Clinical Trials /

Evaluate the Efficacy and Safety of HLX10 in Combination With HLX07 in Patients With Advanced Head and Neck Tumors

NCT04297995

Description:

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

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Evaluate the Efficacy and Safety of HLX10 in Combination With HLX07 in Patients With Advanced Head and Neck Tumors
  • Official Title: Evaluate the Efficacy and Safety of HLX10, PD-1 mAb, in Combination With HLX07, EGFR mAb, in Patients With Advanced Head And Neck Tumors

Clinical Trial IDs

  • ORG STUDY ID: HLX10HLX07-001
  • NCT ID: NCT04297995

Conditions

  • Head and Neck Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
Experimental: Stage 1L: HLX10 Plus HLX07HLX10 Plus HLX07 (stage 1L)
Experimental: Stage 1H: HLX10 Plus HLX07HLX10 Plus HLX07 (Stage 1H)

Purpose

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

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.
    

Trial Arms

NameTypeDescriptionInterventions
HLX10 Plus HLX07 (stage 1L)Experimental3 mg/kg of HLX10 every two weeks infusion combined with 600 mg HLX07 weekly
  • Experimental: Stage 1L: HLX10 Plus HLX07
HLX10 Plus HLX07 (Stage 1H)Experimental3 mg/kg of HLX10 every two weeks infusion combined with 800 mg HLX07 weekly
  • Experimental: Stage 1H: HLX10 Plus HLX07

Eligibility Criteria

        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.
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Efficacy-ORR
Time Frame:at 16 weeks after first dose
Safety Issue:
Description:Objective Response Rate (ORR)

Secondary Outcome Measures

Measure:Efficacy-Best ORR
Time Frame:up to one year
Safety Issue:
Description:Best response rate (Best ORR)
Measure:Efficacy-PFS
Time Frame:up to one year
Safety Issue:
Description:Progression-free survival (PFS)
Measure:Efficacy-OS
Time Frame:up to one year
Safety Issue:
Description:Overall survival (OS)
Measure:The number of presence patients that develop of anti-durg antibody (immunogenicity).
Time Frame:up to one year
Safety Issue:
Description:
Measure:maximum concentration (Cmax)
Time Frame:up to one year
Safety Issue:
Description:
Measure:trough concentration (Ctrough)
Time Frame:up to one year
Safety Issue:
Description:
Measure:half-life (T1/2)
Time Frame:up to one year
Safety Issue:
Description:
Measure:clearance rate (CL)
Time Frame:up to one year
Safety Issue:
Description:
Measure:volume of distribution (Vss)
Time Frame:up to one year
Safety Issue:
Description:
Measure:area under concentration (AUC0-tau)
Time Frame:up to one year
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Shanghai Henlius Biotech

Last Updated

March 5, 2020