Trial Title:
SG1906 for CLDN18.2-Positive Solid Tumors
NCT ID:
NCT05857332
Condition:
Locally Advanced Unresectable or Metastatic Solid Tumors
Conditions: Official terms:
Neoplasms
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
SG1906
Description:
Phase 1a will use an accelerated titration-Bayesian optimal interval (AT-BOIN) design
with 7 dose cohorts: 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 6 mg/kg, 9 mg/kg, and 12
mg/kg by IV infusion. Accelerated titration (i.e., 1 patient each) will be applied to the
first 2 cohorts.
Arm group label:
SG1906
Summary:
This is a Phase Ia/Ib Clinical Study to Evaluate the Safety, Tolerability,
Pharmacokinetics, and Preliminary Efficacy of SG1906 in Patients with CLDN18.2-Positive
Locally Advanced Unresectable or Metastatic Solid Tumors.
Detailed description:
After a screening period of up to 28 days for each study phase, qualified patients will
be enrolled to receive their assigned dose of SG1906, administered every 2 weeks (Q2W),
until disease progression or intolerable toxicity, starting of a new anticancer
treatment, withdrawal of consent, lost to follow up, death, or end of the study,
whichever occurs first.
Phase Ia: Dose-escalation Stage The study population in Phase Ia includes patients with
CLDN18.2-positive histologically or cytologically confirmed locally advanced unresectable
or metastatic solid tumor who have relapsed after standard therapy, have failed standard
therapy, are intolerant to standard therapy, are not eligible for standard therapy, or
refuse standard therapy. Phase Ib: Dose-expansion Stage The study population in this
phase will include patients with histologically or cytologically confirmed
CLDN18.2-positive locally advanced unresectable or metastatic G/GEJ cancer or PC who have
failed to respond to standard therapy, have relapsed after standard therapy, or are
intolerant to standard therapy; and who have disease progression as confirmed by the
Investigator or documented by medical history.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients must meet all the following criteria to be eligible for participation in
this study:
1. Understand and voluntarily sign the informed consent form (ICF).
2. Age ≥18 years.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
4. Expected survival time of ≥3 months.
5. Able to provide tumor tissue samples for CLDN18.2 detection.
6. Specific requirements for patients enrolled in Phase Ia and Phase Ib are as
follows:
Phase Ia Dose Escalation Phase
1. Patients with CLDN18.2-positive histologically or cytologically confirmed
locally advanced unresectable or metastatic solid tumor who have relapsed
after standard therapy, have failed standard therapy, are intolerant to
standard therapy, are not eligible for standard therapy, or refuse
standard therapy.
2. CLDN18.2 positivity is defined as H score ≥1 by central laboratory
immunohistochemistry.
Phase Ib Dose Expansion Stage
1. Patients with histologically or cytologically confirmed CLDN18.2-positive
locally advanced unresectable or metastatic G/GEJ adenocarcinoma or
pancreatic cancer who have failed to respond to standard therapy, have
relapsed after standard therapy, or are intolerant to standard therapy.
2. CLDN18.2 positivity is defined as H score ≥40 by central laboratory
immunohistochemistry.
7. At least one evaluable lesion (refer to Response Evaluation Criteria in Solid
Tumors, version 1.1 [RECIST 1.1]).
8. Adequate function of vital organs, defined as follows:
1. Bone marrow function (no transfusion, erythropoietin, granulocyte
colony-stimulating factor, or other medically supportive therapy within 7
days prior to the first dose): neutrophil count ≥1.5 × 109/L, platelet
count ≥100 × 109/L, and hemoglobin level ≥10.0 g/dL.
2. Adequate liver function, which must meet all of the following criteria:
- Serum total bilirubin ≤1.5 × upper limit of normal (ULN).
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
≤2.5 × ULN (AST and ALT ≤5 × ULN in patients with liver metastases).
- Albumin ≥3.0 g/L.
3. Renal function: serum creatinine ≤1.5 × ULN or endogenous creatinine
clearance ≥50 mL/min (Cockcroft-Gault formula).
4. Coagulation: international normalized ratio ≤1.5 × ULN or prothrombin time
≤1.5 × ULN, activated partial thromboplastin time ≤1.5 × ULN without
receiving anticoagulation therapy.
9. Toxicity caused by prior anti-tumor therapy recovered to Grade 0 to 1 (CTCAE
5.0), except for alopecia, Grade ≤2 sensory neuropathy, lymphocytopenia, and
endocrine disorders controlled with hormone replacement therapy.
10. Female patients of childbearing potential and male patients whose female
partners are of childbearing potential need to use at least one approved
contraceptive (e.g., intrauterine device, pill, or condom) during study
treatment and for at least 6 months (180 days) after the last dose; female
patients of childbearing potential must have a negative blood human chorionic
gonadotropin (HCG) test within 7 days prior to dosing and must not be
lactating.
11. Male patients must refrain from donating sperm from the time the ICF is signed
until at least 6 months after the last dose.
Exclusion Criteria:
Patients who meet any of the following criteria cannot be enrolled:
1. Presence of active central nervous system metastatic lesions; presence of metastases
to the brainstem or meninges, spinal cord metastases or compression. Exception:
patients with previously treated brain metastases (e.g., surgery, radiation therapy)
who are clinically stable for at least 4 weeks after treatment (calculated from the
first dose of investigational drug) and have discontinued corticosteroids for ≥14
days prior to the administration of investigational drug; patients with untreated,
asymptomatic brain metastases (i.e., no neurological symptoms, no need for
corticosteroids, brain metastases ≤1.5 cm in length, no significant edema around the
brain metastases).
2. Active autoimmune disease requiring systemic therapy within the past 2 years (e.g.,
use of immunomodulatory drugs, corticosteroids, or immunosuppressive medications);
related replacement therapy is allowed (e.g., thyroid hormone, insulin, or
physiologic corticosteroid replacement for renal or pituitary insufficiency).
3. Pyloric obstruction or any other condition that can cause long-term chronic nausea,
persistent recurrent vomiting (≥3 vomit episodes in 24 hours) or diarrhea.
4. Patients who have recently developed gastrointestinal bleeding (i.e., a history of
hematemesis, hematochezia, or melena within the past 3 months) without evidence of
recovery confirmed by endoscopy or colonoscopy; or patients with evidence of risk of
gastric bleeding.
5. Patients with active gastrointestinal disease including, but not limited to, gastric
or duodenal ulcers, acute gastric or intestinal perforation, acute necrotizing
pancreatitis, ulcerative enteritis, congenital megacolon or Crohn's disease.
6. Patients requiring long-term treatment with non-steroidal anti-inflammatory drugs
(NSAIDs); patients who are using anticoagulants such as heparin at therapeutic doses
or vitamin K antagonists (except for prophylaxis).
7. Presence of body fluid (hydrothorax, ascites, pericardial effusion, etc.) requiring
local treatment or repeated drainage.
8. Unintentional weight loss ≥5% within 1 month prior to initial dose, even with
peripheral or central intravenous nutritional support.
9. History of hemolytic anemia from any cause (including Evans syndrome).
10. History of defects in red blood cell production, hemoglobin production, or
metabolism, such as glucose-6-phosphate dehydrogenase deficiency, thalassemia,
sickle cell disease, and hereditary spherocytosis.
11. History of hemophagocytic lymphohistiocytosis.
12. Presence of active infection requiring antibiotic therapy within 2 weeks prior to
the first dose, except for prophylaxis.
13. Presence of cardiovascular system disease within 6 months prior to screening that
meets any of the following:
1. Cardiac function: congestive heart failure of New York Heart Association (NYHA)
class III or IV; left ventricular ejection fraction <50%.
2. Clinically significant cardiac disease or surgery within 6 months prior to the
first dose of the investigational drug, including myocardial infarction,
unstable angina pectoris, cerebrovascular accident, coronary/peripheral artery
bypass, etc.
3. QTcF (corrected QT interval with Fridericia formula) >450 ms in men and >470 ms
in women; history of clinically significant ventricular arrhythmias (e.g.,
sustained ventricular tachycardia, ventricular fibrillation, tip-twist
ventricular tachycardia); history or family history of congenital long QT
syndrome; arrhythmias requiring antiarrhythmic drug therapy (patients with
atrial fibrillation with controllable heart rate 1 month prior to the first
dose of the investigational drug may be enrolled).
4. History of arterial thrombosis, deep venous thrombosis and pulmonary embolism
within 6 months prior to the first dose.
14. Hypertension (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥90
mmHg) that has not been effectively controlled after treatment with standardized
antihypertensive medication.
15. Patients with active hepatitis B or C. In case of positive hepatitis B surface
antigen (HBsAg) or positive hepatitis B core antibody (HBcAb) during the screening
period, further hepatitis B virus (HBV) DNA titer testing must be performed (HBV
DNA≤200 IU/mL is required). Patients who are positive for hepatitis C virus (HCV)
must receive further HCV RNA testing (no higher than the upper limit of the
detection value at their study site); patients may be enrolled in the study only
after active hepatitis B or C requiring treatment has been excluded.
16. Known history of human immunodeficiency virus (HIV) infection (i.e., HIV antibody
positive);
17. Known history of Grade 3 to 4 hypersensitivity reactions to any biological product,
history of life threatening hypersensitivity reactions, or known hypersensitivity to
components of SG1906 drug product (Grade ≥3 hypersensitivity reactions).
18. Have received any of the following treatments or procedures:
1. Prior treatment with any antitumor therapy targeting CLDN18.2 or CD47
2. Patients who have undergone open surgery ≤3 months prior to the first dose
(except for surgeries for the purpose of biopsy).
3. Prior allogeneic organ grafting.
4. Systemic anticancer therapy (including chemotherapy, targeted therapy, hormonal
therapy and immunotherapy) within 28 days or 5 drug half-lives (whichever is
shorter) prior to the first dose of the investigational drug, and all AEs have
not returned to grade ≤1 (CTCAE 5.0), except for alopecia.
5. Radiotherapy ≤14 days prior to the first dose of the investigational drug;
palliative radiotherapy is allowed if it is completed within 2 weeks prior to
the enrollment in the study and radiotherapy-related toxicity has recovered to
grade ≤1 (CTCAE 5.0), except for alopecia
6. Any live vaccine within 4 weeks prior to the first dose of the investigational
drug
7. Have received treatment with various growth factors, blood transfusions or
other blood products for anemia or decreased platelet count within 14 days
prior to the first dose of the investigational drug.
19. Have received systemic corticosteroids (at a dose equivalent to >10 mg/day
prednisone) or other immunosuppressive drugs within 14 days prior to the first dose.
The following are permitted:
1. Topical or inhaled glucocorticoids in physiologic replacement doses are allowed
2. The use of short-course (≤7 days) corticosteroids at physiologic replacement
doses for the prevention or treatment of non-autoimmune diseases is allowed.
20. Any other condition that, in the opinion of the Investigator, may lead to
inappropriate participation in this study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Chinese PLA General Hospital
Address:
City:
Beijing
Zip:
100039
Country:
China
Status:
Recruiting
Contact:
Last name:
Jianming XU
Facility:
Name:
The First Affiliated Hospital Of Xiamen University
Address:
City:
Xiamen
Country:
China
Status:
Recruiting
Contact:
Last name:
Xin Zhao, 361003
Facility:
Name:
The Sixth Affiliated Hospital, Sun Yat-sen University
Address:
City:
Guangzhou
Zip:
510655
Country:
China
Status:
Recruiting
Contact:
Last name:
Yanhong Deng
Facility:
Name:
Henan Cancer Hospital
Address:
City:
Zhengzhou
Zip:
450003
Country:
China
Status:
Recruiting
Contact:
Last name:
Jufeng Wang
Facility:
Name:
The First Hospital of China Medical University
Address:
City:
Shenyang
Zip:
110002
Country:
China
Status:
Recruiting
Contact:
Last name:
Zhenning WANG
Contact backup:
Last name:
Funan LIU
Facility:
Name:
Liaoning Cancer Hospital
Address:
City:
Shenyang
Zip:
110801
Country:
China
Status:
Recruiting
Contact:
Last name:
Jingdong ZHANG
Facility:
Name:
Shanxi Cancer Hospital
Address:
City:
Taiyuan
Zip:
030013
Country:
China
Status:
Recruiting
Contact:
Last name:
Yusheng WANG
Facility:
Name:
The First Affiliated Hospital, Zhejiang University School of Medicine
Address:
City:
Hangzhou
Zip:
310003
Country:
China
Status:
Recruiting
Contact:
Last name:
Jian Ruan
Facility:
Name:
The Second Affiliated Hospital Zhejiang University School of Medicine
Address:
City:
Hangzhou
Zip:
310009
Country:
China
Status:
Recruiting
Contact:
Last name:
Ying Yuan
Start date:
May 30, 2023
Completion date:
August 30, 2025
Lead sponsor:
Agency:
Hangzhou Sumgen Biotech Co., Ltd.
Agency class:
Industry
Source:
Hangzhou Sumgen Biotech Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05857332
