Trial Title:
A Study to Evaluate MRG003 vs Cetuximab/Methotrexate in in the Treatment of Patients With RM-SCCHN
NCT ID:
NCT05751512
Condition:
Squamous Cell Carcinoma of the Head and Neck
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Methotrexate
Cetuximab
Conditions: Keywords:
MRG003
Antibody Drug Conjugate (ADC)
SCCHN
Study type:
Interventional
Study phase:
Phase 3
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
Description:
Administered intravenously
Arm group label:
MRG003
Intervention type:
Drug
Intervention name:
Cetuximab injection
Description:
Administered intravenously
Arm group label:
cetuximab/ methotrexate
Intervention type:
Drug
Intervention name:
Methotrexate Injection
Description:
Administered intravenously
Arm group label:
cetuximab/ methotrexate
Summary:
The objective of this study is to compare the efficacy and safety of MRG003 versus
cetuximab/methotrexate as second/third line of therapy in patients with RM-SCCHN who have
previously failed PD-1 (L1) inhibitors and platinum-based therapy.
Detailed description:
This is a randomized, open-label, multicenter Phase III study to compare the efficacy and
safety of MRG003 versus cetuximab/methotrexate as second/third line of therapy in
patients with RM-SCCHN who have previously failed PD-1 (L1) inhibitors and platinum-based
therapy. Approximately 180 patients will be enrolled, randomized, and stratified
according to the following: Eastern Cooperative Oncology Group Performance Status (ECOG
PS, 0 vs 1) and prior treatment with anti-EGFR mAb (yes vs no). For patients in the
control group, cetuximab will be selected as comparator if no prior treatment with
anti-EGFR mAb; otherwise, methotrexate will be selected.
After signing the informed consent and screened per inclusion/exclusion criteria,
eligible patients will be randomized at a ratio of 1 : 1 and treated with MRG003 (2.3
mg/kg, IV, d1, Q3W) or cetuximab (400 mg/m2 for the first week and 250 mg/m2 for
subsequent weeks, QW) / methotrexate (40 mg/m2, IV, QW) until disease progression, death,
intolerable toxicity, withdrawal of consent, initiation of a new anti-tumor therapy, or
other reasons leading to treatment discontinuation as specified by protocol.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
-
1. Understands and provides written informed consent and willing to follow the
requirements specified in protocol.
2. Age: ≥18 years and ≤75 years. 3. Life expectancy: ≥3 months. 4. Must have
histologically or cytologically confirmed recurrent or metastatic squamous cell
carcinoma of the head and neck (including oral cavity, oropharynx, hypopharynx,
larynx) who had previously failed PD-1 (L1) inhibitors and platinum-based therapy
(in combination or sequential). Prior therapies should be no more than 2 lines.
Note: If disease progression occurred during neoadjuvant/adjuvant treatment or concurrent
radiotherapy, or within 6 months after treatment discontinuation, the anti-tumor
therapies (including platinum-based chemotherapy, anti-EGFR monoclonal antibody, PD-1
(L1) inhibitors, etc.) during neoadjuvant/adjuvant treatment or concurrent radiotherapy
is counted as one line of prior treatment. Discontinuation or dose reduction of one drug,
or change of platinum- or fluorouracil-based agents or PD-1 (L1) inhibitors without
disease progression is considered as the same line of treatment.
5. Must have at least one measurable lesion per RECIST v1.1. Previously irradiated
lesion cannot be considered as target unless there is documented progression three
months after the last treatment of radiotherapy.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 1)
with no deterioration within 2 weeks prior to enrollment.
7. Adequate bone marrow function, defined as meeting all of the following criteria and
having no transfusion therapy within 3 weeks (21 days) or growth factors (G-CSF,
EPO, etc.) support within 2 weeks (14 days) prior to dosing:
• Hemoglobin (Hb) ≥ 9.0 g/dL (90 g/L)
• Absolute neutrophil count (ANC) ≥ 1,500/mcL (1.5 × 109/L)
• Total platelet count (PLT) ≥ 100,000/mcL (100 × 109/L) 8. Adequate hepatic function,
defined as all of the following:
• Total bilirubin (TBIL) ≤ 1.5×ULN;
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5×ULN if no
liver metastasis; ALT or AST ≤ 3.0×ULN in the presence of liver metastasis;
• Alkaline phosphatase (ALP) ≤ 1.5×ULN; ≤ 2×ULN in the presence of liver metastasis;
• Serum albumin ≥ 30 g/L 9. Coagulation: International Normalized Ratio (INR) or
prothrombin time (PT), activated partial thromboplastin time (APTT) ≤ 1.5×ULN (unless
patient is receiving anticoagulant therapy whose anticoagulant level should be within the
therapeutic range). The laboratory parameters should be closely monitored by investigator
if the patient is on anticoagulation therapy.
10. Adequate renal function, defined as Creatinine ≤ 1.5×ULN or creatinine clearance
rate (Ccr) ≥ 50 mL/min if Creatinine > 1.5×ULN (Creatinine clearance is calculated
using the modified Cockcroft-Gault equation. Creatinine clearance can be calculated
as Ccr = [(140-age) × body weight (kg) × (0.85 for women only)]/(72 × serum
creatinine) if no local guidelines are available (without significant electrolyte
imbalance that is not easily corrected).
11. Baseline Left Ventricular Ejection Fraction (LVEF) ≥ 50% measured by multiple-gated
acquisition (MUGA) or echocardiogram (ECHO).
12. A negative serum or urine pregnancy test within 7 days prior to the first dose of
study treatment (females of childbearing potential). If urine pregnancy test is
positive or cannot be confirmed as negative, a confirmatory serum pregnancy test is
required.
13. Patients, both females and males, of reproductive potential must agree to use
adequate contraception during study treatment and for 180 days after the last
treatment.
1. Females of childbearing potential (who are not surgically sterile or postmenopausal
for < 1 year) who are willing to use adequate and reliable contraception such as
avoidance of heterosexual activity, sterilization, oral contraceptives, injectable
contraceptives, intrauterine devices, condoms, etc., during the study until 180 days
after the last dose of study drug.
2. Male patients who are willing to use latex condoms during any sexual contact with
females of childbearing potential during treatment until 180 days after the last
treatment, even if vasectomy has been successfully performed. Reservation of semen
specimen prior to the first dose of study treatment is recommended for fertile males
for potential future conception.
Exclusion Criteria:
-
1. Grade ≥2 peripheral neuropathy per CTCAE v5.0. 2. Is expected to require
surgery or any other form of systemic or local anti-tumor therapy during
the study, including maintenance therapy or radiotherapy (including
palliative therapy, except for palliative therapy for non-target lesions)
for SCCHN.
3. Received systemic chemotherapy within 3 weeks, small molecule targeted
therapy within 2 weeks or 5 half-lives (whichever is longer), biological
anti-tumor therapy, macromolecule targeted therapy or immunotherapy within
4 weeks before the first dose of study treatment, or major surgery (except
for minor surgery within 2 weeks and fully recovered); radiotherapy
(except radiotherapy for CNS, wash-out period ≥ 28 days is required)
within 14 days before the first dose of study treatment.
4. Known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Patients with brain metastases may participate provided they
are treated and stable, and do not have the following:
- Progressive or new neurological deficits, seizures, evidence of increased
intracranial pressure, vomiting, or headache;
- Evidence of enlarging brain metastases by MRI at least 4 weeks prior to
the first dose and corticosteroids is required for at least 14 days prior
to study drug treatment.
5. Residual toxicities (except alopecia, fatigue, and Grade 2
hypothyroidism) due to prior anti-tumor therapy (including
immunotherapy, targeted therapy, chemotherapy or radiotherapy) or ≥
Grade 1 (CTCAE v5.0) clinically significant laboratory abnormality.
6. Uncontrolled or poorly controlled cardiac dysfunction, including
congestive heart failure (CHF) ≥ Grade 2 (CTCAE v5.0 or New York
Heart Association classification), history of myocardial infarction,
unstable angina pectoris, ventricular tachycardia or torsades de
pointes, or cardiac rhythm loss requiring treatment within 6 months
prior to enrollment, for example, QTcF > 450 ms in men, QTcF > 470 ms
in women, in presence of complete left bundle branch block or
third-degree atrioventricular block. QTcF = QT/ (RR^0.33).
7. Pulmonary embolism or deep venous thrombosis (except for thrombosis
caused by infusion port or PICC line) within 3 months prior to the
first dose of study drug.
8. Known history of malignancy (except for patients with cutaneous basal
cell carcinoma, superficial bladder carcinoma, cutaneous squamous
cell carcinoma, carcinoma in situ, or papillary thyroid carcinoma who
have undergone curative surgery) unless the patient has received
potentially curative therapy and has not had disease recurrence
within 5 years prior to study treatment.
Note: The 5-year recurrence-free time requirement does not apply to SCCHN patients
enrolled in this study.
9. Any serious or uncontrolled systemic disease, including uncontrolled or poorly
controlled hypertension (e.g., systolic blood pressure > 160 mmHg or diastolic
blood pressure > 100 mmHg), diabetes mellitus (glycosylated hemoglobin (HbA1c)
> 8%), etc.
10. Patients with active bleeding, history of coagulopathy, or receiving coumarin
anticoagulant therapy.
11. Known allergic reactions to any component or excipients of MRG003 (citric acid
monohydrate, sodium citrate dihydrate, trehalose dihydrate, sodium chloride,
and polysorbate 80) or known allergic reactions to other anti-EGFR agents
(including investigational drug) or to other monoclonal antibodies ≥ Grade 3.
12. Known active hepatitis B or C. Active hepatitis B is defined as known positive
HBsAg result and HBV DNA ≥ 500 IU/mL. Active hepatitis C is defined as known
positive hepatitis C antibody result and known quantitative hepatitis C virus
(HCV) RNA results greater than the lower limit of detection. Presence of other
serious liver diseases, including chronic autoimmune hepatic disorders, primary
biliary cirrhosis or sclerosing cholangitis, alcoholic liver disease, or
nonalcoholic steatohepatitis (NASH).
13. Concurrent, serious, uncontrolled infection or known infection with human
immunodeficiency virus (HIV) (HIV antibody positive), or diagnosis of acquired
immunodeficiency syndrome (AIDS); or uncontrolled autoimmune disease; or
previous allogeneic tissue/organ transplantation, stem cell or bone marrow
transplantation, or previous solid organ transplantation.
14. Active bacterial, viral, fungal, rickettsial, or parasitic infection requiring
systemic anti-infection therapy (unless treated and resolved prior to study
treatment).
15. Received live-virus vaccines within 30 days prior to the first dose of study
treatment. Seasonal influenza vaccines or approved COVID-19 vaccines that do
not contain live virus are permitted if vaccinated more than 1 week before the
first dose of study treatment.
16. History of interstitial pneumonia, severe chronic obstructive pulmonary disease
with respiratory failure, severe pulmonary insufficiency, symptomatic
bronchospasm, etc.
17. Patients who are receiving an immunologically based treatment for any reason,
including chronic use of systemic steroids equivalent to > 10 mg/day of
prednisone within 7 days prior to the first dose of study treatment or at any
time during the study. Note: Use of inhaled or topical steroids or systemic
corticosteroids equivalent to ≤ 10 mg/day prednisone is permitted, as is
short-term use of corticosteroids at doses equivalent to > 10 mg/day prednisone
(e.g., pre-medication prior to contrast).
18. Uncontrolled pleural, abdominal, pelvic effusion or pericardial effusion that
requires ≥ 1 drainage per month.
19. Any patient with a positive pregnancy or is breast-feeding. Female and male
patients who are not expected to use adequate contraception during treatment
and for 180 days after the last dose of treatment.
20. Any other disease or clinically significant abnormality in laboratory
parameters, or serious medical or psychiatric illnesses/conditions, substance
abuse disorder including alcoholism, which in the judgment of the Investigator
might compromise the safety of the patient, integrity of the study, interfere
with the patient participation in the study, or confound or compromise the
study objectives and their interpretability.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Shanghai East Hospital
Address:
City:
Shanghai
Zip:
200123
Country:
China
Contact:
Last name:
Ye Guo
Email:
pattrickguo@gmail.com
Start date:
March 2023
Completion date:
December 2025
Lead sponsor:
Agency:
Shanghai Miracogen Inc.
Agency class:
Industry
Source:
Shanghai Miracogen Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05751512
