advanced solid tumor
Conditions
Interventions
dose escalation:HG030 tablets
dose expansion:HG030 tablets
Sponsors
Beijing Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Inclusion criteria Each patient must meet all of the following inclusion criteria to be eligible for study entry. 1) All subjects or legal representatives must personally sign the informed consent form approved by the Ethics Committee before starting any screening procedure; 2) Male or female subjects aged 18 to 75 years (including the cut-off value), 3) Subjects with locally advanced or metastatic solid tumors who have progressed after standard treatment, or are not suitable or are intolerable to standard treatment, or refuse to receive standard treatment, or for whom no alternative effective standard therapy is available; 4) Subjects may provide archival tumor tissue samples or undergo fresh tumor sample biopsy. Phase 1a: NTRK gene or ROS1 gene alterations are not necessary for subject enrollment (patients who are unable to provide sufficient tumor tissue for molecular assays may be enrolled only after consultation with the sponsor and written consent has been obtained); Phase 1b: consisting of 3 expansion cohorts that meet 1 of the following conditions: ? NTRK gene fusion cohort: NTRK gene fusion identified at central laboratory; ? ROS1 gene fusion cohort: ROS1 gene fusion identified at central laboratory, and subjects have progressed standard treatment such as crizotinib or not suitable/intolerable or refused standard treatment; ? Other NTRK gene alterations cohorts: other NTRK gene alterations [such as gene copy number variation (CNV), point mutation, etc.] identified at central laboratory. 5) ECOG score of 0 to 1 (including 1); 6) Life expectancy of at least 3 months; 7) Subjects must have at least one measurable lesion as defined by RECIST 1.1 during the screening period. Subjects with primary CNS tumors must have at least site of bi-dimensionally measurable disease at screening (confirmed by magnetic resonance imaging [MRI] and evaluable by RANO criteria), with the size of at least one of the measurable lesions = 1 cm in each dimension and noted on more than one imaging slice; 8) Subjects should have adequate organ and bone marrow function and have not received recombinant granulocyte stimulating factor (long-acting granulocyte colony-stimulating factor required 2 weeks apart), erythropoietin, thrombopoietin receptor agonists, recombinant interleukin-11 and other hematopoietic promoting drugs and platelet and red blood cell transfusions within 7 days before screening; Hematological parameters: Absolute neutrophil count (ANC) = 1.5 × 10^9/L; Platelet count (PLT) = 100 × 10^9/L; Hemoglobin (Hb) = 90 g/L; Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) = 2.5 times the upper limit of normal (ULN), and for patients with liver cancer and/or liver metastases, ALT or AST = 5 times ULN; Total bilirubin = 1.5 times ULN (total bilirubin should be < 3 times ULN for subjects with Gilbert 's syndrome); creatinine clearance = 30 mL/min; international normalized ratio (INR) = 1.5 × ULN, activated partial thromboplastin time (APTT) = 1.5 × ULN; 9) Male or female subjects who meet any of the following conditions: Females of non-childbearing potential, defined as having had a hysterectomy, or bilateral oophorectomy, or bilateral tubal ligation or postmenopausal (= 1 year of amenorrhea); Females of childbearing potential who have a negative serum pregnancy test 7 days prior to enrollment and use effective contraception such as double-barrier contraception, condoms, oral or injectable contraceptives, intrauterine d
Exclusion criteria
Exclusion criteria: Exclusion criteria : 1) Prior treatment with other ROS1-TKI or TRK-TKI except Crizotinib, Entretinib, Loratinib, larotrectinib and Ensatinib, or participation in clinical trials (Phase Ib only); 2) Patients who received chemotherapy (for nitrosourea, Mitomycin C and liposomal doxorubicin, within 6 weeks before the first study drug treatment), radiotherapy, small molecule targeted therapy, immunotherapy and antibody-directed therapy within 2 weeks prior to planned start of HG030 or 5 half-lives; 3) Adverse events (except alopecia) due to previous treatments did not resolve or do not recover to grade 0 or 1 (CTCAE 5.0) before the first study drug treatment; 4) Surgery within 4 weeks before the study treatment, and those who have not yet recovered, but the investigator judged that minor surgery (e.g., tooth extraction, etc.) and diagnostic surgery did not affect participation in the trial; 5) Currently active second malignancy, except for adequately treated basal or squamous cell skin cancer and/or Cervical carcinoma in situ and/or limited stage prostate cancer and/or superficial bladder cancer. Patients with other cancers must have been disease-free for 5 years or more; 6) Patients with primary, metastatic central nervous system tumors, with the following exceptions: asymptomatic on stable doses of steroids [= 4 mg/day dexamethasone or equivalent doses of other hormones] for maintenance or dose reduction for more than 2 weeks, or not requiring steroid therapy; 7) Clinically significant cardiac, cerebral, and vascular abnormalities: e.g., heart failure (Class = 2, New York Heart Association (NYHA)), left ventricular ejection fraction (LVEF) 220 msec; 8) During screen, abnormal results of corrected QT interval (Fridericia formula corrected QT interval, QTcF) at rest: those with abnormal results in the first test should be retested for 3 times, mean QTcF from all 3 ECGs > 440 msec; 9) known factors that may increase the risk of QTc prolongation or arrhythmia events: hypokalemia, long QT syndrome (LQTS), family history of first-degree relatives with LQTS or sudden unexplained death at age 10.0 mmol/L); 13) active bleeding constitution; Active uncontrolle
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The incidence and category of dose limiting toxicity (DLTs); | — |
Secondary
| Measure | Time frame |
|---|---|
| PK parameters;Objective response rate (ORR), disease control rate (DCR), duration of response (DOR), Progression-free survival (PFS);OS; | — |
Countries
China
Contacts
Public ContactLin Shen
Beijing Cancer Hospital
Outcome results
None listed