Phase Ib/II Study of Fluzoparib in Combination With Dalpiciclib in Patients With Locally Advanced or Metastatic Sarcoma

Inclusion Criteria:1.Patients aged 12 to 75 years, male and female ; 2.Eastern CooperativeOncology Group ( ECOG ) physical status score was 0-2 ; 3.Locally advanced or metastaticsarcomas ( including osteosarcoma, Ewing sarcoma, undifferentiated sarcoma, liposarcoma,leiomyosarcoma, fibrosarcoma and synovial sarcoma ) confirmed by histopathology, and atleast one measurable lesion without local treatment ( according to RECIST v1.1, the longdiameter of the measurable lesion mesured by spiral CT scan should be≥ 10 mm or the shortdiameter of the lymph node lesion should be ≥ 15 mm ) ; 4.Life expectancy≥ 12 weeks ; 5.Themain organ function is basically normal and meets the program requirements : a)Blood examination : (without blood transfusion within 14 days before screening, withoutusing granulocyte colony stimulating factor [ G-CSF ], or other methods to correct bonemarrow suppression within 7 days ) ,Blood indicators should meet: i.hemoglobin ≥ 90 g / L ;ii.neutrophil count ≥ 1.5 × 109 / L ; iii.Platelet count ≥ 75 × 109 / L ; b)b. Biochemicalexamination : ( no albumin transfusion within 14 days ) indicators should meet: i.albumin ≥ 29 g / L ; ii.Alanine aminotransferase ( ALT ) and aspartate aminotransferase ( AST ) ≤ 2.5times the upper limit of normal ( ULN ) ; iii.total bilirubin ( TBIL ) ≤ 1.5 times ULN ;iv.Creatinine Cr ≤ 1.5 times ULN or Cr clearance > 50 mL / min; v.Urine protein < 2 +. IfUrine protein ≥ 2 +, an 24 hours ( h ) urine protein quantification test should be taken,and 24h urine protein quantification < 1.0 g is allowed to include ) ; c)Coagulationfunction : activated partial thromboplastin time ( APTT ) and international normalizedratio ( INR ) ≤ 1.5 × ULN ( for those who regularly use anticoagulant therapy such as lowmolecular weight heparin or warfarin and INR meets the expected requirement are allowed toinclude ) ; d)Thyroid stimulating hormone ( TSH ) ≤ ULN ; If not, T3 and T4 levels shouldbe examined, and only with normal T3 and T4 level is allowed to include. e)Echocardiography : left ventricular ejection fraction ( LVEF ) ≥ 60 %. 6.Non-surgicalsterilization or women of childbearing age who are required to use a medically approvedcontraceptive (such as an intrauterine device, contraceptive pill or condom) during thestudy treatment period and for 6 months after the study treatment period ends; Femalepatients of childbearing age who were not surgically sterilized must have a negative serumor urine HCG test within 7 days prior to study enrollment; And must be non-lactationperiod; For male patients with a partner of a woman of childbearing age, effectivecontraceptive methods should be used during the trial period and within 6 months after thelast Fluzoparib or Dalpiciclib administration. Understand the research procedures and methods, volunteer to participate in the experiment,and sign the informed consent. And fully understand the trial content, process and possibleadverse reactions.

Exclusion Criteria:1.Plan to receive any other antitumor therapy during this trial; 2.Within 4 weeks of the first administration of the drug in this study, the patient hasreceived radiotherapy for sarcoma, or received compound names such as Fluzoparib,Dalpiciclib, drug administration or cell therapy in other clinical trials; 3.Imagingdiagnosis showed the presence of tumor lesions in the brain; 4.Active malignancies otherthan sarcoma within 5 years or at the same time. Cured localized tumors, such as skin basalcell carcinoma, skin squamous cell carcinoma, superficial bladder carcinoma, prostatecarcinoma in situ, cervical carcinoma in situ, breast carcinoma in situ, etc., could beincluded in the group.

5.Patients with clinical symptoms of ascites requiring puncture or drainage, or patientswho have received ascites drainage within the past 3 months, except those who only show asmall amount of ascites without clinical symptoms on imaging; Uncontrolled or medium orabove pleural effusion and pericardial effusion; There is evidence of abdominal gasaccumulation that cannot be explained by puncture or recent surgical procedures 6.Have ahistory of epilepsy, or a history of seizures within 12 months prior to the firstadministration of the study drug (including a history of transient ischemic attack,cerebral stroke (except imaging only found ischemic focus but no corresponding clinicalhistory), brain trauma with disturbance of consciousness requiring hospitalization); 7.Previous treatment with PARP or CDK4/6 inhibitors, including but not limited toFluzoparib and Dalpiciclib; 8.Allergic constitution, including severe drug allergy or drugallergic reaction history; Known allergies or intolerances to Fluzoparib, Dalpiciclib ortheir excipients; 9.Severe infections (CTC AE ≥grade 2), such as severe pneumonia,bacteremia, and infection complications requiring hospitalization, occurred within 4 weeksprior to the first use of the study drug; Baseline chest imaging suggests active pulmonaryinflammation, signs and symptoms of infection within 2 weeks prior to the first use of thestudy drug, or the need for oral or intravenous use of the drug · Antibiotic therapy (excluding the use of prophylactic antibiotics); 10.Drugs that may affect P-gp should notbe discontinued during the study； 11.Had use of a potent/moderate-acting drug that inhibitsor induces the liver drug metabolizing enzyme CYP3A4 14 days prior to initialadministration； 12.Inability to swallow, chronic diarrhea, intestinal obstruction, or otherfactors affecting drug administration and absorption; 13.A history of myelodysplasticsyndrome (MDS)/acute myeloid leukemia (AML), or other malignancies (other than carcinoma insitu with complete response and malignancies determined by the investigator to be slow inprogression) within 5 years prior to the initial administration of the study; 14.Combinedwith other viral infection (anti-HCV, anti-HIV positive, HBsAg positive) or syphilisinfection; 15.A history of immunodeficiency (including HIV test positive, other acquired orcongenital immunodeficiency diseases) or a history of organ transplantation; 16.A knownhistory of psychotropic drug abuse, alcoholism and drug use; A concomitant disease (such aspoorly controlled hypertension, severe diabetes, thyroid disease, and psychosis) or anyother condition that, in the investigator's judgment, seriously endangers the patient'ssafety or affects the patient's ability to complete the study.