Clinical Trials /

A Study of KN046 in Patients With Thymic Carcinoma Who Failed Immune Checkpoint Inhibitors

NCT04925947

Description:

This study will assess the safety and efficacy of the study drug KN046 in patients with advanced thymic carcinoma who progressed after prior treatment with immune checkpoint inhibitor therapy.

Related Conditions:
  • Thymic Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of KN046 in Patients With Thymic Carcinoma Who Failed Immune Checkpoint Inhibitors
  • Official Title: Phase II Study of KN046 in Patients With Thymic Carcinoma Who Failed Immune Checkpoint Inhibitors

Clinical Trial IDs

  • ORG STUDY ID: 20-08022493
  • NCT ID: NCT04925947

Conditions

  • Thymic Carcinoma

Interventions

DrugSynonymsArms
KN046KN046

Purpose

This study will assess the safety and efficacy of the study drug KN046 in patients with advanced thymic carcinoma who progressed after prior treatment with immune checkpoint inhibitor therapy.

Detailed Description

      Patients will receive KN046 intravenously at 5 mg/kg every 2 weeks until progression or
      excessive toxicity for up to to two years, with the goal of this trial to contribute to the
      development of active and well tolerated treatments for patients who have progressed on prior
      treatment therapies.

      Recently, molecules that combine PD-1 and CTLA-4 have been developed for patients with lung
      cancer, with the hope that targeted therapy will be more effective than standard of care
      therapies. KN046 is believed to be less toxic than other targeted therapies with an
      assumption that the whole molecule can actively target tumor tissue for a much higher
      affinity of the anti-PD-L1 portion and a weaker affinity for anti-CTLA-4, leading to less
      autoimmune disorders and toxicities for patients than seen with other targeted therapies.
    

Trial Arms

NameTypeDescriptionInterventions
KN046ExperimentalKN046 will be given intravenously every 2 weeks.
  • KN046

Eligibility Criteria

        Inclusion Criteria:

          -  Signed informed consent form.

          -  Male or female, 18 years of age or older; willing and able to complete all required
             procedures of study.

          -  Pathologically confirmed diagnosis of thymic carcinoma; a tumor sample is required for
             confirmation of pathological diagnosis and further studies on the tumor tissue.

          -  Inoperable or metastatic disease.

          -  Progressive disease documented in the last 6 months.

          -  Has failed platinum-based chemotherapy, with progression either during or after
             treatment.

          -  Had failed at least one regimen of systemic therapy containing immune checkpoint
             blockade therapy targeting PD-1, PD-L1, or CTLA-4 for locally advanced unresectable or
             metastatic disease. Subjects should have documented progressive disease while or after
             an immune checkpoint therapy. If subjects discontinued therapy due to reasons other
             than progressive disease, subjects should have completed at least 2 cycles of immune
             checkpoint therapy.

          -  Baseline measurable disease according to RECIST 1.1. Target lesions situated in a
             previously irradiated area are considered measurable if progression has been
             demonstrated in such lesions.

          -  ECOG performance status of 0 or 1.

          -  Adequate organ function assessed within 7 days prior to first trial treatment:

        Hematological function:

        ANC≥1.5 x 109/L; Hemoglobin≥9 g/dL; Platelets≥100 x 109/L

        Renal function:

        Calculated creatinine clearance≥60 mL/min (Cockcroft-Gault method)

        Hepatic function:

        Total bilirubin≤1.5 x ULN (or 2.5 x ULN for documented Gilberts' syndrome); ALT/AST≤3.0 x
        ULN (or 5.0 x ULN for documented liver metastasis); INR or aPTT ≤1.5 x ULN

          -  Have a life expectancy of at least 3 months.

          -  If female of childbearing potential, have a negative serum pregnancy test within 7
             days prior to first trial treatment.

          -  If female of childbearing potential or a male subject with a partner with childbearing
             potential, be willing to use a highly effective method of contraception (with a
             failure rate of less than 1.0% per year) from first study treatment to 24 weeks after
             completion of the trial treatment.

        Exclusion Criteria:

          -  Thymomas, thymolipoma, germ cell tumors, teratomas, seminomas.

          -  Leptomeningeal metastasis or untreated active CNS metastasis or leptomeningeal
             metastasis. Subjects with CNS metastasis may be eligible provided they are treated and
             clinically stable for at least 4 weeks and have no evidence of new or enlarging brain
             metastases and also are off steroids 7 days prior to first trial treatment.

          -  Is currently participating and receiving an investigational drug or has participated
             in a study of an investigational drug within 4 weeks or within 5 times of half-life
             (no less than 2 weeks), whichever is shorter, prior to the first dose of trial
             treatment.

          -  Major surgery for any reason, except diagnostic biopsy, within 4 weeks of the first
             administration of trial treatment and/or if the subject has not fully recovered from
             the surgery within 4 weeks of the first administration of trial treatment.

          -  Radiation within 4 weeks prior to the first administration of trial treatment;
             palliative radiation will be allowed if more than 2 weeks before start of KN046
             treatment.

          -  Subjects receiving immunosuppressive agents (such as systemic steroids); topical use
             of steroids and steroid inhalers are allowed. Replacement therapy because of adrenal
             insufficiency is also allowed.

          -  Vaccination within 28 days of the first administration of trial treatment, except for
             administration of inactivated vaccines (e.g., inactivated influenza vaccines).

          -  Has interstitial lung disease, or a history of pneumonitis that required oral or
             intravenous glucocorticoids to assist with management.

          -  History or current active autoimmune disease that might deteriorate when receiving an
             immunostimulatory agent, including but not limited to:

        Myasthenia gravis (MG), Good syndromes, ISAACS syndromes, polymyositis, myocarditis,
        neuromuscular syndrome (myotonic dystrophy myositis, Eaton-Lambert syndrome), blood
        disorders (red cell aplasia, hypogammaglobulinemia, T-cell deficiency syndrome,
        erythrocytosis, pancytopenia, megakaryocytopenia, T-cell lymphocytosis, pernicious anemia),
        systemic lupus erythematosus, sarcoidosis, scleroderma, Crohn's disease, inflammatory bowel
        disease, Wegener syndrome (granulomatosis with polyangitis, Grave's disease, rheumatoid
        arthritis, hypophysitis, uveitis), autoimmune hepatitis, systemic sclerosis (for example
        scleroderma), Hashimoto thyroiditis (with the exception as stated below),
        hyperparathyroidism, stiff-person syndrome, Addison disease, panhypopituitarism, autoimmune
        vasculitis, autoimmune neuropathy (Guillain-Barre syndrome) etc.

        NOTE: Subjects with Type I diabetes, vitiligo, psoriasis, hypo- or hyperthyroid disease,
        Sjögren syndrome not requiring immunosuppressive treatment are eligible. Subjects requiring
        hormone replacement with corticosteroids are eligible if the steroids are administered only
        for the purpose of hormonal replacement and at doses ≤10 mg or equivalent prednisone per
        day. Administration of steroids for other conditions through a route known to result in a
        minimal systemic exposure (topical, intranasal, intra-ocular, or inhalation) are
        acceptable.

          -  Previous malignant disease other than the target malignancy to be investigated in this
             study with the exception of adequately treated non-melanomatous cancers of the skin,
             in situ carcinoma of the prostate/cervical/breast cancer, or other malignancy treated
             at least 5 years previously with surgery and/or curative radiotherapy, and there is no
             evidence of recurrence since that time.

          -  History of uncontrolled intercurrent illness including but not limited to: Active HBV
             or HCV infection (If HBsAg and HCV antibody positive, HBV DNA and HCV RNA assay should
             be performed. Subjects may be eligible if HBV DNA ≤ 500 UI/ml (or 2000 copies/ml) or
             HCV RNA negative); Known HIV infection or known history of acquired immune deficiency
             syndrome (AIDS); Active tuberculosis infection; Active infection within 2 weeks prior
             to the first dose of trial treatment that require the use of systemic antibiotics;
             Hypertension uncontrolled by standard therapies (not stabilized to 150/90 mmHg);
             Clinically significant (that is, active) cardiovascular disease: cerebral vascular
             accident/stroke (< 6 months prior to enrolment), myocardial infarction (< 6 months
             prior to enrolment), unstable angina pectoris, congestive heart failure (New York
             Heart Association Classification Class II-IV) or serious cardiac arrhythmia requiring
             medication (including corrected QT interval prolongation of > 470 msec calculated
             according to Fridericia and/or pacemaker or prior diagnosis of congenital long QT
             syndrome

          -  Persisting toxicity related to prior therapy (including any prior investigational
             therapy) of CTCAE ≥ grade 2 (NCI-CTCAE v5.0) or related toxicity not recovery to
             baseline, with the exception of alopecia of any grade.

          -  Prior allo-HSCT or solid organ transplant.

          -  Known severe hypersensitivity reactions to antibody drug (≥ grade 3 NCI-CTCAE v5.0),
             any history of anaphylaxis, uncontrolled asthma (that is, 3 or more features of
             partially controlled asthma), or any history of severe drug hypersensitivity (for
             example immune mediated liver toxicity, immune mediated thrombocytopenia or anemia).

          -  Is pregnant or breastfeeding.

          -  Other medical conditions that at the discretion of investigator interfere with the
             requirements of the trial in terms of safety or efficacy evaluation, or treatment
             compliance. These include but are not limited to psychiatric or substance abuse
             disorder, moderate to large pleural fluid/cardiac effusion/ascites, or
             recurrent/refractory pleural fluid/cardiac effusion/ascites.

          -  .Subjects with history or baseline positive antiacetylcholine receptor (AChR)
             autoantibody and anti-MuSK autoantibody.

          -  Subjects who developed grade 3 or above immune related AE which could not be managed
             by steroid or immune suppressant will be excluded.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Anti-tumor activity of KN046 in subjects with thymic carcinoma, determined by subject disease response rate defined by the RECIST 1.1 criteria.
Time Frame:Through study completion (an average of 2 years)
Safety Issue:
Description:Disease response rate

Secondary Outcome Measures

Measure:Safety of KN046 in subjects with thymic carcinoma, measured by the number of adverse events that occur in subjects while receiving study treatment.
Time Frame:Through study completion (an average of 2 years)
Safety Issue:
Description:
Measure:Tolerability of KN046 in subjects with thymic carcinoma, measured by the severity of adverse events that occur in subjects while receiving study treatment, assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time Frame:Through study completion (an average of 2 years)
Safety Issue:
Description:
Measure:Duration of response for KN046 in subjects with thymic carcinoma, determined by subject disease response rate defined by the RECIST 1.1 criteria.
Time Frame:From first documented response (PR or CR) to the date of first documented disease progression or death due to underlying cancer (an average of 2 years)
Safety Issue:
Description:
Measure:Progression Free Survival (PFS) for KN046 in subjects with thymic carcinoma, determined by subject disease response rate defined by the RECIST 1.1 criteria.
Time Frame:From start of treatment to time of progression (an average of 2 years)
Safety Issue:
Description:
Measure:Overall Survival (OS) for KN046 in subjects with thymic carcinoma, determined by subject disease response rate defined by the RECIST 1.1 criteria.
Time Frame:From baseline to death due to underlying cancer (on average 30 months)
Safety Issue:
Description:In previous studies, OS has not been reached. However OS rates for 6 and 9 months were 74.3% and 65.2%, respectively.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Weill Medical College of Cornell University

Last Updated

June 29, 2021