A Study to Evaluate ABO2011 Monotherapy in Advanced Solid Tumors

Study Overview
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Brief Summary
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his is an open-label, single-arm, dose-escalation, and dose-expansion clinical study to evaluate the safety, tolerability, PK/PD, and preliminary efficacy of ABO2011 monotherapy in patients with advanced solid tumors who have progressed or metastasized after systemic standard of treatment.

Official Title
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A Phase I Clinical Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics (PK/PD) and Preliminary Efficacy of ABO2011 as Monotherapy in Patients With Advanced Solid Tumors Progressed or Metastasized After Systemic Standard Treatments

Conditions
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Solid Tumor, Adult

Intervention / Treatment
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* Drug: ABO2011 Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must be ≥18 years olde. Ability to sign informed consent, including compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and this protocol. Have histopathology or cytology confirmed progressed or metastatic Advanced solid tumors as by. Advanced solid tumors with disease progression or intolerable toxicity after prior systemic standard of treatment, or standard treatment is not available or does not exist. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. Expected survival greater than 12 weeks. At least one superficial or deep lesion for intratumoral injection and biopsy. At least one measurable lesion, as evaluated by the investigator, in addition to the presence of lesions that can be used for intratumoral injection of ABO2011. Meet the required level of organ function. Female patients are postmenopausal or, if women of childbearing potential, have a urine pregnancy or a blood pregnancy that is negative. At the same time, men of childbearing potential and women of childbearing potential voluntarily use effective contraception, including abstinence or effective contraception (e.g., intrauterine or implantable contraceptives, oral contraceptives, injectable or implantable contraceptives, extended-release local contraceptives, intrauterine devices [IUDs], condoms [males], diaphragms, cervical caps, etc.) from the time of signing the ICF until 120 days after the end of treatment. Exclusion Criteria: Other malignancies within the previous 5 years, with the exception of cured basal cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of breast, and carcinoma in situ of the cervix. Central nervous system tumors or metastases with clinical symptoms. History of serious cardiac disease, e.g., New York Heart Association (NYHA) ≥ Grade 2 cardiac failure, history of transmural myocardial infarction, unstable angina, poorly controlled arrhythmia, myocardial infarction within 6 months prior to enrollment, or arrhythmias requiring antiarrhythmic therapy (β-blockers, calcium channel blockers, and digoxin are allowed). Poorly controlled clinical complications, including, but not limited to, uncontrolled hypertension with both antihypertensive agents Hypertension and hypoglycemic treatment not Controlled type 2 diabetes, poorly controlled pleural, ascites, or other serious diseases requiring systemic treatment. Active autoimmune diseases and inflammatory diseases, such as systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory bowel disease and Hashimoto's thyroiditis, etc.; type 1 diabetes mellitus, hypothyroidism controlled by replacement therapy only, and skin diseases that do not require whole body therapy (eg, vitiligo, psoriasis) may be included in the trial. The subject carried: Known Human Immunodeficiency Virus (HIV); Active hepatitis B virus infection; Active hepatitis C virus infection. Thrombotic disease or use of full-dose anticoagulant drugs within 6 months prior to screening. Radiotherapy within 14 days prior to the first dose. Live or live attenuated vaccines or other vaccines within 30 days prior to the first dose may be determined by the investigator's comprehensive assessment. Major surgery within 28 days prior to the first dose or non-study-related minor surgery within 14 days prior to the first dose. Immunosuppressants or other immunomodulatory medications are required within 4 weeks prior to the first dose, but physiologic doses of systemic steroids are allowed or topical. Topical use should not exceed the dose recommended in the package insert or have any signs of systemic exposure; or other acquired, congenital immunodeficiency diseases, or a history of organ transplantation requiring the use of immunosuppressants or other immunomodulatory drugs. Acute toxic effects (CTCAE Grade ≥ 2) of prior anticancer chemotherapy or immunotherapy have not been stable, or significant post-treatment toxicities (except alopecia, peripheral neuralgia; and laboratory abnormalities above Grade 2 as mentioned in the inclusion criteria) have been observed. Any systemic anti-tumor therapy, within 28 days prior to the first dose or within 5 half-lives of prior anti-tumor drugs, whichever is shorter. Presence of clinically significant pulmonary fibrosis or interstitial pneumonia. Presence of active infections, including bacteria, fungi, viruses, and tuberculosis. Active bleeding, including but not limited to gastrointestinal bleeding, hemoptysis, etc. History of immediate severe allergic reactions prior to the first dose. Other conditions that may increase the risk associated with the study drug, or affect the study compliance, which the investigator considers unsuitable for participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABO2011 Injection<br> | Drug: ABO2011 Injection<br>* Name of Active Ingredient: mRNA encoding human single-chain IL-12 protein; ABO2011 injection Route of administration: intratumoral injection<br>* Other names: ABOD2011;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and character of DLTs |  | 21 days after the first dosing | 
| Incidence of Adverse Event (AE) |  | from informed consent until 28 days after the last administration | 
| Incidence of Serious Adverse Event (SAE) |  | from informed consent until 28 days after the last administration | 
| Incidence of patients with clinically significant abnormal laboratory results |  | from first dose until 28 days of last administration | 
| Maximum tolerated dose (if any) of ABO2011 monotherapy |  | 21 days after dosing of the last subject in the highest dose group |