The Phase I Study of SIG001 Antibody on Cancer Therapy. | NCT07486700

Name	Class
Peking Union Medical College Hospital	OTHER
First Affiliated Hospital of Zhejiang University	OTHER
Tianjin Medical University Cancer Institute and Hospital	OTHER

Description Module

Label	Type	Description	Intervention Names
Dose-escalation study group	Experimental	In is group of study, the safty characteristics of SIG001 will be determined by escalating dosage of SIG001. 36 patients will participate in this group.	Biological: SIG001
Dose Expansion Study Group	Experimental	In this group of study, the Recommended Phase II dose of SIG001 will be determined. 30 patients will join this group.	Biological: SIG001

Name	Type	Description	Arm Group Labels	Other Names
SIG001	Biological	Intravenous administration. The dose-escalation study was conducted using a BOIN design. The starting dose in the escalation regimen was 0.15 mg/kg Q2W. The dose increases were at rates of 167%, 150%, 80%, 94.4%, and 71.4%, respectively, until a dose of 6 mg/kg was reached.

Measure	Description	Time Frame
DLT	Dose limited toxicity evaluated in the first cycle of treatment	up to 28 days
Maximum Plasma Concentration [Cmax]	Maximum Plasma Concentration [Cmax]	up to 28 days
incidence rate of Adverse events	incidence rate of Adverse events occured during treatment	up to 28 days

Measure	Description	Time Frame
Tumor assessment	Tumor effect assessment according to CT/MRI	up to 56 days

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subjects must meet all of the following criteria to be eligible for this clinical study:
1. The subject must fully understand the requirements of this study and voluntarily sign a written informed consent form. They must also be able to comply with the study's medication regimen as well as all related procedures and assessments;
2. Age must be >=18 and <=75 years old, with no gender restriction;
3. Subjects must have locally advanced, recurrent, or metastatic malignant tumors that have failed standard treatment or are not tolerant to it, and for which there is no effective standard treatment option. Histological or cytological confirmation is required;
4. According to RECIST v1.1, the subject must have at least 1 measurable target lesion. At baseline, the lesion must be accurately measurable by computed tomography (CT) or magnetic resonance imaging (MRI) - preferably with intravenous contrast agent. The long diameter of non-lymph node lesions must be ≥10 mm, and the short axis of lymph node lesions must be >=15 mm. The lesion must be suitable for repeated and accurate measurements. If a lesion in a previously irradiated area shows clear progression, it can also be considered a measurable target lesion;
5. The expected survival time must be >=12 weeks;
6. The Eastern Cooperative Oncology Group performance status score must be 0 or 1;
7. Subjects must have adequate function of vital organs at the time of screening. This requires that no blood transfusions, hematopoietic stimulants, or human albumin preparations have been used within 14 days prior to screening. The specific criteria are as follows:
1. Blood tests: Absolute neutrophil count >=1.5 × 10^9/L; Platelet count >=75 × 10^9/L; Hemoglobin >=90 g/L;
2. Liver function: Serum TBIL <=1.5 × ULN. For patients with liver metastases or Gilbert's syndrome, TBIL <=3 × ULN. For subjects without liver metastases, ALT and AST <=2.5 × ULN; for those with liver metastases, ALT and AST <=5 × ULN;
3. Coagulation function: Activated partial thromboplastin time and International normalized ratio <=1.5 × ULN (for subjects on anticoagulant therapy, these values must be within the therapeutic range).
4. Renal function: Creatinine clearance rate >=60 mL/min, calculated using the Cockcroft-Gault formula;
5. Cardiac function: Echocardiography shows left ventricular ejection fraction greater than 50%; 8. Female subjects of childbearing age must have a negative pregnancy test within 7 days before receiving the study drug for the first time. Eligible male and female subjects must agree to use reliable contraceptive methods (hormonal, barrier methods, or abstinence) during the study and for at least 6 months after the last dose of the drug. Eligible subjects are defined as being sexually mature and biologically capable of reproducing.

Exclusion Criteria:

Subjects will be excluded if they meet any of the following criteria:
1. SIG001 is administered during the washout period following previous antineoplastic therapy (4 weeks or 5 half-lives after the last dose, whichever is shorter);
2. Received radiotherapy within 28 days prior to the first dose of SIG001;
3. Acute toxicity resulting from previous antineoplastic therapy had not resolved to NCICTCAE 5.0 version grade ≤1 or to the baseline level specified in the inclusion criteria 4 weeks before the first dose of SIG001 (excluding hair loss or fatigue);
4. Had a history of other malignant tumors within 5 years prior to the first dose (except for non-melanoma skin basal cell carcinoma or squamous cell carcinoma that has been cured with no evidence of recurrence, breast/cervical carcinoma in situ, superficial bladder carcinoma, and other in situ cancers);
5. Subjects with any of the following cardiovascular diseases:
1. Symptomatic heart failure (New York Heart Association functional class >=2, see Appendix 4);
2. Uncontrolled hypertension despite standard treatment (systolic blood pressure >=160 mmHg or diastolic blood pressure >=100 mmHg);
3. Resting mean corrected QT interval > 470 ms on a 12-lead electrocardiogram (QTc, using Fridericia's correction formula) on three repeated measurements. Various clinically significant arrhythmias, conduction abnormalities, and resting ECG abnormalities, such as complete left bundle branch block, third-degree block, second-degree block, and PR interval > 250 ms. Factors that may increase the risk of QTc prolongation or arrhythmic events, such as heart failure, hypokalemia, congenital long QT syndrome, a family history of long QT syndrome or sudden death before age 40, and use of medications known to prolong QTc;
4. Acute coronary syndrome/acute myocardial infarction, unstable angina pectoris, percutaneous coronary intervention or coronary artery bypass grafting within 6 months prior to screening;
5. Any cause of cardiomyopathy;
6. Clinically significant valvular heart disease;
7. History of atrial or ventricular arrhythmias that require treatment; subjects with atrial fibrillation and well-controlled ventricular rate may be enrolled;
8. Transient ischemic attack or stroke within 6 months prior to screening; 6. Subjects with infectious diseases, including;
1. Acute or chronic active hepatitis B, defined as positive for hepatitis B surface antigen (HbsAg) and/or hepatitis B core antibody (HbcAb) with HBV DNA >=100 IU/mL;
2. Acute or chronic active hepatitis C, i.e., positive for HCV antibodies with HCV-RNA levels above the upper limit of the central reference range;
3. HIV-infected individuals (positive for HIV 1/2 antibodies);
4. Active syphilis or active pulmonary tuberculosis; 7. Subjects with primary central nervous system tumors, meningeal metastases, spinal cord compression, or brainstem metastases; those with untreated brain metastases or symptomatic/stable conditions can be enrolled after at least 4 weeks of stable treatment; 8. Uncontrolled comorbidities, such as:
1. Severe infections within 4 weeks prior to study initiation, including hospitalization due to infection, bacteremia, or severe pneumonia; subjects with uncontrolled active infections during screening can be enrolled if they receive prophylactic antibiotics (e.g., for urinary tract infections or chronic obstructive pulmonary disease);
2. History of interstitial lung disease, unresolved radiation pneumonitis, acute episodes or progressive worsening of pulmonary symptoms at baseline, or factors that increase the risk of interstitial lung disease and pose a safety risk to the subject as assessed by the investigator;
3. Severe malnutrition requiring intravenous nutrition; subjects whose malnutrition has been corrected and stabilized for more than 4 weeks prior to the first dose can be enrolled;
4. Tumors invading vital organs or blood vessels, which may significantly increase treatment risk or affect efficacy assessment; subjects with a risk of esophagotracheal fistula or esophagothoracic fistula, or those within 4 weeks of esophageal or tracheal stent placement (subjects with stable conditions for more than 4 weeks can be enrolled);
5. History of gastrointestinal perforation and/or fistula within 6 months prior to screening;
6. Presence of uncontrolled effusions requiring repeated drainage, such as pleural effusion, ascites, pericardial effusion, etc. (Subjects without the need for drainage or with no significant increase in effusion volume after 3 days of drainage cessation can be enrolled).
9. Subjects who are expected to receive other antineoplastic treatments during the study period (palliative radiotherapy is allowed); 10. Subjects who have participated in clinical studies within 4 weeks prior to the first dose or plan to participate in other clinical studies during the study period; 11. Subjects who have received live vaccines within 4 weeks prior to the first dose; 12. Allergy to SIG001 or its components; 13. Pregnant women, lactating women, or women who plan to become pregnant during the study period; 14. History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation; 15. Subjects who have received systemic immunosuppressive therapy for autoimmune diseases within 2 years prior to dosing are excluded, except in the following cases:
1. Inhaled, topical, or intramuscular steroid use;
2. Systemic corticosteroids (dose not exceeding 10 mg/day of prednisone or equivalent);
3. Steroids used as premedication for hypersensitivity reactions (e.g., premedication for CT scans).
16. Subjects with a history of mental disorders and those taking medication for treatment; 17. Subjects with a history of drug abuse or substance use; 18. Subjects who, in the judgment of the investigator, have other factors that may affect the study results or interfere with their participation in the entire study, including past or current health conditions, treatment or laboratory test abnormalities, and those who are unwilling to comply with the study procedures and requirements.