A Phase I Study of the Safety, Tolerability, Pharmacokinetics Profiles and Preliminary Efficacy of 3D185 Monotherapy in Subjects With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- Highly selective FGFR1-3 inhibitor
- Conditions
- Solid Tumor, Adult
- Sponsor
- 3D Medicines (Beijing) Co., Ltd.
- Enrollment
- 42
- Locations
- 2
- Primary Endpoint
- Safety Evaluation: frequency and severity of AEs
- Status
- Active, not recruiting
- Last Updated
- 11 months ago
Overview
Brief Summary
A Phase 1 Study of the Safety, Tolerability, Pharmacokinetics Profiles, and Preliminary Efficacy of 3D185 Monotherapy in Subjects with Advanced Solid Tumors
Detailed Description
Subjects with advanced solid tumors who have no available standard therapy or who have failed standard therapies. This is an open-label, global multicenter, dose-escalation phase 1 study of safety, tolerability, preliminary PK profile, and preliminary efficacy of 3D185 capsules monotherapy in subjects with advanced solid tumors. The starting dose in this dose-escalation study is 50 mg, and the preset 6 dose-escalation cohorts are 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, and 300 mg, respectively.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects must be male or female and ≥ 18 years of age on the day of enrollment.
- •Subjects must have a histological diagnosis of locally advanced or metastatic malignant solid tumors. Subjects must have failed or have been intolerant to established standard therapies, or standard therapies did not exist or were no longer effective for a given tumor type, or in the opinion of the Investigator have been considered ineligible for a particular form of standard therapy on medical grounds.
- •Subjects must have at least one evaluable lesion (according to RECIST 1.1, see Appendix 1);
- •ECOG Performance Status of 0 or
- •Life expectancy ≥ 12 weeks.
- •Subjects must have normal levels of total serum calcium and total phosphate.
- •Subjects must have adequate organ and bone marrow function (no hematopoietic growth factor, blood transfusion, or platelet therapy within 1 week before the first dose):
- •CBC: neutrophils ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L, hemoglobin ≥ 9.0 g/dL.
- •Liver function: total bilirubin ≤ 1.5 × ULN; ALT/AST ≤ 2.5 × ULN without liver metastasis; ALT/AST ≤ 5 × ULN with liver metastasis;
- •Coagulation: International normalized ratio (INR) ≤ 1.5 × ULN and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (for patients undergoing anticoagulant therapy. The Investigator will judge that the INR and APTT are within a safe and effective treatment range).
Exclusion Criteria
- •Subjects who meet any of the following criteria should be excluded from the study:
- •Subjects who received other investigational products or devices in other clinical trials within 4 weeks before the first dose;
- •Subjects who received anti-tumor therapy (except for mitomycin, nitrosourea, and fluorouracil oral drugs) within 4 weeks before the first dose, including but not limited to chemotherapy, radiotherapy (palliative radiotherapy is completed at least 2 weeks before the first dose can enroll), targeted therapy or immunotherapy.
- •Note: Mitomycin and nitrosourea have been treated within 6 weeks after the last dose; oral fluorouracil such as tegafur and capecitabine has been treated within 2 weeks after the last dose.
- •Subjects who previously received FGFR1-3 specific inhibitor therapy.
- •Subjects who have previous toxicity of anti-tumor therapy that has not been returned to level 0 or
- •(Alopecia, chemotherapy-induced peripheral neurotoxicity and ototoxicity ≤ Grade 2 can enroll);
- •Subjects who received a CYP3A4 and/or CYP2C8 strong inhibitor or a CYP3A4 strong inducer (see Appendix 6) within 7 days prior to the first dose, and need to continue using these drugs;
- •Subjects who have any of the following eye diseases/conditions:
- •History of retinal pigment epithelial detachment (RPED);
Arms & Interventions
Open-Label, Dose-Escalation
The starting dose in this dose-escalation study is 50 mg, and the preset 6 dose-escalation cohorts are 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, and 300 mg, respectively. This study adopts an i3+3 method for dose escalation. All subjects in each cohort will receive a single oral dose of 3D185, followed by a 7-day washout period (i.e. single-dose PK study period). Then, subjects will receive consecutive daily doses (Once daily \[QD\], 28 days/cycle) until disease progression, death, unacceptable toxicity, or withdraw of informed consent, whichever comes first
Intervention: Highly selective FGFR1-3 inhibitor
Outcomes
Primary Outcomes
Safety Evaluation: frequency and severity of AEs
Time Frame: 24 months
Evaluated based on the frequency and severity of AEs according to NCI CTCAE v4.03.
Tolerability Evaluation: frequency and severity of AEs
Time Frame: 24 Months
based on the frequency and severity of AEs according to NCI CTCAE v4.03.
Secondary Outcomes
- Efficacy evaluation: Complete Response(24 months)
- Pharmacokinetics (PK) evaluation: Cmax (mg/L)(24 months)
- PK evaluation: Tmax (minutes)(24 months)
- PK evaluation: AUC0-24 h, AUC0-96 h, AUC0-∞,(24 months)
- PK evaluation: t1/2(24 months)
- PK evaluation: Clearance(24 months)
- PK evaluation: Vd.(24 months)
- Progressive Disease evaluation(24 months)
- Efficacy evaluation: Partial Response(24 months)
- Efficacy evaluation: Stable Disease(24 months)
- Efficacy evaluation: Disease Progression(24 months)
- Objective Response Rale (ORR) (CR+PR)(24 months)
- disease control rate (DCR) (CR+PR+SD)(24 months)