Pregnancy or lactation.21. solid tumours who failed standard treatment; the study aims to evaluate the safety and efficacy of targeted drugs in patients with advanced rare solid tumours with corresponding actionable alterations, as well as the safety and efficacy OAC1 of immune checkpoint (programmed death receptor inhibitor 1, PD-1) inhibitors in patients with advanced rare solid tumours without actionable alterations. Patients with advanced rare tumours who fail standardised treatment and carry actionable alterations (Epidermal growth factor receptor (EGFR) mutations, ALK gene fusions, ROS-1 gene fusions, Alas2 C-MET gene amplifications/mutations, BRAF mutations, CDKN2A mutations, BRCA1/2 mutations, HER-2 mutations/overexpressions/amplifications or C-KIT mutations) will be enrolled in the targeted therapy arm and be given the corresponding targeted drugs. Patients without actionable alterations will be enrolled in the PD-1 inhibitor arm and be treated with sintilimab. After the patients treated with vemurafenib, niraparib and palbociclib acquire resistance, they will receive combination treatment with sintilimab or atezolizumab. With the use of Simons two-stage Minimax design, and the sample size was estimated to be 770. The primary endpoint of this study is the objective response rate. The secondary endpoints are progression-free survival in the targeted treatment group and single-agent immunotherapy group; the duration of response in the targeted therapy and single-agent immunotherapy groups; durable clinical benefit in the single-agent immunotherapy group; and the incidence of adverse events. Ethics and dissemination Ethics approval was obtained from the Chinese Academy of Medical Sciences (ID: 20/132-2328). The results from this study will OAC1 be actively disseminated through manuscript publications and conference presentations. Trial registration numbers “type”:”clinical-trial”,”attrs”:”text”:”NCT04423185″,”term_id”:”NCT04423185″NCT04423185; ChiCTR2000039310. antibody positivity. 14. Signed, written informed consent obtained from volunteers who join the study to follow the study treatment plan and the follow-up visit plan and to cooperate in observing the treatment adverse events and efficacy.14. Current evidence of uncontrollable systemic diseases (such as severe mental or neurological disease; epilepsy or dementia; unstable or uncompensated respiratory, cardiovascular, liver or kidney diseases; uncontrolled hypertension (ie, still greater than or equal to CTCAE level three hypertension after drug treatment)).15. A history of myocardial infarction, coronary artery/peripheral artery bypass or cerebrovascular accident within 3 months.16. A history of other malignancy within the last 5 years, except for cured carcinoma in situ.17. A history of undergoing any organ transplantation, including allogeneic stem cell transplantation. Transplantations without immunosuppression (corneal transplantation, hair transplantation) are not included in this criterion. Cardiovascular disease or symptom, including any of the following: A history of congestive heart failure requiring treatment and of OAC1 New York Heart Association class III/IV CHF. Current ventricular arrhythmia requiring antiarrhythmic drug treatment or uncontrollable or unstable arrhythmia. Severe conduction disorder (such as grade II or III AV block). Angina requiring treatment. QT interval (QTC) of 12-lead ECG is 450 ms in males and 470 ms in females. A history of congenital long QT syndrome, congenital short QT syndrome, torsade de pointe or pre-excitation syndrome. A history of LVEF decline to below 50%, as determined by echocardiography or MUGA scan. A history of myocardial infarction in the past 6 months. Inadequate bone marrow reserve or organ function, as evidenced by the following laboratory results: Absolute value of neutrophils 1.5109/L. Platelet count 100 109/L (transfusion-dependent patients should be excluded from this study). Haemoglobin 90 g/L. ALT 2.5 x the upper limit of normal (ULN) if there are no clear liver metastases or ALT 5 x ULN if there are liver metastases. Aspartate aminotransferase (AST) 2.5 x ULN if there are no definite liver metastases or AST 5 x ULN if there are liver metastases. Total bilirubin 1.5 x ULN if there are no liver metastases or total bilirubin 3 x ULN if there is definite Gilbert syndrome (unconjugated hyperbilirubinaemia) or liver metastases. Creatinine 1.5 x ULN with creatinine clearance 50 mL/min (measured value, or calculated value by the Cockcroft-Gault formula; only when creatinine 1.5 x ULN does creatinine clearance need to be checked for confirmation). If bone metastasis is present and investigator concludes that liver function is adequate, the increase in ALP alone will not be reason for study exclusion. International normalised ratio and activated partial thromboplastin time or partial thromboplastin time (PTT or PTT) 1.5.