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

NCT05978102 | Recruiting Phase 1

• 1 other identifier: KY-2023-092
• Study Type: interventional
• Target: 183
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Number of participants of STI-7349 alone with treatment-related adverse events as assessed by CTCAE v5.0.

  Assessing the incidence of adverse events (AEs) of STI-7349 alone using the Common Terminology Criteria for Adverse Events (CTCAE Version 5.0)

  Up to 2 years.

• Number of participants of STI-7349 in combination with Pembrolizumab or other approved PD-1/PD-L1 inhibitors (e.g., Tislelizumab, etc.) with treatment-related adverse events as assessed by CTCAE v5.0.

  Assessing the incidence of adverse events (AEs) of STI-7349 in combination with Pembrolizumab or other approved PD-1/PD-L1 inhibitors (e.g., Tislelizumab, etc.) using the Common Terminology Criteria for Adverse Events (CTCAE Version 5.0)

  Up to 2 years.

Secondary Outcomes (39)

• To assess the AUC(Area under the concentration-time curve) of cationic lipids of STl-7349 alone in the treatment of advanced solid tumors

  The first four cycles(each cycle is 21 days).

• To assess the Tmax(Time to peak) of cationic lipids of STl-7349 alone in the treatment of advanced solid tumors.

  The first four cycles(each cycle is 21 days).

• To assess the Cmax(Peak concentration) of cationic lipids of STl-7349 alone in the treatment of advanced solid tumors.

  The first four cycles(each cycle is 21 days).

• To assess the AUC of mRNA(messenger-ribonucleic acid) of STl-7349 alone in the treatment of advanced solid tumors.

  The first four cycles(each cycle is 21 days).

• To assess the Tmax of mRNA of STl-7349 alone in the treatment of advanced solid tumors.

  The first four cycles(each cycle is 21 days).

Study Arms (3)

STI-7349 alone

EXPERIMENTAL

Dose escalation and dose expansion for STI-7349 alone,to determine the RP2D and to evaluate the preliminary antitumor activity of STI-7349 in specific solid tumor patients.

Drug: STI-7349

STl-7349 in combination with Pembrolizumab

EXPERIMENTAL

Dose escalation and dose expansion for STI-7349 in combination with Pembrolizumab,to determine the RP2D of STI-7349 in combination with Pembrolizumab and to evaluate the preliminary antitumor activity in specific solid tumor patients.

Drug: STI-7349; Drug: Pembrolizumab; Drug: Standard treatment（SoC）

STl-7349 in combination with other approved PD-1/PD-L1 inhibitors

EXPERIMENTAL

Dose escalation and dose expansion for STI-7349 in combination with with other approved PD-1/PD-L1 inhibitors (e.g., Tislelizumab, etc.), to determine the RP2D of STI-7349 in combination with Pembrolizumab and to evaluate the preliminary antitumor activity in specific solid tumor patients.

Drug: STI-7349; Drug: Standard treatment（SoC）; Drug: approved PD-1/PD-L1 inhibitors (e.g., Tislelizumab, etc.)

Interventions

STI-7349 DRUG

Administered by intravenous infusion (IV)

Also known as: IL2v mRNA

STI-7349 alone; STl-7349 in combination with Pembrolizumab; STl-7349 in combination with other approved PD-1/PD-L1 inhibitors

Pembrolizumab DRUG

Administered by intravenous infusion (IV)

Also known as: anti-PD-1 monoclonal antibody

STl-7349 in combination with Pembrolizumab

Standard treatment（SoC） DRUG

Depending on the treatment stage of enrolled subjects, the investigator will determine the standard treatment regimen and dosage with reference to the CSCO or other current guidelines.

Also known as: Standard treatment

STl-7349 in combination with Pembrolizumab; STl-7349 in combination with other approved PD-1/PD-L1 inhibitors

approved PD-1/PD-L1 inhibitors (e.g., Tislelizumab, etc.) DRUG

Depending on the treatment stage of enrolled subjects, the investigator will determine the standard treatment regimen and dosage with reference to the CSCO or other current guidelines or the corresponding drug Labeling.

STl-7349 in combination with other approved PD-1/PD-L1 inhibitors

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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.
• 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.

Sponsors & Collaborators

• The Fourth Affiliated Hospital of Zhejiang University School of Medicine: lead

Study Sites (1)

The Fourth Affiliated Hospital of Zhejiang University School of Medicine.

Yiwu, Zhejiang, China

RECRUITING

MeSH Terms

Interventions

pembrolizumab; spartalizumab; tislelizumab

Study Officials

• Kai Wang, Doctor(M.D.)

  The Fourth Affiliated Hospital of Zhejiang University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wang

CONTACT

13957158572; Doctorhuxi@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2023
• First Posted: August 7, 2023
• Study Start: August 23, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: July 23, 2025

Record last verified: 2025-07

Locations

CN (1)