Clinical Trials /

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

NCT03950297

Description:

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

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: SSGJ-609-UND-US-I-01
  • NCT ID: NCT03950297

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

Detailed Description

      This is a first-in-human (FIH), open-label, phase 1 dose-escalation study of 609A, a
      recombinant monoclonal anti-PD-1 antibody product, in subjects with Locally
      advanced/Metastatic Solid Tumors, who must have received, or be intolerant to all available
      approved or standard therapies known to confirm clinical benefit, or for whom no standard
      therapy exits.
    

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;
  • 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).

          -  Male or female ≥ 18years.

          -  Subjects with histologically or cytologically confirmed advanced-stage or metastatic
             tumor must have received, or be intolerant to all available approved or standard
             therapies known to confirmed clinical benefit, or for whom standard therapy does not
             exist.

          -  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
                  [http://www.mdcalc.com/creatinine-clearance-cockcroft-gault-equation/]).

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

          -  Regarding prior anti-tumortherapy:

               1. Subjects who have received any anticancer drugs approved or investigational,
                  including chemotherapy, immune therapy, hormonal therapy (Exceptions:
                  hormone-replacement therapy, testosterone or oral contraceptives), biologic
                  therapy, must have stopped treatment at least 3 weeks, or five half-lives,
                  whichever is shorter, before first dose of 609A.

               2. Generalized radiation therapy must have stopped 3 weeks before first dose of
                  609A, or local radiotherapy or radiation therapy for bone metastases must have
                  stopped 2 weeks before first dose of 609A. No therapeutic radiopharmaceuticals
                  are 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) must have stopped treatment
                  for at least 4 weeks before first dose of 609A.

          -  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.

          -  According to RECIST1.1, the subject should have an assessable lesion (target lesion or
             non- target lesion)

          -  According to RECIST1.1, the subject should have an assessable lesion (target lesion or
             non- target lesion) ECOG score 0, 1 or 2 point.

        Exclusion Criteria:

          -  Subjects who meet any of the following criteria cannot be enrolled: Life expectancy <
             3 months.

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

          -  Any remaining AEs > grade 1 from prior anti-tumor treatment as per CTCAE v5. 0, with
             exception of the residual hair loss; Any involvement of CNS excluded except: Based on
             screening brain magnetic resonance imaging (MRI), patients must have one of the
             following:

               1. No evidence of brain metastases or has to be clinically stable for at least 4
                  weeks

               2. Untreated brain metastases not needing immediate localtherapy

          -  Pregnant or nursing females

          -  Subjects who have had major surgery within the 21-days from the screening;

          -  Subjects with history of interstitial lung disease or idiopathic pulmonary fibrosis or
             unresolved active or chronic inflammatory pulmonary disease are excluded. Subjects
             with a history of radiation pneumonitis which has resolved areeligible.

          -  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.

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

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

          -  Acute or chronic uncontrolled renal disease, pancreatitis or liver disease (per
             investigator assessment).

          -  Subjects with any type of primary immunodeficiencies will be excluded from thestudy.

          -  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 activeautoimmune disease. Ophthalmologic, nasal and intra-articular
             injections of steroids areacceptable.

          -  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.

          -  Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure
             NYHA III or IV, unstable angina pectoris even if medically controlled, history of
             myocardial infarction during the last 6 months, ECG QTcB (Bazetts) > 450msec, serious
             arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal
             supraventriculartachycardia).

          -  Hypertension (defined as sustained systolic blood pressure> 160 mm Hg and / or post-
             diastolic blood pressure with antihypertensive drugs> 100 mmHg;

          -  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.

          -  Has received a live and attenuated vaccine within 28 days prior to the first dose of
             study drug.

          -  Patients who had received treatment with any herbal or alternative therapies or
             Chinese prepared medicine within 7 days prior to the first dose of the studydrug.

          -  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 antiphospholipidsyndrome.
      
Maximum Eligible Age:N/A
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 monitor 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:
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:PFS
Time Frame:for 1 Year
Safety Issue:
Description:Progression-free survival of the patients with 609A
Measure:DOR
Time Frame:for 1 Year
Safety Issue:
Description:Duration of response of the patients with 609A
Measure:OS
Time Frame:for 1 Year
Safety Issue:
Description:overall survival of the patients with 609A
Measure:Immunogenicity
Time Frame:for 1 Year
Safety Issue:
Description:the presence of anti-609A antibody will be assessed

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd.

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