Evaluate the Efficacy and Safety of HLX10 in Combination With HLX07 in Patients With Advanced Head and Neck Tumors
Evaluate the Efficacy and Safety of HLX10 in Combination With HLX07 in Patients With Advanced Head and Neck Tumors
A mutilpe-center, open-label, Phase II clinical trial to evaluate the efficacy and the safety
 of HLX10 in combination with HLX07 in patients with advanced advanced head and neck tumors
This is an open label study. Sample size recommendations for this phase II study are
 determined according to Simon's two-stage Optimal design.

 In the first stage, 13 patients will be accrued. The patients will receive 3 mg/kg of HLX10
 every two weeks infusion combined with 600 mg HLX07 weekly (stage 1L). These patients will be
 assessed for treatment response after 8 weeks of first infusion of study drugs. If there are
 3 or fewer responsive patients in these 13 patients, additional 13 patients will be accrued.
 These additional 13 patients will receive 3 mg/kg of HLX10 every two weeks infusion combined
 with 800 mg HLX07 weekly (Stage 1H). If 3 or fewer responses after eight weeks treatment
 noted in these 13 patients in stage 1H, the trial will be stopped.

 If 4 or more patients are responsive to therapy in stage 1, the trial will be continued to
 stage 2, 30 additional patients will be accrued to reach a total of 43 patients. These
 additional 30 patients will receive the same dose of regimen as the prior patients.
Inclusion Criteria:

 1. Eligible patients must be 18 years of age or older or per local regulation AND younger
 than 80 years old age.

 2. Patients with histologically-proven recurrent (not amenable to locally curative
 treatment options) or metastatic, squamous cell carcinoma of the head and neck with
 previously failed platinum-based chemotherapy and PD-L1 expression (combined positive
 score ≥ 1) as determined by immunohistochemistry (IHC) stain. (Patient must be able to
 provide tissue for PD-L1 biomarker analysis from a core or excisional biopsy; fine
 needle aspirate is not sufficient.: A newly obtained biopsy; within 90 days prior to
 start of study treatment; is preferred but an archival sample is acceptable.)

 3. Lesion must be measurable based on RECIST, version 1.1.

 4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 at the time of
 study entry.

 5. Able to provide informed consent.

 6. A life expectancy longer than three months.

 7. Adequate hematologic functions, as defined by: absolute neutrophil counts (ANC) ≥
 1500/mm3; a hemoglobin (Hb) level ≥ 9 gm/dL; a platelet count ≥ 100,000/mm3.

 8. Adequate hepatic function defined by: a total bilirubin level ≤ 1.5x of upper limit of
 normal (ULN); aspartate transaminase (AST) and alanine transaminase (ALT) levels ≤ 2.5
 x of ULN or ≤ 5x of ULN in known hepatic metastases.

 9. Adequate renal function, as defined by the creatinine clearance rate ≥ 50 mL/minute
 calculated using Cockcroft-Gault formula. In patient with extreme body weight (body
 mass index [BMI] < 18.5 or > 30), estimated glomerular filtration rate (GFR) ≥
 50mL/min calculated using Modification of Diet in Renal Disease (MDRD) formula is
 acceptable.

 10. Adequate cardiac function defined as left ventricular ejection fraction (LVEF) ≥ 50%
 measured by multigated acquisition (MUGA) scan or cardiac ultrasound.

 11. Use of effective contraceptive measures if procreative potential exists .

 12. At least 28 days from prior major surgery, prior cytotoxic chemotherapy, or prior
 therapy with investigational agents (or medical device) and curative radiotherapy or
 palliative radiotherapy to target lesion before the first infusion of investigational
 product.

 13. Able to follow the procedures as required by the study protocol and must agree to
 provide tumor tissue for programmed cell death 1 (PD-L1) expression analyses, EGFR
 mutation status, and biomarker assessment.

 Exclusion Criteria:

 1. Patients who still have persistent ≥ grade 2 toxicities from prior therapies.

 2. Patients with primary nasopharynx cancers.

 3. Squamous cell carcinoma of unknown primary in cervical lymph node.

 4. Concurrent unstable or uncontrolled medical conditions. Either of the followings:

 -  Active systemic infections currently under treatment with antimicrobial agents;

 -  Poorly controlled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic
 blood pressure ≥100 mmHg), or poor compliance with anti-hypertensive agents;

 -  Clinically significant arrhythmia, unstable angina pectoris, congestive heart
 failure (class III or IV of New York Heart Association [NYHA]) or acute
 myocardial infarction within 12 months;

 -  Uncontrolled diabetes or poor compliance with hypoglycemic agents;

 -  The presence of chronically unhealed wound or ulcers;

 -  Other chronic diseases, which, in the opinion of the investigator, could
 compromise safety of the patient or the integrity of study.

 5. Newly-diagnosed or symptomatic brain metastases (patients with a history of brain
 metastases must have received definitive surgery or radiotherapy, must be clinically
 stable, and must not taking steroids for brain edema for at least 14 days to be
 allowed in the study). Anticonvulsants are allowed.

 6. Any concurrent malignancy other than basal cell carcinoma or carcinoma in situ of the
 cervix. (Patients with a previous malignancy but without evidence of disease for ≥ 3
 years can participate).

 7. Pregnancy (confirmed by serum beta human chorionic gonadotropin [ßHCG]) or
 breast-feeding.

 8. Known history of human immunodeficiency virus infection (HIV).

 9. Patient who has an active or a documented history of autoimmune disease.

 10. Patient who has active hepatitis B (HBV DNA titer > 100 IU/mL or > 500 copies/mL) or
 hepatitis C (defined as anti-HCV antibody reactive and/ or detectable HCV RNA > 15
 IU/L).

 11. Patient who has a history of interstitial lung disease.

 12. Have a condition requiring systemic treatment with either corticosteroids (> 10 mg
 daily prednisone equivalents) or other immunosuppressive medications within 14 days of
 study drug administration. Inhaled or topical steroids and adrenal replacement doses >
 10 mg daily prednisone equivalents are permitted in the absence of autoimmune disease.

 13. Patients who have failed systemic anti-EGFR monoclonal antibody therapies (who have PD
 or PFS less than 3 months during anti EGFR treatment) or have been received more than
 3 lines of systemic chemotherapy regimens.

 14. Patients who previously have severe allergic reaction to anti-EGFR monoclonal antibody
 (CTCAE grade ≥3).

 15. Patients who have previously received immune check point therapy, including but not
 limit to anti-PD1 and anti-PDL1.

 16. The patient is the investigator, sub-investigator or any one directly involved in the
 conduct of the study.

 17. Patient has a history or current evidence of any condition or disease that could
 confound the results of the study, or study or is not the best interest of the patient
 to participate, in the opinion of Investigator.