Deletion Mutations in the SWI/SNF Complex
Conditions
Interventions
Two-drug combination group:Chidamide+ Anlotinib
Three-drug combination group:Chidamide+ Anlotinib + PD-1/PD-L1 inhibitors
Sponsors
Cancer Hospital Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: (1) Aged 18 to 80, male or female. (2) Patients with histologically or cytologically confirmed unresectable advanced or metastatic solid tumors. (3) Patients with deletion mutations in SWI/SNF complex subunit genes (SMARCA1, SMARCA2, SMARCA4, SMARCB1, SMARCC2, SMARCC1, SMARCF1/ARID1A), or negative immunohistochemical results for related proteins (SNF2L, BRM, BRG1, BAF47, BAF170, BAF155, BAF250a). (4) Standard treatment failure or intolerance to standard treatment. (5) ECOG performance status of 0-2. (6) Must have at least one measurable target lesion defined by RECIST v.1.1. (7) Must have adequate organ and bone marrow function: Blood tests: Absolute neutrophil count (ANC) = 1.5 × 10^9/L; platelet count (PLT) = 80 × 10^9/L; hemoglobin (HGB) = 90 g/L. Liver function: Serum total bilirubin (TBIL) = 1.5 × upper limit of normal (ULN); for patients without liver metastases, ALT and AST = 3.0 × ULN; for those with liver metastases, ALT and AST = 5.0 × ULN; serum albumin = 25 g/L. Kidney function: Serum creatinine (Cr) = 1.5 × ULN. Urinalysis showing urine protein < 2+; patients with baseline urinalysis showing urine protein = 2+ should undergo 24-hour urine collection, and total 24-hour urine protein should be < 1 g. Coagulation function: International normalized ratio (INR) = 1.5 × ULN, and activated partial thromboplastin time (APTT) = 1.5 × ULN. (8) Must voluntarily sign an informed consent form (ICF). (9) Expected survival time of = 3 months. (10) Female subjects of childbearing age or male subjects with female partners of childbearing age must use effective contraception throughout the treatment period and for 6 months after treatment.
Exclusion criteria
Exclusion criteria: (1) Previously used HDAC inhibitors or anlotinib. (2) Received any anticancer treatments or investigational drugs and devices within 28 days prior to the first administration of the study treatment. (3) Received radiation therapy within 2 weeks prior to the first dose of the study treatment or received >30 Gy of chest radiation within the past 6 months. (4) Patients with uncontrolled hypertension (systolic blood pressure =150 mmHg or diastolic blood pressure =100 mmHg) despite standard treatment measures. (5) Received systemic immunosuppressive drugs within 28 days prior to the first administration of the study treatment. Inhaled or topical steroids and physiological doses of systemic corticosteroids (=10 mg/day of prednisone equivalent) are allowed. (6) Received systemic immunostimulatory drugs within 28 days prior to the first administration of the study treatment. (7) Had vaccination with live vaccines within 28 days prior to the first dose of the study treatment or plan to be vaccinated during the study. Note: Injectable seasonal influenza vaccines are usually inactivated influenza vaccines and are permitted; COVID-19 vaccines are also allowed. (8) Underwent major surgery within 28 days prior to the first administration of the study treatment. (9) Has not recovered from adverse reactions caused by prior antitumor treatment (= Grade 2 as defined by CTCAE v5.0). (10) Symptomatic and untreated central nervous system metastasis. (11) Uncontrollable pleural/abdominal/pericardial effusion occurring within 1 month prior to the first administration of the study treatment. (12) Uncontrolled or significant cardiovascular or cerebrovascular diseases. (13) A history of hemoptysis within 2 weeks prior to the first administration of the study treatment or a history of active bleeding within 2 months; or subjects who are on anticoagulants, or have a significant high-risk of bleeding tendency during screening. (14) A history of serious thromboembolic events within 6 months prior to the first administration of the study treatment. (15) Suspected interstitial lung disease or pulmonary fibrosis, or pulmonary inflammation requiring treatment; or a history of pulmonary disease treated with oral or intravenous steroids within 6 months prior to the first administration of the study treatment. (16) Significant gastrointestinal abnormalities during screening that may affect the intake, transport, or absorption of the drug. (17) Urine protein =2+ and quantitative urine protein =1 g/24 h during screening. (18) Active infection requiring intravenous treatment; or severe infection occurring within 28 days prior to the first administration of the study treatment. (19) Known active tuberculosis, or currently undergoing anti-tuberculosis treatment, or having received anti-tuberculosis treatment within 1 year prior to the first administration of the study treatment. (20) Known to have acute or chronic active hepatitis B (HBsAg positive and HBV DNA =500 IU/mL or =10^3 copies/mL) or acute or chronic active hepatitis C (HCV antibody positive and HCV RNA positive). (21) HIV positive or with a history of AIDS or other serious infectious diseases. (22) History of other primary malignant tumors, excluding malignant tumors that have been completely relieved for at least 2 years before enrollment and do not require any other treatment during the study period; Non melanoma skin cancer or malignant freckle nevi that have been adequately treated and have no evidence of disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 12 week progression-free survival rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| overall response rate;progression-free survival;overall survival;Duration of Response; | — |
Countries
China
Contacts
Public ContactYutao Liu
Cancer Hospital Chinese Academy of Medical Sciences
Outcome results
None listed