A Dose Escalation and Dose Expansion Clinical Study of STI-7349 in Subjects With Advanced Solid Tumors

Recruiting now · Phase 1/Phase 2

Conditions studied: Advanced Solid Tumor

In brief

This is a first-in-human, Phase Ⅰ, open-label, 2-period dose escalation and expansion study of STI-7349 administered intravenously to subjects with advanced solid tumors: * Period I is divided into two parts: Dose escalation for STI-7349 alone (1A) and dose expansion for STI-7349 alone (1B). In Part 1A, a rapid titration approach and traditional 3 + 3 trial design will be used to assess the safety, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), PK/biomarker profile, and to determine the recommended Phase 2 dose (RP2D) of STI-7349 alone; in Part 1B, an expansion study of STI-7349 alone will be conducted in target tumor types that may potentially benefit to assess the safety and preliminary efficacy of STI-7349 alone. * Period Ⅱ is divided into two parts: Dose escalation for STI-7349 in combination with Pembrolizumab (2A) or Other approved PD-1/PD-L1 inhibitors on the market (such as tislelizumab, etc.) and dose expansion for STI-7349 in combination with Pembrolizumab (2B) or Other approved PD-1/PD-L1 inhibitors on the market (such as tislelizumab, etc.). In Part 2A, a dose escalation study of STI-7349 in combination with Pembrolizumab or Other approved PD-1/PD-L1 inhibitors on the market (such as tislelizumab, etc.) is planned to be conducted using ½ RP2D of STI-7349 alone as the starting dose, which will use a traditional 3 + 3 trial design to assess the safety, DLTs, MTD, PK/biomarker profile of STI-7349 in combination with Pembrolizumab or Other approved PD-1/PD-L1 inhibitors on the market (such as tislelizumab, etc.) , and to determine the RP2D of STI-7349 in combination with Pembrolizumab or Other approved PD-1/PD-L1 inhibitors on the market (such as tislelizumab, etc.) ; in Part 2B, an expansion study of STI-7349 in combination with Pembrolizumab or Other approved PD-1/PD-L1 inhibitors on the market (such as tislelizumab, etc.) or add standard treatment on the basis of STI-7349 combined with pembrolizumab or Other approved PD-1/PD-L1 inhibitors on the market (such as tislelizumab, etc.) will be conducted in target tumor types that may potentially benefit to assess the safety and preliminary efficacy of the combination.

Key facts

Study ID

NCT05978102

Run by

The Fourth Affiliated Hospital of Zhejiang University School of Medicine

People needed

183

Starts

2023-08-23

Expected to finish

2027-06-01

Last updated by the study team

2025-07-23

Who can join

Age: 18 and older, up to 80. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• To be enrolled in this study, subjects must meet all of the following inclusion criteria:
• Subjects should have fully understood the study and voluntarily signed an informed consent form.
• Age 18 to 80 years (inclusive).
• ECOG(Eastern U.S. Oncology Collaborative Group) score of 0 to 1.
• Expected survival ≥ 12 weeks.
• According to Response Evaluation Criteria in Solid Tumors (RECIST1.1), the subject has at least one measurable lesion, that is, the subject has at least one lymph node lesion (minimum diameter ≥ 1.5 cm) or non-lymph node lesion (maximum diameter ≥ 1 cm) diagnosed by computed tomography (CT)/magnetic resonance imaging (MRI) examination; if the lesion that previously received local therapy (radiotherapy, ablation, vascular intervention, etc.) is the only lesion, there must be a clear imaging basis for disease progression of this lesion after local therapy.
• Subjects with malignant advanced solid tumors confirmed by histopathology or cytology who have failed standard treatment, or cannot tolerate standard treatment, or cannot obtain standard treatment for various reasons, or have no standard treatment.
• The subject has major organ function meeting the following criteria within 7 days prior to first dose [The subject had not received blood component transfusion within 14 days prior to testing. Subjects had not received supportive treatment with human granulocyte colony-stimulating factor (G-CSF), thrombopoietin (TPO), thrombopoietin receptor agonist, interleukin-11, and erythropoietin (EPO) within 7 days prior to testing.]:
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L;
• Platelet (PLT) ≥ 100 × 109/L;
• Hemoglobin (HGB) ≥ 90 g/L;
• Alanine aminotransferase (AST) ≤ 2.5 × ULN (≤ 5 × ULN(Upper limit of normal value) if liver involvement is known);
• Aspartate aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN if liver involvement is known);
• Total bilirubin (TBIL) ≤ 1.5 × ULN (≤ 3.0 × ULN if Gilbert's syndrome is diagnosed);
• Serum creatinine ≤ 1.5 × ULN or estimated glomerular filtration rate (eGFR, calculated according to the Cockcroft-Gault formula, or by measuring 24-hour urine) ≥ 40 mL/min;
• International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
• The toxic reaction of previous anti-tumor therapy returned to ≤ grade 1 (except for the following cases: Grade 2 neurotoxicity and grade 2 hypothyroidism caused by anti-tumor therapy, hair loss and pigmentation of any grade, grade 2 AE that cannot be returned to ≤ grade 1 and will remain stable for a long time as determined by the investigator based on the actual clinical situation, laboratory detection indicators are shown in inclusion Criterion 7) .
• Subject is willing and able to comply with the study schedule and all other study protocol requirements.
• Women of childbearing potential (women of non-childbearing potential are defined as sexually mature women who have undergone hysterectomy or bilateral oophorectomy or bilateral salpingectomy or bilateral tubal ligation/occlusion, or who are unable to have children because of congenital or acquired disease, or have natural menopause for ≥ 12 months) must have a negative blood pregnancy test during screening. Female subjects of childbearing potential and male subjects must use a highly effective method of contraception at screening through 6 months after the last treatment.

You may not qualify if…

• To be enrolled in this study, subjects must not meet any of the following exclusion criteria:
• The subject has a known hypersensitivity to any component of the investigational product or IL-2.
• Subjects have participated in any therapeutic clinical study within 28 days prior to first dose, were enrolled and treated. In addition, subjects are in the survival follow-up phase of observational or interventional studies.
• Subjects have used immunomodulatory drugs within 14 days or 5 half-lives (whichever is longer) prior to the first dose, including but not limited to thymosin, IL-2, IL-15, interferon, etc.
• The subject has received chimeric antigen receptor T-cell immunotherapy (CAR-T) within 3 months prior to the first dose; the subject has received chemotherapy (at least 6 weeks for chemotherapeutic agents nitrosoureas and mitomycin C, and at least 14 days for oral fluoropyrimidines), endocrine therapy, targeted therapy (washout period of 14 days or 5 half-lives for small-molecule targeted therapy, whichever is longer), immunotherapy (for immunomodulatory agents see exclusion criterion 3), tumor embolization, etc. within 28 days prior to the first dose; the subject has received radiotherapy within 14 days prior to the first dose, palliative radiotherapy for symptom control is allowed to be completed at least 7 days prior to the first dose; the subject has received traditional Chinese medicine for an approved indication of anti-tumor within 7 days prior to the first dose.Except when subjects assessed by the investigator could be enrolled.
• The subject has undergone major surgery within 28 days or minor surgery within 7 days prior to the first dose, or had an unhealed wound, ulcer, or bone fracture or required elective surgery during the study (except for diagnostic biopsy, insertion of vascular access device).
• Subjects have received a live attenuated vaccine within 28 days prior to the first dose or plan to receive it during the study.
• Subjects have received systemic immunosuppressants within 28 days prior to first dose excluding:
• Intranasal inhaled topical steroid therapy or topical steroid injection (eg, intra-articular injection);
• Systemic corticosteroid therapy not exceeding 10 mg/day prednisone or its physiologic equivalent doses;
• Corticosteroids as prophylaxis for allergic reactions (eg, premedication for CT);
• As prophylaxis for infusion reactions.
• See exclusion criteria 8 for systemic use of sex hormones in patients with brain metastases.
• Active central nervous system (CNS) metastases or cancerous meningitis with known or symptomatic symptoms at the screening stage (Note: ① Patients with CNS metastases with symptoms prior to initial administration who have been treated and stable for ≥4 weeks and have been off systemic sex hormone therapy (at any dose) for >3 days may be included. ②Asymptomatic brain metastases (i.e. no neurological symptoms, no need for corticosteroids, and no lesions >1.5cm) can be enrolled, but regular brain imaging examinations are required as a disease site).
• Subjects had uncontrolled third space effusions requiring repeated drainage, such as pleural effusion, ascites, pericardial effusion, etc. (subjects who do not require drainage of effusion or have no significant increase in effusion after stopping drainage for 3 days may be enrolled), or third space effusions that are bloody by diagnostic puncture.
• The subject had another malignancy within 5 years prior to the first dose, except for radically treated early malignancies (carcinoma in situ or Stage I tumor), such as adequately treated basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast after radical resection, early papillary thyroid carcinoma, or prostate cancer with local Gleason score ≤ 6.
• The subject had active autoimmune or inflammatory diseases, including inflammatory bowel disease (eg, ulcerative colitis or Crohn's disease), diverticulitis (other than diverticular disease), celiac disease, systemic lupus erythematosus, Sarcoidosis syndrome or Wegener' s syndrome (granuloma with polyangiitis), Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.), or a history of the disease within the previous 2 years (subject with vitiligo, psoriasis, alopecia, or Graves' disease not requiring systemic therapy within the last 2 years, hypothyroidism requiring thyroid hormone replacement therapy only, and Type 1 diabetes mellitus requiring insulin replacement therapy only may be enrolled).
• The subject has active or uncontrolled HBV（Hepatitis B Virus） (HBsAg positive and/or HBcAb positive and HBV DNA titer positive), HCV (HCV-Ab positive and HCV RNA titer positive), HIV(Human Immunodeficiency Virus) positive.
• The subject had an active bacterial, viral, or fungal infection (defined as a subject demonstrating persistent signs/symptoms related to infection that do not improve despite appropriate antibiotic or other therapy) or required intravenous (IV) antibiotics within 72 hours prior to the first dose.
• Severe or uncontrolled cardiovascular or cerebrovascular disease requiring treatment, including but not limited to:
• New York Heart Association (NYHA) cardiac functional classification > 2;
• Unstable angina not controlled by medication;
• Subject has had a myocardial infarction within 6 months prior to first dose;
• History of myocarditis;
• Cardiac tamponade;

Where it is running

• The Fourth Affiliated Hospital of Zhejiang University School of Medicine. — Yiwu, Zhejiang, China (enrolling)

Full record on ClinicalTrials.gov

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