Advanced Solid Tumors with SMARCA4 Protein Deficiency
Conditions
Interventions
Experimental Group:Dalpiciclib combined with Adebrelimab
Sponsors
Chongqing University Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1.Voluntarily participate in this study and sign the informed consent form; 2.Aged 18 to 75 years, male or female; 3.Histologically or cytologically confirmed advanced solid tumor with SMARCA4 protein deficiency confirmed by immunohistochemistry; 4.No other actionable mutations with corresponding targeted therapy available (including EGFR, ALK, ROS1, RET, c-Met, HER2, BRAF, etc.; patients with co-mutations may be enrolled after disease progression on targeted therapy); 5.Disease progression after at least one line of standard systemic therapy and no prior treatment with a CDK4/6 inhibitor; 6.At least one measurable lesion according to RECIST v1.1; 7.ECOG performance status 0–1; 8.Life expectancy > 3 months; 9.Adequate organ and bone marrow function: (1) Hematology: a) Hemoglobin (HGB) >= 90 g/L; b) Absolute neutrophil count (ANC) >= 1.5 × 10^9/L; c) Platelet count (PLT) >= 100 × 10^9/L; (2) Blood biochemistry: a) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 45 mL/min (Cockcroft-Gault formula); d) APTT <=1.5 × ULN and INR or PT <= 1.5 × ULN (in patients not receiving anticoagulation); 10.Female patients of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to enrollment and agree to use adequate contraception during the study and for 8 weeks after the last dose of study treatment; male patients must be surgically sterile or agree to use adequate contraception during the study and for 8 weeks after the last dose; 11.Willing and able to comply with follow-up until death, study completion, or study termination.
Exclusion criteria
Exclusion criteria: 1.Presence of actionable mutations or co-mutations with available targeted therapies (including EGFR, ALK, ROS1, RET, c-Met, HER2, BRAF, etc.); 2.Use of systemic corticosteroids or other immunosuppressive agents within 14 days prior to the first dose of study treatment, excluding nasal or inhaled corticosteroids or physiologic doses of systemic corticosteroids (i.e., =10 mg/day prednisone or equivalent); 3.Receipt of anti-tumor vaccines, traditional Chinese herbal medicines with anti-tumor indications, or systemic therapies with immunomodulatory effects within 4 weeks prior to the first dose; 4.History of other malignancies within 5 years prior to enrollment, except for carcinoma in situ that has been completely treated with no anticipated need for further therapy during the study period; 5.Current participation in an interventional clinical study, or receipt of another investigational drug or device within 4 weeks prior to the first dose, or planned receipt of a live attenuated vaccine within 4 weeks prior to the first dose or during the study; 6.Severe, localized, or active infection within 4 weeks prior to the first dose; 7.Active pulmonary tuberculosis infection within 1 year prior to the first dose; 8.HBsAg positivity with HBV DNA above the upper limit of normal (1000 copies/mL or 500 IU/mL), HCV positivity (acute or chronic infection indicated by HCV RNA or HCV antibody testing), active hepatitis B or C, known HIV positivity, or known AIDS; 9.Major surgical procedure within 4 weeks prior to the first dose, non-thoracic radiotherapy >30 Gy within 4 weeks prior to the first dose, or palliative radiotherapy <30 Gy within 4 weeks prior to the first dose; 10.Failure to recover adequately (i.e., to <= grade 1 or to baseline, excluding fatigue or alopecia) from toxicities and/or complications of any prior intervention before the first dose; 11.Grade II or higher myocardial ischemia or myocardial infarction, poorly controlled arrhythmias, history of significant hemorrhagic events, arterial/venous thrombosis, pulmonary embolism, or risk of gastrointestinal perforation; 12.Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage; 13.History of interstitial lung disease (e.g., idiopathic pulmonary fibrosis, organizing pneumonia [such as bronchiolitis obliterans], drug-induced pneumonitis, radiation pneumonitis requiring steroid therapy), or suspected interstitial lung disease on screening imaging that cannot be ruled out (subjects with radiation fibrosis confined to the radiation field who do not require steroid therapy are eligible), or presence of respiratory failure, severe asthma, severe chronic obstructive pulmonary disease, or other pulmonary conditions significantly affecting lung function; 14.Any condition that, in the investigator’s opinion, may compromise the subject’s safety or interfere with the subject’s ability to comply with or complete the study requirements.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose, MTD;Objective response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression-free survival period;Disease control rate;Overall survival period; | — |
Countries
China
Contacts
Public ContactLi Yongsheng
Chongqing University Cancer Hospital
Outcome results
None listed