Solid tumors with FGFR
Conditions
Interventions
Part 1A: dose escalation group:Oral administration
Part 1B: dose expansion group:Oral administration
Part 2: dose expansion group:Oral administration
Sponsors
Zhejiang Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Subject must be voluntary to participate in this clinical trial and must sign the informed consent documents. 2. Age =18 years and =75 years. 3. Part 1A: Patients with locally advanced/metastatic solid tumor diagnosed histologically/cytologically, who have no standard treatment options or cannot tolerate standard treatment. Part 2A: Patients with locally advanced/metastatic solid tumor diagnosed histologically/cytologically (mainly including: gastric cancer, colon cancer, ovarian cancer, bile duct cancer, urothelial carcinoma, prostate cancer, hepatocellular carcinoma, etc.), who have no standard treatment options or cannot tolerate standard treatment. Patients have disease progression after previous treatment of immune checkpoint inhibitors, with tumor tissue or puncture specimen confirmed as PD-L1 positive by the accompanying diagnosis approved by FDA or NMPA. Part 1B/2B: Patients with locally advanced/metastatic solid tumors diagnosed histologically and/or cytologically (mainly including: gastric cancer, colon cancer, ovarian cancer, bile duct cancer, urothelial carcinoma, prostate cancer, hepatocellular carcinoma, etc.) who have no standard treatment options or cannot tolerate standard treatment. Confirmed FGFR aberrations in tumor tissue or biopsy samples. (See Appendix for specific definitions). 4. At least one measurable lesion (based on RECIST 1.1) (Part1B, Part 2). 5. ECOG score 0~1. 6. Predicted survival =3 months. 7. The functions of major organs are adequate, and the laboratory values during screening meet the following standards: Hematology: Absolute neutrophil count > 1.5×10^9/L Platelet count> 75×10^9/L Hemoglobin > 90g/L or > 5.6 mmol/L, no infusion of packed red blood cells (pRBC) in preceding 1 week, treatment with steady dose of erythropoietin (=3 months) is allowed. kidney: Serum creatinine 60 mL/min(for patients with creatinine levels = 1.5×ULN) Liver: Total bilirubin (serum) < 1.5×ULN unless know to have Gilbert syndrome, or total bilirubin =1.5×ULN with Child-Pugh score =7 (only for patients with liver tumors or liver metastasized tumors). AST and ALT < 2.5×ULN or =5×ULN(for patients with liver tumors or liver metastases) Blood coagulation: International Normalized Ratio (INR) or prothrombin time (PT) < 1.5×ULN, unless the patient is taking anticoagulant therapy. 8. Female patients (if of child bearing potential) at Screening must have negative pregnancy test within 7 days before administration. 9. Subjects must agrees to use reliable contraceptive methods from signing the informed consent until 90 days after the final dose. These include, but are not limited to: abstinence from sex, vasectomies for men, sterilization for women, effective Iuds, and effective contraceptive drugs. Note: Women of non-reproductive age include those who are permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) and those who have gone through menopause. Women =50 years of age were considered postmenopausal if they had ceased menstruation 12 months prior to the scheduled randomization date and had no other medical cause. Women < 50 years of age are considered postmenopausal if they have ceased menstruation for 12 months or more since the cessation of exogenous hormone therapy and their FSH levels are in the postmenopausal range.
Exclusion criteria
Exclusion criteria: 1. Received biological therapy, immunotherapy or other investigational drugs within 28 days before enrollment; Received chemotherapy or other targeted therapies within 14 days or 5 half-lives prior to enrollment (whichever is shorter). 2. Patients with central nervous system metastases who: a. require local treatment (surgery, radiation etc.) (Subjects with asymptomatic brain metastases, or symptomatic metastases which in the view of investigator do not require local treatment may be included); b. taking treatment with steroids over 10 mg prednisone per day (or equivalent); c. Continuous use of antiepileptic medication. 3. Patients with imaging (CT or MRI) showing tumor invasion of large blood vessels (such as aorta, pulmonary artery/vein, vena cava, etc.) or patients with potential bleeding risk. 4. Has a history of severe cardiovascular disease, including but not limited to: a. Severe cardiac rhythm or conduction abnormalities that require clinical intervention, such as ventricular arrhythmia, degree ?-? atrioventricular block, etc.; b. Acute coronary syndrome, congestive heart failure, stroke, or other grade 3 or higher cardiovascular events occurring within 6 months prior to first administration; c. Grade =II cardiac function according to New York Heart Association (NYHA) or left ventricular ejection fraction (LVEF) 450 ms for male or > 470 ms for female; f. Abnormity of blood potassium, blood magnesium or blood calcium at Screening. 5. Active infections requiring systemic intravenous anti-infective treatment, other than prophylactic antibiotics. 6. Has dysphagia or has acute gastrointestinal disorder that impacts drug absorption (such as Crohn's disease, ulcerative colitis, or short bowel syndrome) or other malabsorption conditions. 7. A known history of pulmonary interstitial disease, pulmonary fibrosis, or pneumonia due to tyrosine kinase inhibitors; pneumonia due to radiation therapy may be enrolled. 8. Previous or current endocrine diseases affecting calcium and phosphorus metabolism; The product of calcium and phosphorus > 50 mg2/dL2 (calcium: 1 mg/dl=0.25 mmol/L, that is, 1 mmol/L=4 mg/dl; Phosphorus: 1 mg/dl=0.3229 mmol/L, that is, 1 mmol/L=3.1 mg/dl); Previously known ectopic calcification of soft tissues (including but not limited to soft tissues, kidneys, intestines, lungs, etc., but not including cardiovascular, ligaments, lymph nodes, etc.). Medical history of clinically significant thyroid abnormalities, and thyroid function cannot recover and maintain in normal range under drug therapy. 9. Has a history of retinal vein obstruction (RVO) or central serous retinopathy (CSR), retinal pigment epithelial detachment (RPED), or has susceptibility factors of RVO, CSR or RPED (such as uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension, diabetes, elevated serum cholesterol, hypertriglyceridemia, Hypervisemia/ hypercoagulable syndrome, optic disc depression, intraocular pressure >21 mmHg, etc.). 10. Has medical history of corneal lesions, has following lesions confirmed by ophthalmic examination at Screening, including bu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| DLT incidence in each dose level (during the DLT observation), Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) of FH-2001; | — |
Secondary
| Measure | Time frame |
|---|---|
| The pharmacokinetics of FH-2001 after single or multiple doses, including AUC, Cmax, Tmax, CL/F, Vz/F, t1/2, Rac etc.;The frequency and severity of AE, SAE and abnormal safety findings (such as laboratory tests, vital signs, physical examination, electrocardiogram, ophthalmic examination etc.); The proportion of patients with dose adjustment or discontinuation due to drug toxicity;;ORR, DCR, DOR, PFS, OS; | — |
Countries
China
Contacts
Public ContactXiangdong Cheng
Zhejiang Cancer Hospital
Outcome results
None listed