Advanced/Metastatic Solid Tumors
Conditions
Interventions
10mg group:XZP-7797-H1
20mg group:XZP-7797-H1
40mg group:XZP-7797-H1
80mg group:XZP-7797-H1
120mg group:XZP-7797-H1
160mg group:XZP-7797-H1
200mg group:XZP-7797-H1
240mg group:XZP-7797-H1
Sponsors
Beijing Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Aged between 18 and 75 years; 2. Histologically or cytologically confirmed unresectable locally advanced or metastatic solid tumours (predominantly advanced breast and ovarian cancers), meeting any of the following criteria: a) Progression or recurrence following standard therapy; b) No standard therapy available for the current disease stage; c) Inability to tolerate standard therapy or inaccessibility to standard therapy; 3. For ovarian cancer subjects with prior platinum-based therapy, sensitivity to platinum-based treatment is required; 4. Subjects with pathogenic or likely pathogenic somatic or germline BRCA1/2 mutations, HRD positivity, or HRR gene mutations; 5. Performance status (ECOG score) of 0–1; 6. Subjects must have at least one evaluable lesion meeting RECIST v1.1 criteria; 7. All acute toxicities from prior antineoplastic therapy or surgical complications/sequelae must have resolved to = Grade 1 (NCI-CTCAE v5.0), excluding alopecia or other toxicities deemed by the investigator to pose no safety risk to the subject; 8. All prior antineoplastic therapy must have been discontinued for at least 4 weeks prior to the first administration of XZP-7797-H1 tablets (with nitrosoureas or mitomycin discontinuation =6 weeks, and endocrine therapy, oral small-molecule targeted therapies, and traditional Chinese medicine [including decoctions or proprietary Chinese medicines] discontinued for at least 2 weeks); 9. The subject's expected survival period is =12 weeks; 10. The subject has good organ function at baseline examination, with laboratory test results meeting the following criteria: a) Complete blood count: Absolute neutrophil count (ANC) = 1.5 × 10^9/L, white blood cell count (WBC) = 3.0 × 10^9/L, platelet count (PLT) = 90 × 10^9/L, haemoglobin (HGB) = 100 g/L; b) Liver function: Serum total bilirubin (TBIL) = 1.5 × upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 × ULN; c) Renal function: Creatinine clearance (CrCl) = 50 mL/min (calculated using the Cockcroft-Gault formula); d) Coagulation function: Prothrombin time (PT) = 1.5 × ULN, International Normalised Ratio (INR) = 1.5 × ULN or Activated Partial Thromboplastin Time (APTT) = 1.5 × ULN; 11. Male or female subjects of reproductive potential must agree to use effective contraception during the study period and for 6 months after the last study dose, such as dual barrier contraception, condoms, oral or injectable contraceptives, intrauterine devices, etc.; 12. Subjects must have fully understood and voluntarily signed the informed consent form, and be able and willing to comply with the study protocol requirements for visits, treatment plans, laboratory tests, and other study procedures.
Exclusion criteria
Exclusion criteria: 1. Previous treatment with PARP inhibitors; 2. Presence of meningeal metastases or symptomatic central nervous system metastases; however, subjects with previously treated brain metastases may be enrolled if disease has been stable for over 4 weeks without intervention and the brain metastases are asymptomatic; 3. Uncontrolled malignant pleural/ascites/peritoneal effusion and/or pericardial effusion; 4. Diagnosis of any other malignancy within 3 years prior to enrolment, except basal cell carcinoma, cutaneous squamous cell carcinoma, or cervical carcinoma in situ that has been adequately treated and is stable; 5. History of haematopoietic stem cell or bone marrow transplantation; 6. Major surgery for any reason within 4 weeks prior to enrolment, or unresolved postoperative complications at the time of dosing; 7. Active hepatitis B: HBsAg-positive and/or HBcAb-positive with HBV-DNA > 500 IU/mL; active hepatitis C: HCV antibody-positive subjects may only be enrolled if HCV-RNA is negative by PCR; 8. Concurrent human immunodeficiency virus (HIV) infection; 9. Fever exceeding 37.5°C or clinically evident active infection likely to affect the trial, including active pulmonary tuberculosis; 10. Uncontrolled electrolyte disturbances (e.g., hyponatraemia, hypokalaemia); 11. History of cerebrovascular accident within 6 months prior to enrolment, including transient ischaemic attack or stroke; 12. History of extensive diffuse/bilateral pulmonary interstitial fibrosis, or known grade 3 or 4 pulmonary interstitial fibrosis, or current clinically significant active pulmonary disease; 13. Cardiac impairment or clinically significant cardiac disease, including but not limited to any of the following: a) History of long QT syndrome or confirmed familial predisposition to long QT syndrome; b) Anticipated use of QT-prolonging concomitant medications during the trial; c) History of clinically significant ventricular arrhythmias; d) History within 6 months prior to enrolment of unstable angina pectoris, acute myocardial infarction, coronary artery bypass graft surgery, or symptomatic congestive heart failure; e) Current implantation of a defibrillator or pacemaker for the treatment of ventricular arrhythmias; f) Baseline QTcF interval >450 msec (males) and >470 msec (females) as calculated using the Fridericia formula; g) Complete left bundle branch block or complete right bundle branch block with left anterior fascicular block (double bundle branch block); h) Echocardiography demonstrating LVEF <50%; 14. Diseases judged by the investigator to potentially significantly impair gastrointestinal absorption, and/or prior surgical procedures affecting absorption; 15. Presence of any serious and/or uncontrolled concomitant disease judged by the investigator to potentially interfere with study assessment; 16. Subjects currently receiving medications known to strongly inhibit or induce CYP3A, which cannot be discontinued within 2 weeks prior to dosing (or within 5 half-lives of the drug, whichever is longer) and throughout the study period; 17. Subjects scheduled for surgery, or deemed by the investigator to require surgical intervention; 18. Participation in any other interventional clinical trial within one month prior to enrolment (excluding subjects who have completed other clinical studies and are only undergoing follow-up survival monitoring); 19. Known history of allergy to any component of the study drug; 20. Subjects with known psychiatric disorders that
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Tolerated Dose (MTD);Recommended Phase II Dose (RP2D);Incidence of treatment emergent adverse events; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate;Disease control rate (DCR);Clinical benefit rate (CBR);Duration of response (DoR);Progression free survival (PFS);PK parameter; | — |
Countries
China
Contacts
Public ContactHuiping Li
Beijing Cancer Hospital
Outcome results
None listed