A Clinical Trial of SIBP-A17 Injection in the Treatment of Advanced Solid Tumor Patients.

An Open Label, Multicenter Phase I Clinical Study Evaluating the Safety, Tolerability, and Pharmacokinetic Characteristics of SIBP-A17 Formulation for Injection in Subjects With Advanced Solid Tumors.

To evaluate the safety, tolerability, and pharmacokinetic characteristics of SIBP-A17 and determine the maximum tolerable dose (MTD) and phase II recommended dose (RP2D).

This study is an open, dose expanding, and indication expanding study to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, preliminary anti-tumor efficacy, QT/QTc interval effects and explore potential biomarkers of SIBP-A17 in patients with advanced solid tumors.

This study is divided into two stages and is planned to be set up six dose groups, including 1, 2, 4, 5, 6, and 8 mg/kg. The first stage is the dose escalation stage, adopting an improved "3+3" dose escalation design, with a planned enrollment of 14-36 participants. The second stage is the dose expansion stage, where one or two doses are selected to enter the dose expansion phase (4 indication cohorts). 20-40 late-stage solid tumor participants are enrolled in each dose group for dose expansion, and 80-160 participants are planned to be enrolled in the dose expansion phase.

After obtaining certain safety and pharmacokinetic data during the dose escalation phase, the Safety Monitoring Committee (SMC) can discuss and decide whether to synchronize dose expansion.

Inclusion Criteria:

• Age range of 18 to 75 years old (including boundary values), gender not limited.

• The clinical diagnosis of enrolled subjects should meet the following criteria:

  1. Dose escalation stage:

     Advanced solid tumor subjects confirmed by histology or cytology to have no standard treatment plan or ineffective or intolerant standard treatment plan.

  2. Dose expansion stage:

     • Cohort 1: Late/unresectable and/or metastatic breast cancer with low HER2 expression (IHC1+or IHC2+/FISH -) after standard treatment failure or intolerance.
     • Cohort 2: HER2 positive (IHC3+or IHC2+and FISH+) local advanced or metastatic digestive system tumors that fail or are not tolerated after standard treatment, including adenocarcinoma of stomach or gastroesophageal junction, colorectal cancer, etc. (pancreatic cancer and biliary tract cancer are excluded).
     • Cohort 3: HER2 positive (IHC3+or IHC2+with FISH+) advanced gynecological tumors that have failed or are intolerant to standard treatment, including but not limited to cervical cancer, endometrial cancer, and ovarian cancer.
     • Cohort 4: Other advanced solid tumors with HER2 expression that failed or were intolerant after standard treatment were preferentially included but not limited to HER2 positive (IHC3+or IHC2+and FISH+) breast cancer (at least 10 cases included), non-small cell lung cancer, etc.

• Willing and able to provide sufficient fresh collected or archived tumor tissue samples (only applicable during dose expansion phase).

• There must be at least one measurable lesion as the target lesion (according to RECIST v1.1 criteria, CT or MRI). Lesions that have received previous radiotherapy or other local treatments are not considered as target lesions unless there is clear progression of the lesion.

• The Eastern Cooperative Oncology Group (ECOG) score for physical fitness is 0 or Expected survival period ≥ 3 months.

• During the screening period, the main organ functions were basically normal [no blood transfusion, granulocyte colony-stimulating factor (G-CSF), or other medical support was received within 14 days before the use of the experimental drug]

• During the screening period, women of childbearing age with negative blood pregnancy test results and reproductive age subjects (including male subjects) who have no pregnancy plans during the trial period and within 6 months after the last dose and voluntarily take effective contraceptive measures.

• Voluntarily participate in this study and sign the informed consent form.

Exclusion Criteria:

• Patients with tumors as specified in the protocol
• Individuals with a history of previous treatment or surgery, or those who have received anti-tumor treatment as specified in the protocol during the planned trial period.
• Individuals with a history of previous illnesses or abnormal conditions as specified in the laboratory examination protocol.
• Screening for individuals with positive Treponema pallidum antibodies during the screening period. Individuals with active hepatitis B virus (HBV) or hepatitis C virus (HCV).
• Patients with ascites, pleural effusion, and pericardial effusion accompanied by clinical symptoms during the screening period who require drainage, or those who have undergone serosal fluid drainage within 4 weeks before the first administration.
• The screening period is accompanied by severe, progressive, or uncontrolled diseases, and it has been assessed by the researchers that participation in the study would increase the risk for the subjects.
• History of interstitial lung disease/non infectious pneumonia in the past, currently suffering from interstitial lung disease/non infectious pneumonia, or suspected interstitial lung disease/non infectious pneumonia that cannot be excluded through imaging examination during screening.
• Subjects who have experienced severe infections within 4 weeks prior to their first medication. Active infections that have received therapeutic intravenous antibiotics within 2 weeks prior to the first medication. Subjects receiving prophylactic antibiotic treatment can be enrolled.
• Participants who have participated in any clinical trial as subjects within the first 3 months of enrollment (excluding subjects who have only participated in clinical trial screening and have not used the investigational drug).
• According to the judgment of the investigator, there are concomitant diseases (such as severe diabetes, thyroid disease, etc.) that seriously endanger the safety of the subject or affect the completion of the study.
• Individuals with a history of severe allergies to protein products, CHO cell products, other recombinant human or humanized antibodies, or components of the investigational drug.
• Pregnant and lactating women.
• Researchers believe that participants who are not suitable for enrollment.