that EGFR expression was positive (defined as weak
staining of > 10% of tumor cells);
5. No previous treatment for head and neck squamous cell carcinoma, including drug
therapy, radiotherapy, surgery, etc., and the tumors of the subjects assessed by the
researchers before admission could be surgically resected;
6. According to the American Joint Committee on Cancer (AJCC) /TNM Staging System
eighth Edition, patients must have the following tumor stages: 1) patients with
stage III, IVA, and IVB non-oropharyngeal cancer and patients with HPV-negative
oropharyngeal cancer; Or 2) Stage II and III HPV-positive oropharyngeal cancer
patients. For patients with oropharyngeal cancer, HPV status should be determined by
p16 IHC.
7. The level of organ function must meet the following requirements:
- Bone marrow: absolute neutrophil count (ANC) ≥1.5×109/L, platelet count
≥100×109/L, hemoglobin ≥90 g/L, and no blood transfusion or biological response
regulator (such as granulocyte, erythrocyte growth factor, etc.) treatment
within 14 days before the first dose;
- Liver: total bilirubin (TBIL) ≤1.5×ULN; Alanine aminotransferase (ALT),
aspartate aminotransferase (AST) and alkaline phosphatase (ALP) ≤2.5×ULN; Serum
albumin ≥28 g/L;
- Kidney: creatinine clearance (Ccr) ≥50 mL/min (according to Cockcroft and Gault
formula);
- Coagulation function: International standardized ratio (INR) ≤1.5×ULN, and
activated partial thromboplastin time (APTT) ≤1.5×ULN (except those receiving
therapeutic anticoagulants);
- No severe cardiac dysfunction, left ventricular ejection fraction (LVEF) ≥50%;
8. Fertile men and women of childbearing age are willing to take effective
contraceptive measures from the signing of informed consent to 6 months after the
last administration of the experimental drug; Women of reproductive age include
premenopausal women and women within 1 year after menopause. Blood pregnancy test
results for women of childbearing age must be negative within ≤7 days before the
first trial drug administration.
Exclusion Criteria:
1. Tumors originating from nasopharyngeal, paranasal, nasal or salivary glands, thyroid
or parathyroid lesions, skin, unknown primary squamous cell carcinoma or
non-squamous histology (e.g., mucosal melanoma);
2. Peripheral neuropathy ≥ grade 2 (according to CTCAE v5.0);
3. Have received any of the following treatments:
- Received intravenous antibiotic therapy within 7 days prior to initial dosing;
- Investigational drugs that have received other clinical trials within 4 weeks
prior to initial dosing;
- have received live attenuated vaccine within 4 weeks prior to first
administration, and are allowed to receive inactivated seasonal influenza
vaccine or approved COVID-19 vaccine without live virus;
- Received systemic immunostimulatory drugs (including but not limited to
interferon, interleukin-2, etc.) within 4 weeks prior to initial
administration;
- Had major surgery (e.g., transabdominal, thoracic, etc., excluding diagnostic
puncture, infusion device implantation, or digestive home implantation) within
4 weeks prior to initial dosing, or expected to require major surgery during
the study period; Previous immunotherapy with anti-PD-1, anti-PD-L1,
anti-PD-L2, anti-CD137 or anti-CTLA-4 antibodies (including ipilimumab) or any
other antibody or drug that targets T-cell co-stimulation or immune checkpoint
pathways;
4. A history of other primary malignancies within the past 3 years, excluding basal
cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of
the skin, or cervical carcinoma in situ that has been completely and radically
resected;
5. Clinically significant (i.e., active) cardiovascular disease: cerebrovascular
accident/stroke/myocardial infarction, unstable angina, congestive heart failure
(NYHA Class II and above), or severe arrhythmia requiring medication within the
first 6 months of enrollment;
6. Evidence of active infection includes hepatitis B (HBsAg positive with HBV DNA≥2000
IU/ml, excluding hepatitis due to drugs or other causes), hepatitis C (HCV positive
with anti-HCV antibody), hepatitis B (HCV positive with HBV DNA≥2000 IU/ mL), and
hepatitis C (HCV positive with HBV DNA≥2000 IU/ mL). HCV RNA results greater than
the lower limit of detection) or human immunodeficiency virus (HIV) infection;
Uncontrolled active bacterial, other viral, fungal, rickettsial, or parasitic
infections, unless treated and resolved prior to administration of the
investigational drug;
7. Loss of more than 10% of body weight in the 4 weeks prior to the first dose (unless
appropriate nutritional support measures are taken);
8. Active gastrointestinal bleeding, or bleeding requiring more than 2 red blood cell
transfusions or 4 units of compressed red blood cell transfusions within the first 4
weeks;
9. Patients with a history of primary immunodeficiency or active autoimmune disease who
were taking immunosuppressants or systemic hormone therapy (dose ≥10 mg/ day of
prednisone or other equivalent hormone) and continued to use it within 2 weeks prior
to enrollment; Attention: Patients with type I diabetes, stable hypothyroidism with
hormone replacement therapy (including hypothyroidism due to autoimmune thyroid
disease), psoriasis, vitiligo, or psoriasis that does not require systemic treatment
may be enrolled with topical or inhaled corticosteroids, or short-term (≤7 days)
corticosteroids for prevention or treatment of non-autoimmune diseases. And
infrequent allergic diseases are excluded. ;
10. A history of grade 3 allergy to any component of MRG003, Ptrelizumab injection,
and/or cisplatin injection;
11. Previous history of interstitial pneumonia, radiation pneumonia, severe chronic
obstructive pulmonary disease, severe pulmonary insufficiency, symptomatic
bronchospasm, etc.;
12. History of organ transplantation, including allogeneic peripheral stem cell or bone
marrow transplantation. After careful evaluation, patients who received autologous
hematopoietic stem cell transplantation (HSTC) ≥ 5 years ago and who have normal
bone marrow function (independent of transfusion) may be considered for study
participation;
13. Other conditions deemed unsuitable for participation in this clinical trial by the
investigator, including but not limited to serious mental illness, central nervous
disorder, substance abuse, etc.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Start date:
August 1, 2024
Completion date:
December 31, 2027
Lead sponsor:
Agency:
Lei Liu
Agency class:
Other
Source:
West China Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06530914
