| Eligibility |
Inclusion Criteria:
1. Males or females, of any race, age = 18 years;
2. Eastern Cooperative Oncology Group (ECOG) performance status = 1;
3. Willingness and ability to consent for self to participate in study and the ability to
comply with scheduled visits, treatment plan, laboratory tests, and other study
procedures;
4. Histologically confirmed advanced or metastatic cancer in patients who are refractory
to or intolerant to all available therapy. Patients who received prior PD-1/PD-L1
checkpoint inhibitor or prior CTLA-4 inhibitor therapy may enroll if they did not
experience Grade 3 immune-related toxicity (exceptions may be allowed provided these
toxicities have resolved e.g. Grade 3 endocrinopathy that is resolved or clinically
stable with hormone replacement therapy). There is no limit to the number of prior
treatment regimens;
5. At least one measurable lesion as defined by RECIST 1.1;
6. Resolution of all acute adverse events resulting from prior cancer therapies to
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
v5.0 Grade = 1 or baseline (except alopecia or neuropathy);
7. Considered by the Investigator to be an appropriate candidate for a Phase 1 clinical
study, with a life expectancy of = 12 weeks;
8. Adequate organ function as defined by the following criteria:
1. Absolute neutrophil count (ANC) = 1500/µL (=1.5 × 109/L) without growth factor
support for 7 days (14 days if on pegfilgrastim) prior to study treatment;
2. Platelets = 100,000/µL (= 100 ×109/L) without transfusion support within 14 days
prior to study treatment;
3. Hemoglobin = 9.0 g/dL without transfusion support within 14 days prior to study
drug administration (erythropoietin or darbepoetin permitted);
4. Adequate renal function and serum creatinine = 1.5 times the ULN or estimated
creatinine clearance = 30 mL/min by Cockcroft-Gault equation4;
5. Total serum bilirubin = 1.5 times the ULN, unless patient has documented
Gilbert's disease in which case bilirubin = 3.0 times the ULN;
6. Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase
[SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase
[SGPT]) = 2.5 times upper limit of normal (ULN) or = 5 times ULN in cases of
liver metastases
7. Albumin = 3.0 g/dL;
8. Prothrombin Time (PT) = 1.5 times the ULN, or 11 to 15 seconds in the absence of
a normal range; partial thromboplastin time (PTT) or activated partial
thromboplastin time (aPTT) = 1.5 times the ULN; and international normalized
ratio (INR) = 1.5 times the ULN unless the subject is receiving anticoagulant
therapy.
9. Subject with a QT interval corrected for heart rate using Fridericia's formula (QTcF)
and/or QT interval corrected for heart rate using Bazett's formula of < 470 msec for
both males and females;
10. A 28-day washout period after the completion of programmed death-1 (PD-1)/PD-L1
therapy;
11. Women of childbearing potential (WOCBP) must:
1. Agree to use at least 2 effective contraceptive methods (1 highly effective
method in combination with a barrier method; oral, injectable, or implantable
hormonal contraceptive; tubal ligation; intra-uterine device; barrier
contraceptive with spermicide; or vasectomized partner), one of which must be
barrier, from signing the ICF, throughout the study, and for up to 12 weeks
following the last dose of TJ210001;
2. Have a negative serum pregnancy test (sensitive of at least 25 mIU/ml) at
screening; and have a negative serum or urine pregnancy test (Investigator's
discretion) within 72 hours prior to Cycle 1 Day -1 of study treatment (note that
the screening serum pregnancy test can be used as the test prior to Day -1 study
treatment if it is performed within the prior 72 hours);
3. Avoid conceiving for 12 weeks after the last dose of TJ210001;
4. Avoid donation of ova from signing the ICF until 12 weeks after the last dose of
TJ210001;
5. Agree to ongoing urine pregnancy testing, if clinically indicated, during the
course of the study.
12. Males must agree to use a condom (a latex condom is recommended) during sexual contact
with a pregnant female or a female of childbearing potential and will avoid donation
of sperm or having a female partner conceive from the time of signing the ICF, while
participating in the study, during dose interruptions, and for at least 12 weeks after
the last dose of study treatment, even if he has undergone a successful vasectomy.
Exclusion Criteria:
1. Has an active autoimmune disease requiring systemic treatment within the past 2 years
(i.e., with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency) is not considered a form
of systemic treatment and is permitted;
2. Current treatment on another therapeutic clinical trial;
3. Receipt of systemic anticancer therapy, including investigational agents, within 28
days prior to study treatment (Note: if anticancer therapy was given within 28 days
prior to starting study treatment, patients are not excluded if = 5 times the
elimination half-life of the drug has elapsed.);
4. Prior treatment with C5aR inhibitors;
5. Prior T-cell or NK-cell therapy;
6. Major surgical procedure or significant traumatic injury within 4 weeks prior to study
treatment, and must have fully recovered from any such procedure; and no date of
surgery (if applicable) or anticipated need for a major surgical procedure planned
within the next 6 months (The following are not considered to be major procedures and
are permitted up to 14 days prior to study treatment: thoracentesis, paracentesis,
port placement, laparoscopy, thoracoscopy, tube thoracostomy, bronchoscopy, endoscopic
ultrasonographic procedures, mediastinoscopy, incisional biopsies, and routine dental
procedures. Core biopsy and skin biopsy do not require a waiting period prior to
dosing.);
7. Chest radiotherapy = 28 days, wide field radiotherapy = 28 days (defined as > 50% of
volume of pelvic bones or equivalent), or limited field radiation for palliation = 14
days prior to study treatment - such patients must have recovered adequately from any
side effects of such therapy;
8. Hypertension defined as blood pressure (BP) systolic > 150 or diastolic > 90 mm Hg
(Note: Initiation or adjustment of antihypertensive medication prior to study dosing
is allowed provided that the average of the three most recent BP readings prior to
study enrollment is = 150/90 mm Hg.);
9. Ascites, pericardial or pleural effusions that required intervention within 1 month
prior to study treatment;
10. Has known active CNS metastases and/or carcinomatous meningitis. Subjects with
previously treated brain metastases may participate provided they are radiologically
stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging
(note that the repeat imaging should be performed during study screening), clinically
stable and without requirement of steroid treatment for at least 14 days prior to
first dose of study treatment;
11. Any of the following in the previous 6 months: severe/unstable angina, myocardial
infarction (MI), symptomatic congestive heart failure, cerebrovascular accident,
transient ischemic attack (TIA), arterial embolism, pulmonary embolism, percutaneous
transluminal coronary angioplasty (PTCA), deep vein thrombosis, coronary artery bypass
grafting (CABG), or New York Heart Association (NYHA) Class 3 or 4 congestive heart
failure;
12. Has a diagnosis of immunodeficiency (known active HIV, hepatitis B virus, hepatitis C
virus infection) or is receiving chronic systemic steroid therapy (in dosing exceeding
10mg of prednisone equivalent) or any other form of immunosuppressive therapy within 7
days prior to the first dose of study drug;
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