Advanced malignant solid tumor
Conditions
Interventions
Dose escalation group:RGL-270 in combination with adalimumab
Dose expansion group:RGL-270 in combination with adalimumab
Sponsors
National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Pre screening Inclusion Criteria 1. The subjects should understand and comply with the relevant research procedures, and voluntarily sign the pre-informed consent form; 2. Age greater than 18 years (including the boundary value), gender not restricted; 3. Locally advanced or recurrent, metastatic advanced malignant solid tumors confirmed by histological or cytological examination; 4. Expected survival period >= 6 months; 5. Eastern Cooperative Oncology Group (ECOG) performance status score: 0 or 1 point; 6. Allowed for subjects with asymptomatic central nervous system (CNS) metastases (excluding meningeal or cerebrospinal fluid metastases), for those with symptomatic CNS metastases, they need to undergo local treatment and have stable condition for at least 7 days before the pre-screening without the need for steroids or anticonvulsant treatment (allowing preventive anti-epileptic medication); 7. Willing to provide sufficient tumor tissue specimens and peripheral blood for genetic testing and neoantigen analysis; 8. Female subjects with reproductive capacity and male subjects whose partners are women of childbearing age must agree to follow the contraceptive requirements from the time of signing the pre-informed consent form until 6 months after the last treatment. Screening Inclusion Criteria 1. The participants should understand and comply with the relevant research procedures, and voluntarily sign the primary informed consent form; 2. Eastern Cooperative Oncology Group (ECOG) performance status score: 0 or 1 point; 3. Patients with advanced malignant solid tumors who have completed standard treatment, or those who have no standard treatment or are intolerant to standard treatment; 4. Have assessable imaging lesions; 5. Willing to provide blood samples for each time used to detect immunogenicity and biomarkers before and after the treatment with the study drug; 6. The functions of important organs meet the following standards (no blood components or cell growth factors were used within 14 days before starting the study treatment): a) Blood routine: Neutrophil count (ANC) >= 1.0×10^9/L, lymphocyte count (LYM) >= 0.5×10^9/L, platelet count (PLT) >= 75×10^9/L, hemoglobin (Hb) >= 80g/L; b) Blood biochemistry: Total bilirubin (TBIL) = 30g/L, serum creatinine (Scr) = 50%; e) Electrocardiogram: Fridericia method-corrected QT interval (QTcF) < 470 milliseconds; The QTc interval must be corrected according to the Fridericia's standard, the correction formula is QTcF = QT/RR^0.33. 7. Female participants with reproductive capacity must undergo a serum pregnancy test 7 days before the first vaccine administration, and the result must be negative and must not be lactating.
Exclusion criteria
Exclusion criteria: Pre screening Exclusion Criteria 1. Have received immunotherapy with immune cells or tumor vaccines, including but not limited to tumor-infiltrating lymphocytes (TILs), chimeric antigen receptor T cells (CAR-T), T-cell receptor chimeric T cells (TCR-T), and therapeutic tumor vaccines; 2. Plan to receive a live attenuated vaccine during the screening period or during the study period and within 90 days after the end of the study drug treatment; 3. Any individuals assessed by the investigator as not suitable for immunotherapy; 4. Have an autoimmune disease (excluding those with hypothyroidism requiring hormone replacement therapy due to autoimmune thyroiditis or adrenal insufficiency requiring physiological hormone replacement therapy due to immune pituitaryitis); 5. Have a known history of epilepsy or other symptomatic neurological diseases; 6. Have a known history of substance abuse, alcoholism or drug abuse; 7. Have evidence of active tuberculosis infection within 1 year before the pre-screening period and during the pre-screening period, regardless of whether it has been treated; 8. Have known or suspected interstitial pneumonia, or have evidence of interstitial pneumonia on chest CT during the pre-screening period; have a known or suspected history of idiopathic pulmonary fibrosis, or history of organizing pneumonia (such as obliterative bronchiolitis or idiopathic organizing pneumonia); 9. Have another malignant tumor requiring treatment or with evidence of recurrence within 2 years before the pre-screening period (excluding non-melanoma skin cancer that has been surgically removed, cervical carcinoma in situ that has been cured, local prostate cancer, low-stage bladder cancer, and breast ductal carcinoma in situ); 10. Have a known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation; 11. Have an allergic reaction to the study drug or any of its excipients, or a history of severe allergic reaction to other vaccines; 12. Have congenital or acquired immune dysfunction, such as cellular immune deficiency (such as DiGeorge syndrome, severe combined immunodeficiency [SSCID] with T cells negative), or combined T and B cell immune deficiency (such as T- and B-negative combined immunodeficiency, Wiskott-Aldrich syndrome, ataxia telangiectasia, common variable immunodeficiency); or human immunodeficiency virus (HIV) infected individuals; 13. Pregnant or lactating female subjects; 14. The results of tumor tissue sequencing data analysis show that there are not enough neoantigens available for vaccine preparation or the vaccine preparation has failed; 15. The investigator judges that the subject is unable to continue participating in the study for the following possible reasons: - The subject has any other disease posing safety risks; - The subject has poor compliance or actively requests to withdraw from the pre-screening; - There is a sudden deterioration of the disease during the pre-screening period. Screening Exclusion Criteria 1. The adverse events caused by previous anti-tumor treatment have not recovered to <= CTCAE grade 1 (except for the organ functions as stipulated in the protocol, grade 2 peripheral neuropathy, hair loss and/or controlled hypothyroidism or adrenal insufficiency due to hormone replacement therapy, or type 1 diabetes well controlled by insulin), 2) They received radiotherapy or local treatment within 14 days before the first administration; 2. They received major surgery
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety;Incidence rate of dose-limiting toxicities.;RDE of RGL-270 combined with adebelestat treatment; | — |
Secondary
| Measure | Time frame |
|---|---|
| immunogenicity;Pharmacokinetics;Preliminary therapeutic effect; | — |
Countries
China
Contacts
Public ContactNing Li
Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Outcome results
None listed