Clinical Trials /

Phase 1, First in Human, Open-Label, Dose-Escalation Study of 609A in China

NCT03998345

Description:

Phase 1, First in Human, Open-Label, Dose-Escalation Study of 609A in the Patients with Locally advanced/Metastatic Solid Tumors in China.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Phase 1, First in Human, Open-Label, Dose-Escalation Study of 609A in China
  • Official Title: A First-in-Human, Open-label, Phase 1 Dose-Escalation Study of 609A in Subjects With Locally Advanced/Metastatic Solid Tumors in China

Clinical Trial IDs

  • ORG STUDY ID: SSGJ-609-UND-I-01
  • NCT ID: NCT03998345

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
609A609A group

Purpose

Phase 1, First in Human, Open-Label, Dose-Escalation Study of 609A in the Patients with Locally advanced/Metastatic Solid Tumors in China.

Detailed Description

      This is a first-in-human (FIH), open-label, phase 1 dose-escalation study of 609A in China, a
      recombinant monoclonal anti-PD-1 antibody product, in subjects with Locally
      advanced/Metastatic Solid Tumors, who must have failed standard treatment (disease
      progression or intolerance) or lack of standard treatment. If there is a driver gene variant,
      the subjects must have failed the standard treatment for the driver gene, and there is no
      other standard treatment.
    

Trial Arms

NameTypeDescriptionInterventions
609A groupExperimentalDose escalation will be conducted using a traditional 3+3 design. Dose Escalation Level cohort 1. Dose 1 mg/kg, Q3W, IV. Subjects 3-6; Dose Escalation Level cohort 2. Dose 3 mg/kg, Q3W, IV. Subjects 3-6; Dose Escalation Level cohort 3. Dose 200mg, Q3W, IV. Subjects 3-6; Dose Escalation Level cohort 4. Dose 10 mg/kg, Q3W, IV. Subjects 3-6. If 10mg/kg cannot be tolerated, add a dose level of 400mg to assess the tolerance
  • 609A

Eligibility Criteria

        Inclusion Criteria:

        Subjects must meet all the following inclusion criteria to be eligible for participation in
        this study:

          -  Able to understand and willing to sign the Informed Consent Form(ICF).

          -  No limit gender .

          -  Age range: from 18 years to 70 years.

          -  Subjects with histologically or cytologically confirmed locally advanced-stage or
             metastatic tumor must have failed standard treatment (disease progression or
             intolerance) or lack of standard treatment. If there is a driver gene variant, the
             subjects must have failed the standard treatment for the driver gene, and there is no
             other standard treatment.

          -  Patients who had been previously treated for brain metastases, must have asymptomatic
             or radiographic/clinical stability and no need for steroid therapy of brain metastases
             to be enrolled in this study within 4 weeks prior to enrollment .

          -  According to RECIST1.1, Patients must have at least one measurable lesion (target or
             non-target).

          -  ECOG scores 0,1 or 2.

          -  Life expectancy ≥3 months

          -  Must have adequate organ function, prior to start of 609A, including the following:

               1. Bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.0 ×109/L; platelet
                  count≥ 100 × 109/L; hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L;

               2. Hepatic: total bilirubin ≤ 1.5 times the upper limit of normal (ULN), aspartate
                  transaminase (AST) and/or alanine aminotransferase (ALT) ≤ 3 × ULN (≤5 × ULN if
                  with liverinvolvement)

               3. Renal: serum creatinine ≤1.5 times the ULN or estimated creatinineclearance
                  ≥50mL/min (Cockroft and Gault formula).

               4. Coagulation tests INR≤ 2 (Exception: INR 2 to ≤ 3 is acceptable for subjects on
                  Warfarin anticoagulation), activated partial thromboplastin time (aPTT) ≤ 1.5 ×
                  ULN

          -  Female patient with fertility or male patient whose partner has fertility should use
             one or more contraceptive methods for contraception from the screening period to five
             half-lives after the last treatment. These measures include, but are not limited to,
             oral or implantable injections of hormonal contraceptives; intrauterine birth control
             ring or placement of intrauterine system (IUS) hormone-releasing intrauterine device;
             or use of barrier methods such as condoms or septum and spermicide products. Women of
             childbearing potential must have a negative pregnancy test ≤ 72 hours prior to the
             first dose of study drug. Postmenopausal women must have been amenorrhoeic for at
             least 12 months to be considered of non-childbearing potential.

        Exclusion Criteria:

        Subjects who meet any of the following criteria will not be enrolled:

          -  History of life-threatening hypersensitivity or known to be allergic to protein drugs
             or recombinant proteins or excipients in 609A drug formulation.

          -  Subjects who had experienced severe allergic reactions after administration of other
             monoclonal antibodies

          -  Pregnant or nursing females

          -  Regarding previous anti-tumor therapy:

               1. Subjects who have received any anticancer drugs approved or investigational,
                  including chemotherapy,hormonal therapy (Exceptions: hormone-replacement therapy,
                  testosterone or oral contraceptives), biologic therapy, have stopped treatment
                  for less than 3 weeks or 5 half-lives, whichever is longer, before first dose of
                  609A.

               2. Subjects who have stopped systemic radiation therapy less than 3 weeks before
                  first dose of 609A, or local radiotherapy or radiation therapy for bone
                  metastases less than 2 weeks before first dose of 609A. Therapeutic
                  radiopharmaceuticals were taken within 8 weeks before first dose of 609A.

               3. Subjects who have received prior immunotherapies targeting T cell stimulation
                  such as (e.g. anti-PD-1, anti- PD-L1 or anti-CTLA-4) ,have stopped treatment less
                  than 3 months before first dose of 609A.

               4. The ADA antibody of anti-PD-1 drug in plasma was positive during screening.

               5. Subjects who have received immunogonists (such as interleukin-2 gamma interferon,
                  oncolytic virus, mistletoe extract, etc.) or drugs known to interfere with major
                  organ function (e.g., hypericin) , have stopped treatment less than 4 weeks or 5
                  half-lives, whichever is longer, before first dose of 609A.

          -  Subjects with severe chronic or active infections requiring systemic antimicrobial,
             antifungal, or antiviral treatment, including tuberculosis.

          -  HIV infection

          -  Active hepatitis B or C. HBV carriers without active disease (HBV DNA titer< 1000
             cps/mL or 200 IU/mL) or cured Hepatitis C (negative HCV RNA test) may been rolled

          -  Subjects with history of interstitial lung disease or noncommunicable pneumonia, or
             uncontrolled pulmonary fibrosis or acute pulmonary disease . Local interstitial
             pneumonia due to radiotherapy was excluded.

          -  Acute or chronic uncontrolled renal disease( Exception: Renal carcinoma, metastatic
             renal cancer), pancreatitis or liver disease (per investigator assessment).

          -  Any remaining AEs > grade 1 from prior anti-tumor treatment as per CTCAE v5. 0, with
             exception of the residual hair loss.

          -  Any SAE occurred during previous pd-1 / pd-l1 treatment, including but not limited to
             interstitial pneumonia and myocarditis.

          -  Subjects who experienced immunotherapy-related adverse events (irAE) grade ≥ 3, or who
             had to discontinue prior anti-PD-1, anti-PD-L1, or CTL4 treatment due to irAEs of any
             grade

          -  Subjects with acute myocardial infarction, unstable angina pectoris, stroke, or
             transient ischemic attack occurred within 6 months prior to admission. Subjects with
             congestive heart failure rated as grade 2 or above (including grade 2) by the New York
             college of cardiology (NYHA) ,LVEF<50%.And subjects with the following heart diseases:

               1. ECG QTcF> 480 msec during screening.

               2. Right bundle branch block and left anterior half branch block or complete left
                  bundle branch block.

               3. Subjects with congenital long QT syndrome or a family history of unexpected
                  sudden cardiac death.

               4. Subjects with ventricular tachyarrhythmia or history of tachyarrhythmia.

               5. Bradycardia with obvious clinical significance (< 50 times/min).

               6. Subjects using pacemakers.

               7. Subjects with other heart disease with significant clinical significance.

          -  Sustained systolic blood pressure >160 mm Hg and/or diastolic blood pressure >100 mm
             Hg after antihypertensive medication.

          -  Fever and neutropenia occurred within 1 week before the first dose of 609A.

          -  Subjects who have had major surgery within 21 days before the first dose of 609A
             ((excluding diagnostic biopsies).

          -  Live attenuated vaccines were administered within 28 days before the first dose of
             609A.

          -  Patients who had received treatment with any herbal or alternative therapies or
             Chinese prepared medicine within 7 days before the first dose of 609A.

          -  History of primary immunodeficiency, stem cell or organ transplant, or previous
             clinical diagnosis of tuberculosis disease.

          -  Subjects with active autoimmune diseases or history of autoimmune diseases should be
             excluded; these include but are not limited to subjects with a history of immune
             related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy,
             Guillain- Barre syndrome, myasthenia gravis, systemic lupus erythematosus (SLE),
             connective tissue diseases, scleroderma, inflammatory bowel disease including Crohn's
             disease and ulcerative colitis, hepatitis, toxic epidermal necrolysis (TEN),
             Stevens-Johnson syndrome, or antiphospholipid syndrome.

          -  Subjects with condition requiring systemic treatment with either corticosteroids (>15
             mg/day prednisone or equivalent) or other immunosuppressive medications within 14 days
             before the planned first dose of study drug. Inhaled or topical steroids, and adrenal
             replacement steroid doses ≤ 10 mg daily prednisone equivalent are permitted in the
             absence of active autoimmune disease. Ophthalmologic, nasal and intra-articular
             injections of steroids are acceptable.

          -  Any other serious underlying medical (e.g. uncontrolled diabetes mellitus, active
             uncontrolled infection, active gastric ulcer, uncontrolled seizures, cerebrovascular
             incidents, gastrointestinal bleeding, severe signs and symptoms of clotting
             disorders), psychiatric, psychological, familial or geographical condition that, in
             the judgment of the investigator, may interfere with the planned staging, treatment
             and follow-up, affect subject compliance or place the subject at high risk from
             treatment-related complications.

          -  Any other conditions not suitable for subjects to be enrolled in this study, as
             determined by the investigator.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Treatment-Emergent Adverse Events
Time Frame:for 90 days
Safety Issue:
Description:To access adverse events (AEs) per the NCI CTCAE 5.0.

Secondary Outcome Measures

Measure:AUC
Time Frame:for 90 days
Safety Issue:
Description:Area Under the Curve of 609A
Measure:Cmax
Time Frame:for 90 days
Safety Issue:
Description:Maximum Plasma Concentration of 609A
Measure:t1/2
Time Frame:for 90 days
Safety Issue:
Description:Half life of 609A in blood
Measure:CL
Time Frame:for 90 days
Safety Issue:
Description:Plasma clearance of 609A
Measure:ORR
Time Frame:for 1 year
Safety Issue:
Description:the rate of completely response [CR] and partial response [PR] patients
Measure:DCR
Time Frame:for 1 year
Safety Issue:
Description:disease control rates of the patients with 609A
Measure:DOR
Time Frame:for 1 year
Safety Issue:
Description:Duration of response of the patients with 609A
Measure:PFS
Time Frame:for 1 year
Safety Issue:
Description:Progression-free survival of the patients with 609A
Measure:OS
Time Frame:for 1 year
Safety Issue:
Description:overall survival of the patients with 609A
Measure:ADA
Time Frame:for 1 year
Safety Issue:
Description:to detect the presence of anti-609A antibody
Measure:PD-L1
Time Frame:for 1 year
Safety Issue:
Description:to evaluate the expression of pd-l1

Details

Phase:N/A
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd.

Last Updated

September 5, 2020