| Eligibility |
Inclusion Criteria:
- 1. Female, age 18 ~ 75 (including both ends, or other age range required by local
regulations or IRB).
2. Patients must have histological confirmed locally advanced or metastatic TNBC:
a) The primary or metastatic lesions were pathologically confirmed to be triple
negative, that is, negative for ER, PR and HER-2. Negative ER and PR are defined as ER
< 1% positive and PR < 1% positive. HER-2 negative is defined as: immunohistochemical
detection of HER-2 (-) or (1 +), HER-2 (2 +) must be tested for FISH and the result is
negative, HER-2 (1 +) can be selected for FISH test and the result is negative, and
metastatic pathology is preferred b) Patient must have at least 1 measurable lesion
(by RECIST V1.1) c) Patient must progress after first-line and not more than
second-line systematic treatment d) Patient must agree to undergo a tumor biopsy in
the study e) Previous tumor tissue samples that meet the requirements should be
provided during the screening period, or tumor biopsies should be performed before the
first treatment.
3. ECOG performance status 0~1 4. Life expectancy = 12 weeks 5. Adequate organ
function and bone marrow function as indicated by the following screening assessments
performed within 14 days before the first dose of study drug (without blood
transfusion or medication with stimulation factors within 14 days before 1st dose) :
1. Absolute neutrophil count (ANC) =1.5×109/L
2. Platelet count (PLT) =100×109/L
3. Hemoglobin (Hb) =90 g/L
4. Total bilirubin (TBIL) =1.5×ULN
5. Aspartate transaminase (AST) and alanine transaminase (ALT), =2.5 ×ULN (for the
patient with liver metastasis in escalation part or patient in expansion part:
AST and AST =5×ULN)
6. Serum creatinine (Cr) =1.5×ULN or creatinine clearance (Crcl) =50mL/min based on
Cockcroft-Gault formula 6. Female patients of childbearing potential must agree
to use effective methods of birth control during the study and for up to 6 months
after the last dose of study drug. Non-surgically sterilized female patients of
childbearing potential must be in non-lactation period, and have a negative ß-HCG
test result within 7 days before first administration.
7. Patient should understand, sign, and date the written voluntary informed
consent form prior to any protocol-specific procedures performed. Patient should
be able and willing to comply with study visits and procedures as per protocol.
Exclusion Criteria:
- 1. Patients who are known to be allergic to any component of X4P-001 or triplizumab or
have previously developed severe allergic reactions, rapid allergic reactions or other
hypersensitivity to peptides, chimeric or humanized antibodies, fusion proteins 2.
Patients who suffer from other malignant tumors within 5 years before enrollment
(except: radical cervical carcinoma in situ or non-melanoma skin cancer; second
primary cancer that has been cured and has no recurrence within five years; the
researchers believe that both primary cancers can benefit from this study; the
researchers have clearly confirmed which primary tumor source the metastatic focus
belongs to).
3. Patients with primary central nervous system malignant tumor; patients with central
nervous system metastasis who failed local treatment; (patients with asymptomatic
brain metastasis, or patients with stable clinical symptoms and without steroids and
other treatment for brain metastasis for more than 28 days can be included in the
group. ).
4. Patients who use cytochrome P450 (CYP) 3A4, strong 2D6 inhibitors or inducers (see
12.4, including prohibited foods) and antacids before the first use, and the last use
is less than 14 days or 5 half-lives from the first use, whichever is the shorter.
5. Patient who RANKL ligand inhibitors were used within 1 month before the first
administration of the study drug or are expected to be used during the study period
(e.g. deschumab, etc.) 6. Patients who systemic immunosuppressive drugs (including,
but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate,
thalidomide, etc.) are used within 2 weeks prior to the first administration of
research drugs, or systemic immunosuppressive drugs are known to be required in the
course of research treatment, unless:
1. Patients who receive short-term, low-dose systemic immunosuppressive drugs or
patients who receive one-time systemic immunosuppressive drug pulse therapy (such
as corticosteroids for 48 hours for the treatment of contrast medium allergic
reactions, single use of cyclophosphamide during induction of tumor therapeutic
vaccine)
2. Patients who receive corticosteroids in the treatment of chronic obstructive
pulmonary disease or asthma, or low-dose corticosteroids in the treatment of
orthostatic hypotension or adrenal insufficiency are allowed to enter the group
7. Previous anti-cancer therapy prior to initiation of study treatment: major
surgery (except palliative therapy), radiotherapy (bone-marrow exposure
>30%);routine chemotherapy, targeted therapy, immunotherapy is less than 4 weeks
(chemotherapy with nitrosourea or mitomycin <6 weeks); endocrine therapy within =
5 half-life or = 14 days (whichever is shorter).
8. Patients who are unable to take oral drugs or there are factors that
significantly affect oral drug absorption, such as gastric remnant dysfunction
after previous total gastrectomy or subtotal gastrectomy, short bowel syndrome
after small bowel resection, active diarrhea or irritable bowel syndrome
requiring drug treatment, etc.
9. Patients with previous organ transplants 10. Patients with definite active
infection or fever of unknown origin > 38.3 ? within 4 weeks before receiving the
first study drug and were treated with oral or intravenous antibiotics.
11. Patients who had previously participated in other clinical studies were
included in the original clinical study and less than 28 days after the first
administration of the drug in this study.
12. Patients whose adverse events caused by previous antineoplastic therapy did
not recover to = grade 1 (CTCAE5.0) (except for alopecia, vitiligo, = grade 2
neurotoxicity and other events that researchers believe do not affect the safety
evaluation of patients and research drugs).
13. Impaired cardiac function or clinically significant cardiac disease,
including any of the following:
a) New York Heart Association class III or IV congestive heart failure, unstable
angina, or myocardial infarction within 6 months before administration of the study
drug; b) Clinically significant cardiac arrhythmia requiring active therapy; c)
Uncontrolled hypertension; d) Left ventricle ejection fraction<50%; e) Prolongation of
QTcF (average of three times of examine, male > 450 ms, female > 470 ms) (Note: QTc
interval corrected by Frederica's formula) at screening, and other ECG abnormalities
with clinical significant by the judge of the investigator.
14. Patients with a history of interstitial pneumonia 15. Patients were positive for
(HIV) antibody of human immunodeficiency virus, (HCV) antibody of hepatitis C virus
and (TP) antibody of Treponema pallidum, and (HBV) surface antigen of hepatitis B
virus was positive and HBVDNA = 1000IU/ml. The subjects are in active stage of
tuberculosis; (antiviral therapy is allowed during the trial of subjects with positive
(HBV) surface antigen of hepatitis B virus).
16. Any other clinically significant comorbidities, such as respiratory, metabolic,
congenital, endocrine or central nervous system disease, or any other medical
conditions, mental disturbances or social determinants, which in the judgment of the
Investigator, could compromise compliance with the protocol, interfere with the
interpretation of study results, or predispose the patient to safety risks.
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