| Eligibility |
Inclusion Criteria:
1. A female patient aged 19 or older at the time of signing the informed consent
2. Histologically identified, resectable local progressive, HPV positive (positive in p16
immunohistochemistry and positive in HPV-16 and/or HPV-18 nucleic acid tests) LA HNSCC
patients
3. A patient has never received other chemotherapy before
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
5. Life expectancy of > 6 months
6. Patient agreed to provide storage tumor tissue samples or fresh biopsy samples for
baseline biomarker tissue analysis including PD-L1 staining during biopsy or surgery
must be present. If there is no storage tissue and there is no tumor lesion that can
be sampled from biopsy or surgery, it will be excluded from the test.
7. Patients with suitable organ function as defined in Table 1 below should be patients.
Samples must be collected within 28 days prior to the initiation of clinical trial
drugs.
< Requirements for long-term function for conformity evaluation > Laboratory
examination of the body organs [Hematology] Absolute neutrophil count (ANC) =1,500/µL
Platelet count =100,000/µLHemoglobin =9.0 g/dL [Kidney] Measurement or calculation of
creatinine or creatinine cleaning rate 2 (GFR may be used instead of creatinine or
CrCl) =1.5 × ULN or, creatinine >1.5x (If you're a test subject of ULN) =30 mL/min
[Liver]Serum total bilirubin =1.5 × ULN or, total bilirubin >1.5 x (If you're a test
subject of ULN) direct bilirubin =ULN (This will not apply to patients with confirmed
Gilbert's syndrome, total bilirubin <3x ULN and ALT<3xULN) AST (SGOT)/ALT (SGPT) =2.5
x institutional upper limit of normal unless liver metastases are present, in which
case it must be =5x ULN [Blood coagulation] INR or prothrombin Time(PT), Activation
TromboplastinTime(aPTT)
- 1.5 × Unless ULN, PT or aPTT is within the scope of treatment for the intended
anticoagulant use, the patient is not receiving anticoagulant therapy
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ALT (SGPT)= alanine aminotransferase, serum glutamic pyruvic transaminase; AST
(SGOT)= aspartate aminotransferase serum glutamic oxaloacetic transaminase;
GFR(glomerular filtration rate); ULN=normal range , upper limit of normal
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1. It must meet the criteria without dependence on red blood cells within the
past 4 weeks and without receiving concentrated red blood cell (pRBC) blood
transfusions.
2. Measured creatinine clearance (CrCl) by the Cockcroft-Gault formula
(Cockcroft and Gault 1976)
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8. Patient with RECIST measurable diseases defined as below:
Tumor lesions with a long axis diameter (LD) =1 cm in axial CT or MRI images
(restoration interval =5 mm) or lymph node =1.5 cm in short axis CT (restoration
interval 5 mm)
9. For fertile woman (WOCBP), patient with negative results of serum or urine pregnancy
tests conducted within 72 hours prior to the first administration of clinical trial
drugs. If the urine test result is positive or cannot be confirmed negative, a serum
pregnancy test should be performed.
10. Fertile woman must agree to use appropriate double contraception by 120 days after the
entire course of this trial and the last administration of clinical trial drugs. Woman
who are menopause (over 45 years of age and have no menstruation for more than a year)
and women who are surgically infertile are exempt from this requirement.
Note: abstinence is permitted if it is the daily lifestyle of the test subject and the
contraceptive method preferred by the test subject.
11. Patient is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
up.
Exclusion Criteria:
1. Irresectable metastatic or recurrent cancer
2. Patients who are currently in progress or have been confirmed to have other malignant
diseases that required active treatment within the past three years..
Note: Subjects with skin basal cell carcinoma, skin squamous cell carcinoma, or in
situ carcinoma (e.g., breast cancer) that have been treated for potential complete
recovery purposes are not excluded.
3. Patients expected to require other forms of anti-neoplasm therapy during the test;
This treatment includes systemic chemotherapy, radiation therapy, biotherapy, or
immunotherapy not specified in the protocol.
4. Patients with a history of active central nervous system (CNS) metastasis and/or
carcinoma meningitis.Patients with asymptomatic or controlled CNS metastasis
5. Patients who have previously received treatment using anti-PD-1, anti-PD-L1, or
anti-PD-L2 drugs or have received treatment using drugs directly acting on other
irritating or co-inhibitory T cell receptors (e.g., CTLA-4, OX40, CD137).
6. Patients suffering from active autoimmune diseases requiring systemic
immunosuppressive treatment (e.g., use of disease modulators, corticosteroids, or
immunosuppressants) within the past two years. Alternative therapy (e.g., thyroxine,
insulin, or physiological corticosteroid replacement due to adrenal or pituitary
dysfunction) is not considered a form of systemic therapy and is therefore acceptable.
7. Patients who received homogeneous solid organ transplantation or homogeneous bone
marrow transplantation
8. Patients who have been administered non-PD-1/PD-L1/PD-L2, anti-cancer monoclonal
antibodies (mAb, e.g., bevacizumab, cetuxizumab, etc.) within 4 weeks prior to the
first administration of the clinical trial drug or have not yet recovered (e.g., grade
1 or baseline level).
9. Patients who received systemic chemotherapy including other clinical trial drugs
within 4 weeks before the first administration of this clinical trial drug or received
targeted hypogermic therapy with a half-life of less than 48 hours within 2 weeks
. Note: The subject must have recovered to the baseline level or below in all adverse
reactions caused by previous treatment. Neuropathy under grade 2 and/or anemia under
grade 2 may be suitable.
Note: If the subject has undergone major surgery, the subject must be properly
recovered from toxicity and/or complications caused by the intervention prior to
commencement of treatment.
10. Patients who had received radiation therapy within two weeks prior to the initiation
of clinical trial drugs. The test subjects must have recovered from all
radiation-related toxicity.
11. Patients who have transfused blood products (including platelets or red blood cells)
within 4 weeks before the first administration of clinical trial drugs or have
administered colony stimulation factors (Includes G-CSF, GM-CSF, or recombinant red
blood cell generators).
12. Patients with bilateral hydronephrosis that cannot be alleviated by ureteral stent or
percutaneous renal fistula formation.
13. Patients with severe (=3) hypersensitivity to one of the additive components of
pembrolizumab and/or
14. Patients with a history of (non-infectious) interstitial pneumonia requiring steroids
or currently suffers from interstitial pneumonia.
15. Patients diagnosed with immunodeficiency or patients receiving long-term systemic
steroid therapy (dose exceeding 10 mg of prednisone per day) or receiving other
immunosuppressive treatments in any form within 7 days prior to the first
administration of clinical trials.
16. Patients with risk factors for intestinal obstruction or intestinal perforation (e.g.,
acute diverticulitis, intraabdominal abscess, and abdominal carcinoma, but not
limited).
17. Patients who are currently participating in clinical trials for other clinical trial
drugs or have participated in the past have received clinical trial treatment or used
clinical trial devices within 4 weeks before the first administration of this clinical
trial drug.
Note: If more than 4 weeks have elapsed since the last administration of the previous
clinical trial drug, subjects who have entered the follow-up stage of the clinical
trial may participate in this trial.
18. Unstable/Inadequate heart function:
- symptomatic ischemia
- Unregulated or clinically significant abnormal conduction (e.g., ventricular
tachycardia during antiarrhythmia treatment); 1-degree ventricular block or
asymptomatic LAFB/RBB is suitable
- Cardiomyopathy within the past 6 months.
- Congestion Heart failure (New York Heart Association III - IV grade)
19. Active infected patients who need systemic treatment
20. Patients with confirmed human immunodeficiency virus (HIV) infection, and/or hepatitis
B or C history, or hepatitis B surface antigen (HBsAg)/ hepatitis B virus (HBV) DNA or
hepatitis C antibody or RNA test positive. Active hepatitis C is defined as a case
where Hep CAb results are positive and quantitative HCV RNA results are found to be
higher than the lower detection limit of the analysis.
21. Patients with a history of active tuberculosis (TB, Bacillus Tuberculosis)
22. Patients who received a live vaccine within 30 days before the first administration of
the clinical trial drug. Examples of live vaccines include, but are not limited to,
the following: Measles, mumps, rubella, pox/shingles, yellow fever, rabies, BCG, and
typhoid vaccines. Seasonal flu vaccines used in injections are generally viral
vaccines, but nasal flu vaccines (e.g., Flumist®) are not allowed because they are
weakly poisoned vaccines.
23. Patients who have been confirmed to have mental illness or substance abuse that may
interfere with their ability to cooperate with the requirements of this test.
24. A patient who transplanted an implantation electronic device (e.g., a pacemaker) into
the body.
25. Fertile women with positive urine pregnancy test results (e.g., within 72 hours) prior
to administration of clinical trial drugs. If the urine test is positive or has not
been confirmed negative, a serum pregnancy test is required.
26. Pregnant or lactating patient
27. Patients who are likely to confuse the test results or interfere with the subject's
participation in the entire duration of the test. Patients who have a history of
abnormalities in conditions, treatments, laboratory tests, or currently have such
evidence, regardless of type, where participation in clinical trials is judged to be
in the best interest of the subjects.
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