Trial Title:
Clinical Study of SM3321 With Solid Tumors
NCT ID:
NCT06087770
Condition:
Locally Advanced or Metastatic Solid Tumors
Conditions: Official terms:
Neoplasms
Conditions: Keywords:
locally advanced
solid tumors
metastatic
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
SM3321
Description:
Intravenous infusion, once a week, 28 days for a dosing cycle
Arm group label:
Phase Ia Dose escalation
Summary:
The purpose of this study is to evaluate the Safety and Tolerability of SM3321 in
patients with locally advanced or metastatic solid tumors
Detailed description:
The goal of this clinical trial is to test patients with locally advanced or metastatic
solid tumors. The main questions it aims to answer are:
- To evaluate the safety and tolerability of SM3321 in patients with locally advanced
or metastatic solid tumors.
- To determine dose-limiting toxicities (DLTs) , Maximum tolerated dose(MTD) and
Recommended phase 2 dose (RP2D)of SM3321 in the treatment of patients with locally
advanced or metastatic solid tumors. .
- To evaluate the Pharmacokinetics (PK) profile of SM3321 in patients with locally
advanced or metastatic solid tumors after single and multiple administration.
- To evaluate the immunogenicity of single and multiple administration of SM3321 in
patients with locally advanced or metastatic solid tumors.
- To evaluate the initial antitumor activity of SM3321 in patients with locally
advanced or metastatic solid tumors.
- To further evaluate serum biomarkers and explore the potential relationship between
these markers and the antitumor activity and safety of SM3321.
- To explore the relationship between dose and/or PK exposure and effects(including
anti-tumor activity and safety).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Male or female aged 18 years or older.
2. Subjects with histologically or cytologically confirmed unrespectable locally
advanced or metastatic solid tumors.
3. The subject's disease progresses after receiving adequate standard treatment or is
intolerant to standard treatment or has no effective standard treatment options
available.
4. Subjects in this study must have at least one evaluable lesion (based on RECIST
v1.1).
5. Expected survival ≥12 weeks
6. ECOG PS score 0-2 points
7. The function of the major organs is basically normal, and the laboratory examination
within 7 days or less before the first administration meets the following standards:
a) Liver function:
- AST/ALT ≤ 2.5 × ULN (ULN= upper limit of normal);If liver metastasis occurs,
AST/ALT≤5×ULN;
- Serum total bilirubin ≤ 1.5 × ULN;Or in cases of Gilbert syndrome ≤3×ULN; b)
Blood routine (no hematopoietic growth factor or blood transfusion was used
within 2 weeks before enrollment) :
- Hemoglobin ≥ 90 g/L;
- Platelet count ≥100×10^9/L;
- Absolute neutrophil count ≥1.5×10^9/L. c) Kidney function:
- Creatinine clearance ≥50 mL/min (calculated by Cockcroft-Gault formula). d)
Coagulation function:
- International normalized ratio (INR) ≤1.5×ULN.
8. Female subjects of reproductive age must have a negative blood pregnancy test within
3 days prior to the first use of the study drug; Eligible subjects (men and women)
who are fertile (defined as sexually mature and biologically fertile) must agree to
use a reliable contraceptive method (hormonal or barrier method or abstinence, etc.)
with their partner during the study period and for at least 6 months after the last
dose.
9. Willing to participate in clinical research, understand and sign informed consent,
and follow up and abide by research procedures on time.
Exclusion Criteria:
1. Known allergy to SM3321 or its formulation components.
2. Previously received the following anti-tumor therapy:
1. Chemotherapy, targeted therapy, immunotherapy, or other anticancer therapy
within 28 days or 5 half-lives (whichever is shorter) prior to initial
administration of the investigational therapy, except for the following:
- anti-programmed death receptor-1 / programmed death receptor-ligand 1
antibodies used within 1.5 months;
- nitrosourea or mitomycin eluting period ≤6 weeks;
- Washout period of fluoropyrimidine or small molecule targeted drugs ≤5
half-lives or 2 weeks (whichever is longer);
- The washout period for herbal treatments with anticancer indications is ≤2
weeks.
2. Radiotherapy received within 4 weeks prior to the first dosing of the study
treatment, allowing a single fractionated radiotherapy for symptom relief.
3. The subject has participated in any other clinical study and received the trial
drug within 28 days prior to the first administration of the study drug.
3. Major surgery within 28 days before dosing or major surgery expected during the
study period.
4. There was acute toxicity from prior antitumor therapy that had not returned to ≤
grade 1 or baseline levels specified by the inclusion criteria prior to first
administration (based on NCI-CTCAE v5.0).
5. Uncontrolled or severe cardiovascular disease, including but not limited to any of
the following:
1. Prolonged QTc (using Fridericia's correction formula), male >450 ms/ female
>470 ms, or congenital long QT syndrome;
2. Left ventricular ejection fraction (LVEF) <50% was assessed by Multiple-gated
acquisition (MUGA) or ECHO;
3. any of the following in the 6 months prior to screening: > Grade 2 ventricular
arrhythmia, severe/unstable angina, congestive heart failure (New York heart
association (NYHA) III orGrade IV), coronary artery bypass grafting, myocardial
infarction, cerebrovascular accident, or transient ischemic attack;
4. Uncontrolled hypertension (systolic blood pressure >160 mmHg or diastolic blood
pressure >100 mmHg).If blood pressure can be controlled within the above limits
by antihypertensive therapy, subjects with a history of hypertension will be
admitted to the study.,
6. Concurrent history of severe chronic or active infection:
1. The subject has active hepatitis B, defined as:If HepatitisB surface antigen
(HBsAg) is positive, hepatitisB virus (HBV) Deoxyribonucleic acid (DNA) should
be tested for HepatitisB virus (HBV).HBV DNA was higher than the lower limit of
quantitative value.
2. The subject has active Hepatitis C, defined as: if Hepatitis C virus (HCV)
antibodies are positive, HCV Ribonucleic acid (RNA) should be tested, and
HCVRNA is positive;
3. Known to have Acquired immune deficiency syndrome (AIDS) or Human
immunodeficiency viru (Human immunodeficiency viru)Hiv-infected subjects may be
eligible for study participation if the CD4+ T cell count is ≥350 cells /µL and
there is no history of opportunistic infection as defined by AIDS.
4. other severe chronic infections, including but not limited to hospitalization
for infectious complications, bacteremia, severe pneumonia, or active
tuberculosis complications, within 4 weeks prior to initial administration of
SM3321;Or an uncontrolled active infection or unexplained fever >38 ° C
occurred within 7 days prior to first administration of SM3321.
7. Uncontrolled co-morbidities such as:
1. Subjects with known active primary tumors or metastases of the Central nervous
system (CNS);Note: Subjects with previously treated primary CNS
tumors/metastases may participate in the study, provided that they are
clinically stable for at least 2 weeks, have no evidence of new BMS or BMS
enlargement, and were first dosed with SM3321 The steroid dose was not
increased during the first 14 days to manage CNS symptoms.Subjects with
cancerous meningitis or pia spread or spinal cord compression were excluded
from this study even if clinically stable.
2. known to have other malignancies that are currently advanced or have required
aggressive treatment within the past 5 years (except for non-melanoma skin
basal cell carcinoma or squamous cell carcinoma, breast/cervical carcinoma in
situ, superficial bladder carcinoma and other in situ cancers that have been
treated radically and have no evidence of disease recurrence);
3. A history of symptomatic deep vein thrombosis or pulmonary embolism within 6
months prior to enrollment;
4. Significant malnutrition, such as the need for intravenous nutritional
solutions. Patients with stable malnutrition for more than 4 weeks after
correction before the first dose of the study drug could be enrolled;
5. Other acute or chronic medical conditions or abnormalities in laboratory
testing that may increase the risks associated with participation in the study
or use of the study product, or interfere with the interpretation of the study
results and, in the judgment of the investigator, render the subject ineligible
for participation in the study.
8. Pregnant or lactating women.
9. Have a history of active autoimmune disease, such as systemic lupus erythematosus,
rheumatoid arthritis, vasculitis, or have received long-term systemic steroid
therapy (at doses greater than 10 mg prednisone daily equivalent) or any other form
of immunosuppressive therapy within 14 days prior to the first administration of the
study drug. Exceptions include: clinically stable autoimmune thyroid disease;
Receive inhaled or topical corticosteroid therapy, such as intraocular,
intraarticular, and intranasal administration of prednisone equivalent ≤10 mg daily;
Short-term use of corticosteroids (no more than 7 days) for preventive treatment
(for example, to prevent hypersensitivity to contrast agents or non-autoimmune
allergic diseases);As well as replacement therapy (e.g., thyroxine for
hypothyroidism, insulin for diabetes, physiocorticoid replacement for adrenal or
pituitary insufficiency).
10. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem
cell transplantation.
11. Received systemic immunomodulatory drugs, such as thymosin, IL-2, and IFN, within 14
days prior to the first administration of the study drug.
12. People who have a clear history of mental disorders and take medication for
treatment.
13. People with a history of drug abuse or use.
14. Receive or will receive live vaccine within 30 days prior to the first dose of the
study drug, or plan to receive any live vaccine during the study.
15. The Investigator believes that the subject may have other factors that could affect
the study results and interfere with the subject's participation in the overall
study process, including previous or existing medical conditions, abnormal
treatments or laboratory tests, and the subject's unwillingness to comply with all
procedures, study restrictions and requirements.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Address:
City:
Guangzhou
Zip:
510120
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Zhihua Li
Phone:
+86-20-81248453
Email:
lzhdoct@163.com
Investigator:
Last name:
Zhihua Li
Email:
Principal Investigator
Facility:
Name:
Shanghai General Hospital
Address:
City:
Shanghai
Zip:
201210
Country:
China
Status:
Recruiting
Contact:
Last name:
Qi Li
Phone:
+86 18121288167
Email:
leeqi2001@hotmail.com
Investigator:
Last name:
Qi Li
Email:
Principal Investigator
Facility:
Name:
The second affiliated hospital Zhejiang university School of Medicine
Address:
City:
Hangzhou
Zip:
310009
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Hong Shen
Phone:
+86-571-8731 5108
Email:
shenhong0023@zju.edu.cn
Investigator:
Last name:
Hong Shen
Email:
Principal Investigator
Start date:
December 7, 2023
Completion date:
October 14, 2025
Lead sponsor:
Agency:
Beijing StarMab Biomed Technology Ltd
Agency class:
Industry
Source:
Beijing StarMab Biomed Technology Ltd
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06087770
