Evaluate the Efficacy and Safety of HLX10 in Combination With HLX07 in Patients With Advanced Head and Neck Tumors
Study Details
Study Description
Brief Summary
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: HLX10 Plus HLX07 (stage 1L) 3 mg/kg of HLX10 every two weeks infusion combined with 600 mg HLX07 weekly |
Drug: Experimental: Stage 1L: HLX10 Plus HLX07
3 mg/kg of HLX10 every two weeks infusion combined with 600 mg HLX07 weekly
|
| Experimental: HLX10 Plus HLX07 (Stage 1H) 3 mg/kg of HLX10 every two weeks infusion combined with 800 mg HLX07 weekly |
Drug: Experimental: Stage 1H: HLX10 Plus HLX07
3 mg/kg of HLX10 every two weeks infusion combined with 800 mg HLX07 weekly
|
Outcome Measures
Primary Outcome Measures
- Efficacy-ORR [at 16 weeks after first dose]
Objective Response Rate (ORR)
- Safety-adverse event profile [up to one year]
The proportion of patients suffered from drug related toxicities.
Secondary Outcome Measures
- Efficacy-Best ORR [up to one year]
Best response rate (Best ORR)
- Efficacy-PFS [up to one year]
Progression-free survival (PFS)
- Efficacy-OS [up to one year]
Overall survival (OS)
- The number of presence patients that develop of anti-durg antibody (immunogenicity). [up to one year]
- maximum concentration (Cmax) [up to one year]
- trough concentration (Ctrough) [up to one year]
- half-life (T1/2) [up to one year]
- clearance rate (CL) [up to one year]
- volume of distribution (Vss) [up to one year]
- area under concentration (AUC0-tau) [up to one year]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Eligible patients must be 18 years of age or older or per local regulation AND younger than 80 years old age.
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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.)
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Lesion must be measurable based on RECIST, version 1.1.
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Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 at the time of study entry.
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Able to provide informed consent.
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A life expectancy longer than three months.
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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.
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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.
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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.
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Adequate cardiac function defined as left ventricular ejection fraction (LVEF) ≥ 50% measured by multigated acquisition (MUGA) scan or cardiac ultrasound.
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Use of effective contraceptive measures if procreative potential exists .
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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.
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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:
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Patients who still have persistent ≥ grade 2 toxicities from prior therapies.
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Patients with primary nasopharynx cancers.
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Squamous cell carcinoma of unknown primary in cervical lymph node.
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Concurrent unstable or uncontrolled medical conditions. Either of the followings:
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Active systemic infections currently under treatment with antimicrobial agents;
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Poorly controlled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥100 mmHg), or poor compliance with anti-hypertensive agents;
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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;
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Uncontrolled diabetes or poor compliance with hypoglycemic agents;
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The presence of chronically unhealed wound or ulcers;
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Other chronic diseases, which, in the opinion of the investigator, could compromise safety of the patient or the integrity of study.
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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.
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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).
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Pregnancy (confirmed by serum beta human chorionic gonadotropin [ßHCG]) or breast-feeding.
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Known history of human immunodeficiency virus infection (HIV).
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Patient who has an active or a documented history of autoimmune disease.
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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).
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Patient who has a history of interstitial lung disease.
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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.
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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.
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Patients who previously have severe allergic reaction to anti-EGFR monoclonal antibody (CTCAE grade ≥3).
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Patients who have previously received immune check point therapy, including but not limit to anti-PD1 and anti-PDL1.
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The patient is the investigator, sub-investigator or any one directly involved in the conduct of the study.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Shanghai Henlius Biotech Inc. | Shanghai | Shanghai | China | 200233 |
Sponsors and Collaborators
- Shanghai Henlius Biotech
Investigators
- Principal Investigator: Ye Guo, PhD, Shanghai East Hospital
- Principal Investigator: Guochun Cao, Jiangsu Cancer Institute & Hospital
- Principal Investigator: Meiyu Fang, Cancer Hospital of The University of Chinese Academy of Sciences
- Principal Investigator: Guangyuan Hu, Tongji Hospital
- Principal Investigator: Xiaohui He, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
- Principal Investigator: Yan Sun, Peking University Cancer Hospital & Institute
- Principal Investigator: Wei Wang, Hunan Cancer Hospital
- Principal Investigator: Shubin Wang, Peking University Shenzhen Hospital
- Principal Investigator: Qingyuan Zhang, Harbin Medical University
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- HLX10HLX07-001