Solid Tumor
Conditions
Brief summary
Part 1 (Phase Ia): This is a dose escalation, 3 + 3 design study, to evaluate the safety and tolerability, and to determine the RP2D of YL-13027 when administered b.i.d. in patients with advanced solid tumors. Up to 4 cohorts of 3-6 patients each will be treated in part 1 of the study. One cycle is 28 days. Part 2: This is a dose expansion phase to further evaluate the safety, tolerability and preliminary anti-tumor activity of YL-13027 at the RP2D.
Detailed description
3.1.3. Parts 1 and 2: Patients will receive study treatment until criteria for study termination are met. A Safety Follow-up Visit will be conducted 30 days (±7 days) after the last dose of study treatment Patients who discontinue study treatment for reasons other than disease progression will have post-treatment follow-up for disease assessment until start of new anticancer treatment, patient withdraws consent, is lost to follow-up, death, or until the Sponsor stops the study, whichever comes first. Adverse events will be assessed using the NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. Tumor response will be assessed by physical examination, computed tomography (CT) and/or magnetic resonance imaging (MRI) scan using RECIST 1.1 criteria, assessed by the investigator. Patients who discontinue study treatment for reasons other than disease progression will have post-treatment follow-up for disease assessment until start of new anticancer treatment, patient withdraws consent, is lost to follow-up, death, or until the Sponsor stops the study, whichever comes first. Specific procedures to be performed during the study, as well as their prescribed times and associated visit windows, are outlined in the Schedule of Activities (SoA) see Appendix 1. Details of each procedure are provided in Section 7. The Safety Monitoring Committee (SMC) will monitor safety during the duration of the study. The SMC will make reviews based on Investigator site dose adjustments, adverse events, serious adverse events or discontinuation study treatment and make any appropriate recommendations to the Sponsor.
Interventions
DRUGYL-13027
YL-13027 is a novel small molecule TGF-βR1 inhibitor. 1.1.1. Chemical Properties Chemical Name: 6-(5-fluoro-2-(6-methylpyridin-2-yl)phenyl)imidazo\[1,2-a\]pyridine-3-carboxamide Molecular Formula C20H15FN4O Molecular Weight 346.36 Formulation YL-13027 is provided as pink film coated tablets for oral administration in two strengths, 30 mg and 120 mg. Packaging and Storage YL-13027 tablets are packaged (30 tablets/bottle) in the 45 mL opaque HDPE bottles with child resistant polypropylene caps, induction-sealed inner polypropylene liners. YL-13027 tablets should be protected from light in a closed container and stored at room temperature. Stability The shelf-life of YL-13027 oral tablets is tentatively set at 24 months when stored at room temperature.
Sponsors
Yingli Pharma US, Inc
Shanghai YingLi Pharmaceutical Co. Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\- In order to be eligible for participation in this trial, the patient must meet all the following inclusion criteria: 1. Patients with advanced solid tumors that is unresectable or metastatic and considered refractory to or not candidates for all available approved therapy. 2. Measurable disease with at least one lesion amenable to response assessment per RECIST 1.1. 3. Demonstrate adequate organ function as defined below. All screening laboratories should be performed within 7 days of study treatment initiation. System Laboratory Value Hematological Absolute neutrophil count (ANC) * 1.5 × 109/L Platelets * 100 × 109/L Hemoglobin * 9 g/dL or ≥5.6 mmol/L Renal Creatinine\* or ≤1.5 × the upper limit of normal (ULN) or Measured or calculated creatinine clearance (CrCl) (Cockroft-Gault) * 50 mL/min for patient with creatinine levels \>1.5 × institutional ULN Hepatic Total bilirubin * 1.5 × ULN or direct bilirubin ≤ULN for patients with total bilirubin levels \> 1.5× ULN Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) * 2.5 × ULN or ≤5 × ULN for patients with liver metastases Cardiac CK-MB, Troponin T, BNP \< ULN 4. Has a ECOG performance status of 0-1. 5. Life expectancy \>12 weeks at baseline. 6. Women of childbearing potential must have negative serum or urine pregnancy test within 72 hours prior to receiving the first study drug administration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 7. For women of childbearing potential, must be willing to use an adequate method of contraception from 30 days prior to the first study drug administration and at least 3 months following last day study drug administration. 8. Male patients of childbearing potential must be surgically sterile, or must agree to use adequate method of contraception during the study and at least 3 months following the last day of study drug administration. 9. Age ≥18 years at screening. 10. Able and willing to provide written informed consent and to follow study instructions. 11. Washout from prior anti-tumor therapy: Previous Treatment Length of Time Prior to (Study entry/enrollment/first dose of study treatment) Cytotoxic therapies * 4 weeks Mitomycin C or nitrosoureas * 6 weeks Small molecule inhibitors * 2 weeks or 5x T1/2, whichever is longer Biologic agents (e.g., antibodies) * 4weeks Immunotherapy (e.g., CTLA4, PD-1, PD-L1 inhibitors) * 4 weeks Radiotherapy * 4 weeks Limited field radiotherapy or palliative radiotherapy * 2 weeks Major surgery, excluding biopsy * 4 weeks. Patients with recent major surgery must have recovered, in the opinion of the investigator, from the toxicity and/or complication from the intervention before starting therapy
Exclusion criteria
* The patient will be excluded from participating in the trial if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency, duration and severity of Adverse Events and Serious Adverse Events | Throughout the study for approximately 2 years | Primary Outcome Measure(s): Part 1: Frequency, duration and severity of Adverse Events and Serious Adverse Events. Part 2: Frequency, duration and severity of Adverse Events and Serious Adverse Events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics | Throughout the study for approximately 2 years | Secondary Outcome Measures: • Pharmacokinetics of YL-13027; to include: AUC, AUClast, AUCinf, AUMC, Cmin, Cmax, CL, T1/2, Tmax, and Vd |
| ORR | Throughout the study for approximately 2 years | Efficacy \- Overall Response Rate (ORR). |
| DOR | Throughout the study for approximately 2 years | • Efficacy \- Duration of Response (DOR). |
| Duration of Stable Disease | Throughout the study for approximately 2 years | Efficacy \- Duration of Stable Disease |
| Clinical Benefit Rate | Throughout the study for approximately 2 years | Efficacy \- Clinical Benefit Rate (CR+PR+SD) |
| PFS | Throughout the study for approximately 2 years | Efficacy \- Progression Free Survival (PFS). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Plasma tumor antigens | Throughout the study for approximately 2 years | Exploratory Outcome Measures: • Plasma tumor antigens (as appropriate to cancer type, e.g., CA19-9, CEA) and biomarkers of TGF-ß signaling. |
Countries
United States
Contacts
Primary ContactMeiyue Hong
Backup ContactTrisha W Draper, Ph D
Outcome results
None listed