A Clinical Trial Evaluating IL-22BP/LNP Compound in Refractory Malignant Solid Tumors for Safety, Tolerability and Activity

Phase 1RecruitingNCT07100210

Xingchen Peng6 enrolled

Overview

This study aims to investigate the safety and efficacy of the IL-22BP/LNP compound in patients with refractory malignant solid tumors, such as advanced soft tissue sarcoma, advanced head and neck squamous cell carcinoma, and malignant melanoma, who have failed second-line treatment, have advanced recurrence or metastatic malignant solid tumors.

Cancer is a major cause of death among the global population and a significant obstacle to life extension. According to the statistics of the World Health Organization in 2019, it ranked as the first or second leading cause of death before the age of 70 in 112 countries, and in recent years, the burden of its incidence and mortality has increased rapidly. The treatment of advanced cancer consumes a large amount of resources, has poor efficacy, and is accompanied by numerous side effects. For example, the 5-year survival rate of advanced head and neck squamous cell carcinoma is only 40 - 50%, and radiotherapy may lead to osteonecrosis, while chemotherapy may cause hepatorenal toxicity and so on. Against this background, researchers have been exploring better treatment options, and gene therapy has attracted much attention. Messenger RNA (mRNA) is a crucial part of gene therapy, and immune gene therapy holds great potential. Interleukin-22 (IL-22) influences tumor development, and IL-22 binding protein (IL-22BP) can block its activity and impede the proliferation of tumor cells. Previously, there has been no research on mRNA vaccines targeting IL-22. Therefore, this project will provide a new treatment strategy for patients with advanced refractory malignant solid tumors.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Interventions

IL-22BP mRNA vaccine injectionBIOLOGICAL

During the injection of IL-22BP/LNP compound, there were two dose groups, namely 25 μg and 50 μg of mRNA, with three participants in each dose group, aiming to evaluate the safety and tolerability of the IL-22BP/LNP compound formulation. The treatment will be administered by intratumoral injection. Enrolled subjects will receive inoculations of IL-22BP/LNP compound injection according to their respective dose groups, which include 5 doses for basic immunization and subsequent personalized treatment. During the basic immunization, the first 4 doses will be given at an interval of 1 week each, and the 5th dose will be administered 1 month after the 4th dose.The entire treatment period lasts for 2 months.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Male or female patients: aged ≥ 18 years old and ≤ 70 years old; 2. Patients with histopathologically confirmed, refractory to second-line treatment, advanced recurrent/metastatic malignant solid tumors and without standard clinical treatment regimens (such as patients with advanced soft tissue sarcoma, advanced head and neck squamous cell carcinoma, malignant melanoma, etc.); 3. Eastern Cooperative Oncology Group (ECOG) performance status score: 0 - 1; 4. Expected survival time ≥ 3 months; 5. More than 28 days since the last chemotherapy/radiotherapy/surgery; 6. More than 6 weeks since the last use of nitrosoureas or mitomycin C; 7. Main organ functions are in good condition; 8. Sign a written informed consent form. Exclusion Criteria: 1. Have participated in other drug clinical trials within 4 weeks; 2. The tumor is located close to major blood vessels or the trachea; 3. Patients with uncontrolled cardiac clinical symptoms or diseases, such as heart failure of NYHA class II or above, unstable angina pectoris, having had a myocardial infarction within 1 year, and having clinically significant supraventricular or ventricular arrhythmias that require treatment or intervention. 4. For female subjects: pregnant or lactating women. 5. Patients have active tuberculosis, bacterial or fungal infections (≥ grade 2 of NCI-CTCAE 5.0); have active HIV infection, active HBV infection, or HCV infection. 6. Those with a history of psychotropic drug abuse who are unable to quit or have mental disorders; 7. Subjects have any active autoimmune diseases or a history of autoimmune diseases (such as, but not limited to: uveitis, enteritis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism; subjects with vitiligo or those whose asthma in childhood has been completely relieved and who do not require any intervention in adulthood can be included; subjects with asthma that requires bronchodilators for medical intervention cannot be included). 8. Subjects are currently receiving immunosuppressive treatment. 9. Have a history of drug abuse or known medical, psychological, or social conditions, such as a history of alcoholism or drug use. 10. Known to be allergic, hypersensitive, or intolerant to the studied IL-22BP/LNP (including any excipients). Have a severe allergy history to any drugs, foods, or vaccines in the past, such as anaphylactic shock, allergic laryngeal edema, allergic dyspnea, allergic purpura, thrombocytopenic purpura, local allergic necrotizing reaction (Arthus reaction), etc. 11. From the screening period to 12 months after the completion of drug injection, female subjects have pregnancy plans or the partners of male subjects have pregnancy plans. 12. According to the investigator's judgment, there are concomitant diseases that seriously endanger patient safety or affect the patient's completion of the study.

Outcomes

Primary Outcomes

Incidence of Dose-Limiting Toxicities and Treatment Interruptions Due to Adverse Events During the First Cycle of IL-22BP/LNP Treatment

Evaluate the incidence of dose-limiting toxicity (DLT) during the treatment with IL-22BP/LNP compound and the number of treatment interruptions due to treatment-related adverse reactions during the first treatment cycle.

Time frame: Participation in the whole process of the study.The entire treatment period lasts approximately 2 months.

Secondary Outcomes

Objective Response Rate(ORR)

It refers to the proportion of patients whose tumors have shrunk to a certain extent and remained so for a certain period of time. It is a direct indicator to measure the anti-tumor activity of drugs.It is usually calculated as the percentage of the sum of the number of patients with complete response (CR) and partial response (PR) in the total number of patients.

Time frame: From the time when the patients were enrolled in the study until one month after the last dose of the IL-22BP/LNP compound was injected.The time window is approximately 2 months.

Disease Control Rate (DCR)

It refers to the proportion of patients whose tumors have shrunk or remained stable. It reflects the control of tumor growth by treatment, including tumor shrinkage (as involved in ORR) and the situation where the tumor does not progress.It is calculated as the percentage of the sum of the number of patients with complete response (CR), partial response (PR), and stable disease (SD) in the total number of patients.

Time frame: From the time when the patients were enrolled in the study until one month after the last dose of the IL-22BP/LNP compound was injected.The time window is approximately 2 months.

Time to first complete remission (CR), partial remission (PR) on treatment with IL-22BP preparation.

Complete Response (CR): All target lesions disappear, no new lesions emerge, and tumor markers return to normal. This means that, from the perspective of imaging and relevant examinations, the tumor has completely vanished, and the patient's condition has achieved the most ideal improvement. For example, in the treatment of lymphoma, if enlarged lymph nodes completely disappear as detected by imaging examinations such as PET-CT, and relevant tumor markers in the blood also return to normal, it can be judged as a complete response.Partial Response (PR): The sum of the maximum diameters of target lesions is reduced by ≥ 30%, and no new lesions appear. Taking lung cancer as an example, if the sum of the maximum diameters of lung tumors is reduced by more than 30% after treatment and no new tumor lesions are detected, it is in a partial response state. This situation indicates that the tumor responds to the treatment and the patient's condition is under a certain degree of control.

Time frame: From the time when the patients were enrolled in the study until one month after the last dose of the IL-22BP/LNP compound was injected.The time window is approximately 2 months.

Duration of Response(DOR)

DOR is defined as the time between the first confirmation of CR, PR and the first disease progression or death from any cause.

Time frame: From the time when the patients were enrolled in the study until one month after the last dose of the IL-22BP/LNP compound was injected. The time window is approximately 2 months.

Duration of first confirmed disease stabilization

Defined as the time between the first confirmed stable disease (SD) and the first disease progression or death from any cause.

Time frame: From the time when the patients were enrolled in the study until one month after the last dose of the IL-22BP/LNP compound was injected.The time window is approximately 2 months.

Progression - Free Survival(PFS)

Defined as the time between first treatment with IL-22BP/LNP compound and first disease progression or death from any cause progression or death from any cause.

Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.

Overall Survival(OS)

OS defined as time from first treatment with IL-22BP/LNP compound to death from any cause.

Time frame: From date of randomization until the date of death from any cause, assessed up to 36 months.

A Clinical Trial Evaluating IL-22BP/LNP Compound in Refractory Malignant Solid Tumors for Safety, Tolerability and Activity

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts