| Eligibility |
Inclusion Criteria:
1. Age =18 years;
2. Histologically or cytology-confirmed HER2-positive locally advanced, recurrent, or
metastatic gastric cancer (including adenocarcinoma of the gastro-esophageal
junction); HER2 positive is defined as IHC 3+, or IHC 2+ with ISH test positive
(HER2/CEP17 ratio = 2.0, or mean HER2 copy number = 6.0 signals/cell);
3. Failure of at least first-line standard therapy (trastuzumab plus chemotherapy); Note:
Neoadjuvant/adjuvant therapy previously administered with a trastuzumab-containing
regimen can be considered first-line therapy if the subject has progressed disease
during neoadjuvant/adjuvant therapy or within 6 months of completion of treatment;
4. Stage 1 : At least one measurable lesion at baseline according to RECIST 1.1; Stage 2:
At least one evaluable lesion at baseline according to RECIST 1.1; the area must not
have received previous radiotherapy, or there must be evidence of significant
progression after the end of radiotherapy;
5. ECOG Performance Status of 0 to 1.
6. Life expectancy = 3 months.
7. 7. The function of major organs must meet the following criteria : Hemoglobin (Hb) =
90 g/L; Absolute neutrophil (ANC) = 1.5×10^9/L; Platelet (PLT) = 90×10^9/L; (No whole
blood or component blood transfusion in the last 14 days; no pro-hematopoietic
cytokines used in the last 7 days); AST, ALT =2.5× ULN (upper limit of normal value)
(if liver metastases, AST, ALT =5×ULN); Total bilirubin (TBIL) =1.5×ULN; Albumin= 28
g/L; creatinine clearance = 50 mL/min (standard Cockcroft-Gault formula applied);
Activated partial thromboplastin time (APTT) = 1.5×ULN, international normalized ratio
(INR)/or prothrombin time (PT) = 1.5×ULN; (It is allowed to receive anticoagulants at
low stable doses, eg at a dose of aspirin 100 mg/day);
8. Left ventricular ejection fraction (LVEF) = 50% or lower limit of normal (LLN) in
local sites, measured by echocardiography (ECHO), cardiac radionuclide scanning (MUGA)
only in the absence of ECHO, with consistency at baseline and follow-up measurements;
9. Subjects agreed to use effective contraception during the study and for 6 months after
the last dose (women of childbearing age must confirm a negative serum pregnancy test
within 7 days prior to enrollment);
10. Female and male patient of childbearing age must agree to take adequate contraceptive
measures during the entire study period and through at least 6 months after the last
dose of study drug. (Women of childbearing age must have a negative pregnancy test
prior to study entry.)
11. Subjects are able and willing to comply with the study protocol.
Exclusion Criteria:
1. Subjects with untreated active brain metastases; Subjects will be admitted if their
brain metastases have been treated and the metastases are stable (brain imaging at
least 4 weeks prior to the first dose showed stable lesions with no new CNS symptoms,
or CNS symptoms have returned to baseline and no hormonal therapy is required at least
14 days prior to the first dose of the investigational treatment), and there is no
evidence of new or enlarged original brain metastases;
2. Other investigational medications received within 4 weeks prior to the first study
treatment, based on the time of the last trial dose;
3. Antineoplastic therapy such as chemotherapy, small molecule inhibitors, immunotherapy
(such as interleukin, interferon, or thymosin) within 4 weeks or 5 half-lives
(whichever is shorter but at least 2 weeks) prior to the first study treatment; Have
received Chinese herbal treatment with antitumor activity within 14 days before
administration;
4. Subjects recieved major surgery (e.g., transabdominal, transthoracic, etc.) within 28
days prior to the first study treatment; does not include minor procedures such as
diagnostic puncture or infusion device implantation), or major surgery is expected to
be required during the study;
5. Previous cumulative doses of doxorubicin exceeding 320 mg/m^2, or equivalent
conversion of other anthracyclines (anthracycline equivalent: 1 mg doxorubicin = 2 mg
epirubicin = 2 mg pyrrubicin = 2 mg daunorubicin = 0.5 mg normethoxydaunorubicin =
0.45 mg mitoxantrone; except doxorubicin liposomes);
6. Previous use of anti-HER2 therapy other than trastuzumab (eg, ADC, dual-antibody,
small molecule targeted therapy, etc.).
7. Pregnant or lactating women; or intend pregnancy during the trial or within 6 months
of the end of the trial;
8. Subjects with a history of life-threatening allergies or known allergies to protein
drugs or recombinant proteins or to one of excipients in KN026 drugs (histidine,
glacial acetic acid, sucrose, and polysorbate 20) who have had a severe
hypersensitivity reaction to trastuzumab.
9. Adverse events have not returned to CTCAE 5.0 grade = grade 1 or baseline from
previous anti-tumor treatments , except for alopecia, skin pigmentation and those
assessed by the investigators without potential safety risk.
10. Uncontrollable diarrhoea (=grade 2 that does not improve within 48 hours of
medication);
11. Subjects with the following history of cardiovascular disease:
- Subjects with uncontrolled hypertension (defined as sustained systolic blood
pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg despite
antihypertensive medication);
- Any history of symptomatic congestive heart failure (NYHA classification II-IV);
the absolute value of LVEF decreased by =10% and absolute value < 50% , or the
absolute value of LVEF decreased by =15% , during or after treatment with
trastuzumab or other anti-HER2 treatment;
- History of myocardial infarction within 6 months before treatment of the first
dose;
- Subjects with angina and unstable angina within three months prior to treatment
in the first dose;
- Severe arrhythmias and conduction abnormalities requiring antiarrhythmic therapy
other than ß-blockers or digoxin (except atrial fibrillation and paroxysmal
supraventricular tachycardia) within 6 months prior to treatment in the first
dose;
- QTcF > 450 ms (male); QTcF > 470ms (Female);
- Other heart diseases that the investigators consider clinically significant;
12. Poorly controlled systemic diseases judged by investigators, including diabetes;
13. Severe chronic or active infections requiring systemic antibacterial, antifungal, or
antiviral therapy (eg, anti-infective drugs have been used for more than 1 week before
the trial and will continue to be used), including tuberculosis infection;
14. Received systemic corticosteroids (> 10 mg/day of prednisone, or equivalent amounts of
other corticosteroids) within 2 weeks prior to treatment in the first dose; inhaled
steroids or topical cortisol is permitted, corticosteroids are allowed for
pre-treatment of certain chemotherapy drugs, and short-term (= 7 days) are allowed for
the prevention or treatment of contrast allergy;
15. History of noninfectious interstitial lung disease, or interstitial pneumonia
requiring hormonal therapy;
16. History of immunodeficiency, including HIV positive or other acquired or congenital
immunodeficiency disease, or a history of organ transplantation;
17. Active HBV [HBsAg or HBcAb-positive with HBV DNA > 500 IU/mL (or 2500 copies/mL)] or
HCV infection [subjetcs with polymerase chain reaction (PCR)-negative HCV ribonucleic
acid (RNA) can participate in this study] or HIV-positive or syphilis antibody
positive (confirmed);
18. History of any other malignant tumors within five years prior to the first dose,
except cured cutaneous squamous cell carcinoma, basal cell carcinoma,
non-muscle-invasive bladder cancer, localized low-risk prostate cancer [defined as
stage = T2a, Gleason score = 6, and PSA = 10 ng/mL at prostate cancer diagnosis (if
measured) who have received radical therapy and no biochemical recurrence of
prostate-specific antigen (PSA) can participate in this study], cervical/breast cancer
in situ who have received radical treatment without any signs of recurrence and
metastasis;
19. Cavity effusion (pleural effusion, ascites, pericardial effusion, etc.) requiring
drainage or diuretic therapy, within 2 weeks prior to the first dose of treatment;
Diuretics for other reasons are permitted;
20. Known mismatch repair deficient (dMMR) or highly unstable microsatellite (MSI-H)
without previous PD-1/PD-L1 monoclonal antibody therapy;
21. Unintentional weight loss of =5% within 1 month prior to the first dose, despite
peripheral or central venous nutritional support;
22. Inability to tolerate or refuse chemotherapy required by the protocol;
23. The investigator considered the subject to be unsuitable for participation in this
clinical study due to the presence of any clinical or laboratory abnormalities or
history of systemic disease or other reasons.
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