Non-squamous NSCLC with EGFR TKIs resistant and brain metastases.
Conditions
Interventions
Experimental Group:AK112 combined with chemotherapy and brain radiotherapy
Sponsors
Sichuan Cancer Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following criteria to be eligible for this trial: (1) Diagnosed with stage IV NSCLC, combined with EGFR gene mutation, and having failed previous EGFR-TKIS treatment; (2) Enhanced MRI diagnosis of brain metastases, with or without meningeal metastases; (3) The brain metastases intended for radiotherapy have not received local radiotherapy before; (4) There are no contraindications for brain radiotherapy; (5) Age: no less than 18 years old and no more than 75 years old, gender not limited. (6) The ECOG PS score is 0 or 1 point; (7) There are measurable and/or unmeasurable lesions that conform to the definition of RECIST v1.1; (8) The functions of important organs meet the following requirements (no blood components or cell growth factors are allowed to be used two weeks before the start of the study and treatment) : The blood routine test must meet: Absolute neutrophil count (ANC) >=1.5×10^9/L; Hemoglobin (HB) >=9g/dL; Platelet count (PLT) >=100×10^9/L; Serum albumin (ALB) >=2.8g/dL; White blood cell (WBC) >=4.0×10^9/L. Biochemical tests must comply with: Total bilirubin (TBIL) =50ml/min (Cockcroft-Gault formula); Blood urea nitrogen (BUN) is within the normal range. Normal thyroid function: T4 serum thyroxine: 65-155nmol/L(5.0-12.0µg/dL); FT4 serum free thyroxine: 10.3-31.0pmol/L(0.8-2.3ng/dL); T3 Serum triiodothymidine: 1.8-2.9nmol/L(115-190ng/dL); FT3 serum free triiodothyronine: 2.0-6.6pmol/L; TSH (Serum thyroid Stimulating Hormone) : 0.3-5.0mU/L; (9) Expected survival period > 6 months; (10) The researchers determined that the patient could receive bispecific antibody treatment. (11) The patient has no autoimmune diseases. (12) Female subjects with fertility should undergo a urine or serum pregnancy test within 72 hours before the first administration of the study drug, and the test results should be negative. They should also be willing to use effective contraceptive methods from the trial period until 3 months after the last administration of toripalimab. For male subjects whose partners are women of childbearing age, effective contraceptive methods should be adopted during the trial period and within 3 months after the last administration of therapeutic drugs. (13) The patients voluntarily joined this study, signed the informed Consent Form (ICF), had good compliance and cooperated with the follow-up.
Exclusion criteria
Exclusion criteria: Cancer-specific exclusion criteria: (1) Combined with severe symptoms of the central nervous system; (2) Brain metastases intended for brain radiotherapy or the whole brain has received local radiotherapy; (3) Brain metastases require surgery; (4) Unable to undergo brain MRI examination; (5) Uncontrolled tumor-related pain; (6) According to the researcher's judgment, there is evidence of serious or uncontrollable systemic diseases (such as unstable or non-compensatory respiratory, heart, liver or kidney diseases); (7) Uncontrolled pleural effusion, pericardial effusion, or ascites that requires repeated drainage (once a month or more frequently); Allow patients to have indwelling catheters (such as PleurX®); (8) Uncontrollable or symptomatic hypercalcemia (>1.5 mmol/L ionic calcium or calcium >12 mg/dL or corrected serum calcium >ULN); (9) Randomly assign a history of malignant tumors other than lung cancer within the previous 5 years, but with negligible risk of metastasis or death [e.g., expected 5-year overall survival rate >90%], and excluding malignant tumors that are expected to be cured after treatment, such as appropriately treated cervical carcinoma in situ, basal or squamous cell skin cancer, and localized prostate cancer that has undergone radical surgery And ductal carcinoma in situ treated by radical surgery; (10) Bone metastases in multiple segments of the vertebral body, ilium, etc., which are prone to cause fractures and pose a risk of paraplegia, affect subsequent follow-up. (11) A single liver metastatic lesion is larger than 5cm or the load of the liver metastatic lesion accounts for more than 50% of the total liver volume; (12) Patients who are known to have complete obstruction under endoscopy and require interventional treatment or surgical treatment to relieve the obstruction. Subjects who meet any of the following criteria will be excluded from this trial: (1) After stent implantation in the esophageal or tracheal cavity; (2) Has received treatment with VEGF-A targeted drugs, programmed cell death protein-1 (PD-1), PD-L1 or programmed cell death ligand-2 (PD-L2) drugs, or other tumor immunotherapies; (3) Patients with a high risk of bleeding or perforation due to significant tumor invasion of adjacent organs (large arteries or trachea) of esophageal lesions, or those who have already developed fistulas; (4) Those with severe malnutrition (PG-SGA>=9 points) and whose nutritional status still cannot be corrected after 1 to 2 weeks of active nutritional treatment; (5) Those who are known or suspected of being allergic to bispecific antibodies, pemetrexed, or carboplatin components; (6) Those who already have or have concurrent hemorrhagic diseases; (7) Pregnant and lactating patients; (8) Those who fail to give informed consent due to psychological, family, social or other factors; (9) Patients with severe heart, lung, liver or kidney insufficiency, hematopoietic system diseases, immune system diseases, cachexia, etc. (10) There is an active infection or an unexplained fever > 38.5? during the screening period or before the first administration (as determined by the researcher, the subjects with fever caused by tumors can be enrolled); (11) Suffering from congenital or acquired immune deficiency (such as HIV-infected individuals), active hepatitis B (HBV-DNA>=104 copies /mL), or hepatitis C (positive hepatitis C antibody, and HCV-RNA higher than the detection limit of the analytical method); (12) The subject is part
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety; | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy; | — |
Countries
China
Contacts
Public ContactWang Qifeng
Sichuan Cancer Hospital
Outcome results
None listed