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
- 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
- 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
- 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:
ANC≥1.5 x 109/L; Hemoglobin≥9 g/dL; Platelets≥100 x 109/L
Calculated creatinine clearance≥60 mL/min (Cockcroft-Gault method)
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.
- 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
- 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
- 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
- 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
- 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.