| Eligibility |
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 no standard anti-cancer therapy option, who
failed established standard medical anti-cancer therapies for a given tumor type.
- Subject is male or female and = 18 years of age on the day of signing informed
consent. However, in case a subject is younger than 20 years old, written informed
consent will be obtained from both a subject and a legal representative.
- Subject must have a performance status of 0 to 1 on the Eastern Cooperative Oncology
Group (ECOG) Performance Scale.
- Subject must have adequate hematologic and organ function.
- Subject has voluntarily agreed to participate by giving written informed consent.
- Women able to get pregnant 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 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
Informed Consent through 120 days after the last dose of study therapy. Women who have
had a surgical hysterectomy and/or bilateral oophorectomy, or who are postmenopausal
and have not had a menstrual cycle for 12 consecutive months without medical/medicinal
reasons are not considered to be of childbearing potential. Approved contraceptive
methods include for example; intra uterine device, diaphragm with spermicide*,
cervical cap* with spermicide*, male condoms, or female condom *with spermicide* and
hormonal method of contraception. Spermicides alone are not an acceptable method of
contraception. *: not approved/certified in Japan.
Male subjects must agree to use an adequate method of contraception starting with Informed
Consent 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 or 28 days whichever is shorter 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. Grade 2
alopecia is allowed to enter.
- 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. 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 anti-PD-L1 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 of hydrocortisone (or 5 mg of prednisone) in the
morning and 10 mg of hydrocortisone (or 2.5 mg of prednisone) in the evening. Topical,
intraocular, and intranasal steroids are allowed.
- 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.
- 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 irrespective of
causes (For the purpose of screening of interstitial lung disease, chest X-ray,
Sialylated carbohydrate antigen (KL-6) (hereafter, KL-6), percutaneous arterial blood
oxygen saturation (hereafter, SpO2) and auscultation are conducted).
- 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 (Fridericia's formula) interval
(e.g., repeated demonstration of a QTc interval >450 milliseconds (ms) as a guidance
considering the patient's background of physiological conditions), 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. However, breastfeeding female subject who
stopped breastfeeding can be included only if she agrees to stop breastfeeding during
the treatment of the investigational drug and to restart breastfeeding 120 days after
the last dose of the investigational drug.
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