Trial Title:
A Phase II Study of Anti-EGFR Antibody-drug Conjugate (ADC) Combine With CDK4/6 Inhibitors Posterior Line in the Treatment of Recurrent/Metastatic CDKN2A Gene Variant Head and Neck Squamous Cell Carcinoma
NCT ID:
NCT06509997
Condition:
Head and Neck Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Conditions: Keywords:
Recurrent/metastatic head and neck squamous cell carcinoma
CDKN2A gene variant
CDK4/6 inhibitor
Antibody-drug conjugate
EGFR inhibitor
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
A single-arm Phase II clinical trial
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
MRG003 combined with Dalpicicilip
Description:
MRG003, intravenous infusion, D1, once every 3 weeks; Dalpicicilip, taking orally, D1-21,
once every 4 weeks, maintain use until progression or emergence of intolerable toxicity.
Arm group label:
MRG003+Dalpicicilip
Summary:
A Single-arm, Phase II Study of MRG003 combined with Dalpicicilip posterior line in the
treatment of recurrent/metastatic CDKN2A gene variant head and neck squamous cell
carcinoman (HNSCC). The objective of this study was to evaluate the safety and efficacy
of MRG003 combined with the Dalpicicilip posterior line in the treatment of
recurrent/metastatic CDKN2A gene variant HNSCC.
Detailed description:
In this study, patients meeting the inclusion criteria were given MRG003 (D1, IVGTT, Q3W)
in combination with Darcilil (D1-21, PO, Q4W) after completing the relevant pre-treatment
examination until progression or intolerable toxicity occurred. Objective response rate
and safety will be the primary outcome measures. Adverse events will also be recorded.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. 18 years old ≤75 years old;
2. Patients with recurrent or metastatic head and neck squamous cell carcinoma
(including oral cavity, oropharynx, hypopharynx, larynx, etc.) confirmed by
histology or cytology, recurrent patients cannot receive local treatment such as
surgery or radiotherapy, and have failed to receive PD-1 (L1) inhibitors and/or
platinum drugs in the past, which can be first-line combination regimens or
sequential administration. Progression after receiving PD-1 (L1) inhibitors and/or
platinum-based drugs;
3. Receive ≤2 lines of treatment;
4. ECOG score 0~1;
5. Lack of CDKN2A function;
6. At least one evaluable lesion according to RECIST (version 1.1) criteria;
7. Adequate organ function;
8. The expected survival time is greater than 3 months;
9. No serious organic heart disease or arrhythmia;
10. Women of childbearing age (15-49 years) must undergo a pregnancy study within 7 days
before starting treatment and the results are negative; Fertile men and women must
consent to the use of effective contraception to ensure that they do not become
pregnant during the study period and for 3 months after stopping treatment;
11. Obtain the "informed consent" voluntarily signed by the patient.
Exclusion Criteria:
1. ≥ grade 2 peripheral neuropathy (according to CTCAE 5.0).
2. Surgery or any other form of systemic or local anti-tumor therapy, including
maintenance therapy or radiotherapy for head and neck squamous cell carcinoma
(including palliative care, except palliative care for non-target lesions), is
expected to be required during the study period.
3. Systematic chemotherapy was received within 3 weeks before the first administration
of the drug, small molecule targeted therapy was received within 2 weeks before the
first administration or 5 half-lives (depending on the time), antitumor biotherapy,
macromolecule targeted therapy or immunotherapy was received within 4 weeks before
the first administration of the drug. Or major surgery (except minor surgery
performed within 2 weeks and complete recovery); Radiotherapy was received within 14
days prior to initial administration of the investigational drug (except for central
nervous system radiotherapy, which required a washout period of ≥28 days).
4. Known to have active central nervous system metastasis and/or cancerous meningitis.
Patients with treated BMS may participate in the study if their condition is stable
and they do not:
- Progressive or new neurological deficits, seizures, evidence of increased
intracranial pressure, vomiting, or headache;
- MRI shows evidence of enlargement at least 4 weeks before first dosing and at
least 14 days before study drug dosing Corticosteroids are required.
5. Residual toxic effects (except alopecia, fatigue and grade 2 hypothyroidism) caused
by previous antitumor therapy (including immunotherapy, targeted therapy,
chemotherapy or radiotherapy) or clinically significant laboratory test outliers
higher than grade 1 (CTCAE v5.0).
6. Uncontrolled or poorly controlled heart disease, including a history of congestive
heart failure (CHF) ≥2 (CTCAE v5.0 or New York Heart Association rating), myocardial
infarction, unstable angina, ventricular tachycardia or tip twisting ventricular
tachycardia, or arrhythmias requiring treatment within the 6 months prior to
admission, For example, men with QTcF > 450 ms and women with QTcF > 470 ms have
complete left bundle branch block or third-degree atrioventricular block. QTcF= QT/
(RR^0.33).
7. Pulmonary embolism or deep vein thrombosis (except for catheter-derived thrombosis
at infusion port or PICC) occurred within 3 months prior to the first administration
of the drug.
8. There is a known prior history of malignancy (except in patients with basal cell
carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the
skin, carcinoma in situ, or papillary carcinoma of the thyroid who have undergone
radical surgery), unless the patient has received potentially curable therapy and
has been free of disease recurrence for 5 years since starting treatment. Note: The
5-year recurrence-free time requirement does not apply to head and neck squamous
cell carcinoma in patients enrolled in this trial.
9. Any serious or uncontrolled systemic disease, including uncontrolled or poorly
controlled hypertension (such as systolic blood pressure >160 mmHg or diastolic
blood pressure >100 mmHg), glycosuria (glycated blood red and egg white (HbA1c)
>8%), etc.
10. Patients with a history of active bleeding, clotting disorders, or receiving
coumarin anticoagulant therapy.
11. Known allergic reactions to any component or excipient of MRG003 (citric acid
monohydrate, sodium citrate dihydrate, trehalose dihydrate, sodium chloride and
polysorbate 80), or grade ≥3 allergic reactions to other prior anti-EGFR drugs
(including investigational drugs) or to other monoclonal antibodies.
12. Known active hepatitis B or C. Active hepatitis B is defined as known HBsAg positive
and HBV DNA≥500 IU/mL. Active hepatitis C is defined as a known positive hepatitis C
antibody and a known quantitative hepatitis C virus HCV RNA result greater than the
lower limit of detection. Other serious liver diseases are present, including
chronic autoimmune liver disease, primary biliary cirrhosis or sclerosing
cholangitis, alcoholic liver disease, or non-alcoholic steatohepatitis (NASH).
13. Concurrent severe, uncontrolled infection or known human immunodeficiency virus
(HIV) (HIV antibody positive) infection, or a diagnosis of acquired immune
deficiency syndrome (AIDS); Or uncontrolled autoimmune disease; Have previously
received an allogeneic tissue/organ transplant, stem cell or bone marrow transplant,
or have previously received a solid organ transplant.
14. Active bacterial, viral, fungal, rickettsial, or parasitic infections requiring
systemic anti-infective therapy (unless treatment is obtained and resolves prior to
administration of the investigational drug).
15. The live virus vaccine was administered within 30 days prior to the first
administration of the investigational drug. Seasonal influenza vaccines or approved
COVID-19 vaccines that allow the use of inactivated viruses must be at least one
week from the time of first administration.
16. A history of interstitial pneumonia, severe chronic obstructive pulmonary disease
with respiratory failure, severe pulmonary insufficiency, and symptomatic
bronchospasm.
17. Immunological based treatment for any reason, including long-term use of a systemic
steroid equivalent to >10 mg/ day of prednisone within 7 days before the first
administration of the study drug or at any time during study participation. Note:
Inhaled or topical steroids or systemic corticosteroids equivalent to ≤10 mg/ day of
prednisone are permitted, as are short-term corticosteroids equivalent to >10 mg/
day of prednisone (e.g., prodromal administration before contrast agent
administration).
18. Uncontrolled pleural, abdominal, pelvic or pericardial effusions require drainage ≥
once a month.
19. Patients who have tested positive for pregnancy or are breastfeeding. Women and men
who do not plan to use adequate contraception during treatment and within 180 days
after the last treatment.
20. Any other illness or clinically significant laboratory parameter abnormality,
serious medical or psychiatric illness/condition, and substance abuse, including
alcohol abuse, that the investigator believes could compromise patient safety, study
integrity, affect patient participation in the study or interfere with the purpose
of the study and analysis of the results.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 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/NCT06509997
