Malignant solid tumors at high risk of recurrence after radical treatment
Conditions
Interventions
Increase the dose of single-drug treatment (Part A):Preset the dose group, adopt the Bayesian optimal interval (BOIN) design, and increase the dose from low to high.
Combined treatment dose increase (Part B):The combined therapeutic dose of RGL-270 combined with fixed doses of adebelimab was increased.
Combined treatment dose expansion (Part C):RGL-270 recommended extended dose (RDE) combined with fixed dose of adebelimab treatment determined by Part B.
Sponsors
Fudan University Shanghai Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Pre-screening period 1. Subjects should understand and abide by the relevant research procedures, and voluntarily sign the prior informed consent form; 2. Age 18-75 years old (including boundary value), gender is not limited; 3. For malignant solid tumors confirmed by histology or cytology after radical resection, the subjects are allowed to complete standard adjuvant treatment, or no standard adjuvant treatment, or adjuvant treatment intolerance before receiving the first administration of this study: (1) Pancreatic ductal adenocarcinoma: R0/R1 resection, TNM stage I-III (T1-3, N0-2, M0), postoperative adjuvant chemotherapy based on gemcitabine or fluorouracil (5-FU, capecitabine or S-1); (2) Non-small cell lung cancer: There is no EGFR exon 19 deletion mutation or exon 21 point mutation (L858R) and ALK gene fusion. After TNM stage IIA (T2b, N0), IIB, IIIA, IIIB (N2) radical resection (R0 resection), if you receive neoadjuvant therapy, Postoperative pathology showed that no pathological complete response (pCR) was achieved, and platinum-based doublet chemotherapy or immune monotherapy was completed. Note: pathologic complete response (pCR) refers to the absence of any residual tumor cells in all resected specimens of lung cancer, including regional lymph nodes, after complete evaluation of hematoxylin-eosin stained sections. (3) Limited-stage small cell lung cancer (LS-SCLC) : stage I-iia (T1-2N0M0) underwent radical resection, followed by etoposide + cisplatin/carboplatin chemotherapy. (4) Locally advanced gastric cancer and gastroesophageal junction cancer: TNM stage II-IVA (ct1-2N +M0 or ct3-4b, any N, M0), D2 radical resection, postoperative fluoropyrimidine and platinum-based adjuvant chemotherapy; (5) Hepatocellular carcinoma Barcelona Clinic Liver Disease stage B/C, liver function Child-Pugh class A, radical resection or ablation with the purpose of radical treatment, And with tumor rupture, tumor diameter > 5 cm, tumor number > 3, microvascular invasion, macrovascular invasion, lymph node metastasis, and one of the Edmondson grade ?-? factors of tissue differentiation; There is no international standard adjuvant therapy, and patients can directly enter the study after surgery. (6) Muscle invasive bladder urothelial carcinoma: patients with TNM stage II-IVA (T2-4 or N+, M0) after standard radical cystectomy, if they received platinum-based neoadjuvant chemotherapy before operation, they could enter the study directly after operation or after completion of nivolumab treatment. If patients did not receive neoadjuvant chemotherapy before surgery, platinum-based adjuvant chemotherapy was completed after surgery. (7) Colorectal cancer: TNM stage II (pMMR), III, or metastatic colon cancer with R0 resection, and postoperative chemotherapy with fluorouracil alone or combination chemotherapy containing fluorouracil and platinum; (8) Malignant melanoma: including stage IIB-III cutaneous melanoma and toe-tip melanoma and stage I-III mucosal melanoma without BRAF V600E mutation, cutaneous melanoma and toe-tip melanoma could be enrolled directly after surgery. Either adjuvant pembrolizumab or adjuvant interferon was completed. Patients with mucosal type need to complete temozolomide and cisplatin adjuvant chemotherapy after surgery. (9) Renal clear cell carcinoma: pathological WHO/ISUP nuclear grade 3-4, or TNM stage III-IV and M0 (T3-4, or N1, M0), can be directly enrolled in the study after surgery. (10) Other malignant solid tumors: in
Exclusion criteria
Exclusion criteria: Pre-screening period 1. Have received immune cell or tumor vaccine treatment, including but not limited to tumor infiltration lymphocytes (TILs), chimeric antigen receptor T cells (CAR-T), T cell receptor chimeric T cells (TCR-T) and therapeutic tumor vaccines; 2. Plan to inoculate live attenuated vaccine during the screening period or during the research period and within 90 days after the end of the research drug treatment (inactivated vaccine is allowed); 3. Anyone who is evaluated by researchers as not suitable for immunotherapy; 4. There is an autoimmune disease (except for hypothyroidism who need hormone replacement treatment caused by autoimmune thyroiditis); 5. Known history of epilepsy or other symptomatic neurological diseases; 6. Known history of psychotropic substance abuse, alcoholism or drug abuse; 7. There is evidence of active tuberculosis infection within 1 year before the pre-screening period and during the pre-screening period, whether it is treated or not; 8. Subjects with known or suspected interstitial pneumonia, or evidence of interstitial pneumonia in the chest CT during the pre-screening period; known history of idiopathic pulmonary fibrosis, mechanized pneumonia (such as occlusive bronchitis or occult mechanized pneumonia); 9. Combined history of other malignant tumors within 5 years before the pre-screening period; 10. Known history of allogeneic organ transplantation or history of allogeneic hematopoietic stem cell transplantation; 11. Known allergy to research drugs or any of their auxiliaries, or a history of severe allergic reactions to other vaccines; 12. Suffering from congenital or acquired immunodeficiencies, such as cellular immunodeficiencies (such as DiGeorge syndrome, T-negative severe combined immunodeficiency [SSCID]) or combined T-cell and B-cell immunodeficiency (such as T- and B-negative combined immunodeficiency, Wiskott-Al Drich syndrome, ataxia telangiectasia, common variable immunodeficiency); or infected with human immunodeficiency virus (HIV); 13. Poorly controlled or severe cardiovascular and cerebrovascular diseases: congestive heart failure (NYHA standard III or level IV), severe arrhythmia requiring treatment or intervention, and poorly controlled hypertension after full treatment (systolic pressure >=160mmHg, diastolic pressure >=100mmHg ); 14. Pregnant or lactating female subjects; 15. The data analysis results of tumor tissue sequencing show that there are not enough new antigens available for vaccine preparation or vaccine preparation fails; 16. The researcher judges that the subject may not be able to continue to participate in the study: (1) Any other disease in which the subject faces the risk of safety; (2) Subjects with poor compliance or active request to withdraw from pre-screening; (3)There is a recurrence of the disease during the pre-screening period. Screening period 1. Postoperative complications have not recovered, or the complications are higher than the Clavien-Dindo complication grade 2; 2. The toxicity caused by auxiliary treatment before the first vaccine administration has not recovered to the baseline level or >1 (except for hair loss and pigmentation), and the neurotoxicity is >2; 3. There is evidence of active tuberculosis infection during the screening period, whether it is treated or not; 4. Chest CT during the screening period suggests evidence of interstitial pneumonia; 5. Concurrent severe infection within 28 days before the fir
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerance of RGL-270 monodrug and combined with adbelimab in patients at high risk of recurrence after radical treatment of malignant solid tumors; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK) characteristics of RGL-270 monodrug and combined with adbelimab;Immunogenicity of RGL-270 and/or immunogenicity of adebelimab;Preliminary efficacy of RGL-270 monotherapy and combined adebelimab in patients with high risk of recurrence after radical treatment of malignant solid tumors; | — |
Countries
China
Contacts
Public ContactXianjun Yu
Fudan University Shanghai Cancer Center
Outcome results
None listed