Clinical Trials /

Phase 1 Study of Anti-PD-L1 Monoclonal Antibody KN035 to Treat Locally Advanced or Metastatic Solid Tumors

NCT02827968

Description:

This is an open label, dose escalation study to evaluate the safety and tolerability of KN035 in advanced and metastatic solid tumor.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase 1 Study of Anti-PD-L1 Monoclonal Antibody KN035 to Treat Locally Advanced or Metastatic Solid Tumors
  • Official Title: A Phase I, Open Label, Dose Escalation Study of The Safety and Pharmacokinetics of Anti-PD-L1 Monoclonal Antibody KN035 Administered in Subcutaneous Injection as A Single Agent to Subjects With Locally Advanced or Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: KN035-US-001
  • NCT ID: NCT02827968

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
KN035KN035

Purpose

This is an open label, dose escalation study to evaluate the safety and tolerability of KN035 in advanced and metastatic solid tumor.

Detailed Description

      The dose escalation will follow the traditional 3+3 design. Cohorts of 3-6 subjects will be
      enrolled sequentially at escalating doses of 1, 2.5, 5 and 10 mg/kg weekly. Dosing schedule
      for cohorts 2 and above may change after interim PK analysis after Cohort 1 Cycle 1 to
      bi-weekly or other regimen based on elimination profile of KN035 to avoid excessive drug
      accumulation. Dose escalation will continue until identification of MTD, up to a maximum
      dose of 10 mg/kg. MTD is defined as the highest dose studied at which no more than 1 of 6
      subjects has experienced a dose-limiting toxicity (DLT) in Cycle 1.
    

Trial Arms

NameTypeDescriptionInterventions
KN035ExperimentalCohorts of 3-6 subjects will be enrolled sequentially at escalating doses of 1, 2.5, 5 and 10 mg/kg weekly.
  • KN035

Eligibility Criteria

        Inclusion Criteria:

          -  Subjects must have a histological or cytological diagnosis of any type of carcinoma,
             progressive metastatic disease, or progressive locally advanced disease not amenable
             to local therapy. Subjects must have failed established standard medical anti-cancer
             therapies for a given tumor type or have been intolerant to such therapy, or in the
             opinion of the Investigator have been considered ineligible for a particular form of
             standard therapy on medical grounds.

          -  Subject is male or female and ≥ 18 years of age on day of signing informed consent.

          -  Subject must have a performance status of 0 or 1 on the Eastern Cooperative Oncology
             Group (ECOG) Performance Scale.

          -  Subject must have adequate hematologic and organ function. Note: If subject is
             receiving anticoagulants, then value must be within therapeutic range for the
             condition the subject is being treated for.

          -  Subject has voluntarily agreed to participate by giving written informed consent. If
             subject has agreed to a newly obtained biopsy of tumor (that can be biopsied based on
             Investigator's assessment). Tissue obtained for the biopsy must not be previously
             irradiated. No systemic antineoplastic therapy may be received by the subject between
             the time of the biopsy and the first administration of KN035.

          -  Female subject of childbearing potential has a negative urine or serum pregnancy
             test. If the urine test is positive or cannot be confirmed as negative, a serum
             pregnancy test will be required. The serum pregnancy test must be negative for the
             subject to be eligible.

          -  Female subjects enrolled in the study, who are not free from menses for > 2 years,
             post hysterectomy/oophorectomy, or surgically sterilized, must be willing to use
             either 2 adequate barrier methods or a barrier method plus a hormonal method of
             contraception to prevent pregnancy or to abstain from heterosexual activity
             throughout the study, starting with Visit 1 through 120 days after the last dose of
             study therapy. Approved contraceptive methods include for example; intra uterine
             device, diaphragm with spermicide, cervical cap with spermicide, male condoms, or
             female condom with spermicide. Spermicides alone are not an acceptable method of
             contraception.

        Male subjects must agree to use an adequate method of contraception starting with the
        first dose of study drug through 120 days after the last dose of study therapy.

        Exclusion Criteria:

          -  Subject who not recovered from the effects of any prior chemotherapy, radioactive, or
             biological cancer therapy prior to the first dose of study therapy (for prior cancer
             therapy drugs, a washout of 5 half-lives is required), or who has not recovered to
             CTCAE Grade 1 or better from the adverse events due to cancer therapeutics
             administered more than 4 weeks earlier. Subject who has had erlotinib, gefitinib,
             afatinib, or crizotinib within 1 week prior to the first dose of study therapy, or
             who has not recovered to CTCAE Grade 1 or better from the adverse events due to any
             of these drugs administered more than 1 week earlier.

          -  Subject is expected to require any other form of antineoplastic therapy while on
             study (including maintenance therapy with another agent for NSCLC).

          -  Subject had prior treatment targeting PD-L1 axis or CTLA 4. Subjects with prior
             treatment targeting PD-1 are allowed to enroll if the subject has a washout time of
             at least 4 weeks. Examples of such agents include (but are not limited to):
             BMS-936559 (MDX 1105); MPDL3280A (RG7446); and MEDI4736.

          -  Subject has a medical condition that requires chronic systemic steroid therapy or
             requires any other form of immunosuppressive medication. However, subjects using
             physiologic replacement doses of hydrocortisone, or its equivalent, will be
             considered eligible for this study: up to 20 mg hydrocortisone (or 5 mg of
             prednisone) in the morning and 10 mg hydrocortisone (or 2.5 mg of prednisone) in the
             evening.

          -  Subject has risk factors for bowel obstruction or bowel perforation (examples include
             but not limited to a history of acute diverticulitis, intra-abdominal abscess, or
             abdominal carcinomatosis).

          -  Subject has a known history of a hematologic malignancy, malignant primary brain
             tumor or malignant sarcoma, or of another malignant primary solid tumor, unless the
             subject has undergone potentially curative therapy with no evidence of that disease
             for 5 years.

        Note: The time requirement does not apply to subjects who underwent successful definitive
        resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell
        carcinoma of the skin, in situ cervical cancer, or other in situ cancers.

          -  Subject has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Subjects with previously treated brain metastases may participate
             provided they are clinically stable for at least 4 weeks prior to study entry, have
             no evidence of new or enlarging brain metastases and are off steroids for at least 7
             days from first dose of KN035.

          -  Subject previously had a severe hypersensitivity reaction to treatment with another
             mAb.

          -  Subject has a history of pneumonitis or interstitial lung disease.

          -  Subject has an active autoimmune disease or a documented history of autoimmune
             disease or syndrome that requires systemic steroids or immunosuppressive agents.
             Subjects with vitiligo or resolved childhood asthma/atopy would be exception to this
             rule. Subjects that require intermittent use of bronchodilators or local steroid
             injections would not be excluded from the study. Subjects with hypothyroidism that is
             stable on hormone replacement will not be excluded from the study.

          -  Subject has an active infection requiring therapy.

          -  Subject is positive for Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies),
             active hepatitis B (HBsAg reactive) or hepatitis C (HCV RNA (qualitative) is
             detected); subjects with negative hepatitis C antibody testing may not need RNA
             testing.

          -  Subject has a history or current evidence of any condition, therapy, or laboratory
             abnormality that might confound the results of the study, interfere with the
             subject's participation for the full duration of the study, or is not in the best
             interest of the subject to participate, in the opinion of the treating Investigator.

          -  Subject has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  Subject has a marked baseline prolongation of QT/QTc interval (e.g., repeated
             demonstration of a QTc interval >450 milliseconds (ms)), or a history of additional
             risk factors for torsade de pointes (TdP, e.g., heart failure, hypokalemia, family
             history of Long QT Syndrome), or is using concomitant medications that prolong the
             QT/QTc interval.

          -  Subject is, at the time of signing informed consent, a regular user (including
             "recreational use") of any illicit drugs or had a recent history (within the last
             year) of substance abuse (including alcohol).

          -  Subjects with symptomatic ascites or pleural effusion. A subject who is clinically
             stable following treatment for these conditions (including therapeutic thoraco- or
             paracentesis) is eligible.

          -  Subject is pregnant or breastfeeding, or expecting to conceive or father children
             within the projected duration of the study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose limiting toxicities (DLTs)
Time Frame:From screening to up to cycle 1 (28 days)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Serum Concentrations of KN035
Time Frame:From Pre-dose of the first dose to up to 3 months after the last dose of study drug (up to approximately 2 years)
Safety Issue:
Description:Blood samples will be collected at Pre-dose, 6hrs,24 hrs,48hrs,96hrs after the end of the first injection of KN035, after injection of KN035 at Day 8, 15, 22 in first cycle and pre-dose and within 24hrs of following cycles(Cycle length = 28 days), and at the mandatory Safety Follow-up visits
Measure:Percentage of Participants with Best Overall Response as determined by Response Evaluation Criteria in Solid Tumours (RECIST) Version (v) 1.1
Time Frame:Baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination by the Sponsor, whichever occurs first (up to approximately 2 years)
Safety Issue:
Description:
Measure:Percentage of Participants with Objective Response as determined by RECIST v1.1
Time Frame:Baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination by the Sponsor, whichever occurs first (up to approximately 2 years)
Safety Issue:
Description:
Measure:Duration of Objective Response as determined by RECIST v1.1
Time Frame:Baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination by the Sponsor, whichever occurs first (up to approximately 2 years)
Safety Issue:
Description:
Measure:Progression Free Survival Duration as determined by RECIST v1.1
Time Frame:Baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination by the Sponsor, whichever occurs first (up to approximately 2 years)
Safety Issue:
Description:
Measure:Overall Survival Duration
Time Frame:Baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination by the Sponsor, whichever occurs first (up to approximately 2 years)
Safety Issue:
Description:
Measure:Percentage of participants with anti-therapeutic antibody (ATA)
Time Frame:From screening to up to 3 months after the last dose of study drug (up to approximately 2 years)
Safety Issue:
Description:Blood samples will be collected at Pre-dose of Cycle 1 and D1,8 of the following cycles.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:3D Medicines (Sichuan) Co., Ltd.

Trial Keywords

  • PDL-1

Last Updated

March 27, 2017