A Multi-Center, Open-Label, Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumor Activity of YL-13027 in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- YL-13027
- Conditions
- Solid Tumor
- Sponsor
- Shanghai YingLi Pharmaceutical Co. Ltd.
- Enrollment
- 54
- Locations
- 1
- Primary Endpoint
- Frequency, duration and severity of Adverse Events and Serious Adverse Events
- Last Updated
- 3 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •In order to be eligible for participation in this trial, the patient must meet all the following inclusion criteria:
- •Patients with advanced solid tumors that is unresectable or metastatic and considered refractory to or not candidates for all available approved therapy.
- •Measurable disease with at least one lesion amenable to response assessment per RECIST 1.
- •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
Exclusion Criteria
- •The patient will be excluded from participating in the trial if any of the following exclusion criteria are met:
- •Prior therapy with a TGF-ß signaling targeted agent.
- •Known symptomatic brain metastases requiring steroids above physiologic replacement doses.
- •Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment.
- •Live vaccines within 30 days of study treatment.
- •Unresolved toxicities from prior therapy, defined as having not resolved to NCI CTCAE v.5.0 Grade ≤1 or baseline, with exception of endocrinopathies from prior therapy and successfully treated (such as hypothyroidism), alopecia, vitiligo, and ≤ grade 2 peripheral neuropathy.
- •Human immunodeficiency virus (HIV) infection with a current or a known history of AIDS-defining illness or HIV infection with a CD4+ T cell count \<350 cells/μL and an HIV viral load more than 400 copies/μL.
- •Patients with active viral (any etiology) hepatitis are excluded. However, patients with serologic evidence of chronic hepatitis B virus (HBV) infection (defined by a positive hepatitis B surface antigen test and a positive anti-hepatitis core antigen antibody test) who have a viral load below the limit quantification (HBV DNA titer \<1000 cps/mL or 200 IU/mL), and are not currently on viral suppressive therapy may be eligible and should be discussed with the Medical Monitor. Patients with a history of hepatitis C virus (HCV) infection who have completed curative antiviral treatment and have a viral load below the limit of quantitation may be eligible and should be discussed with the Medical Monitor.
- •Any of the following cardiac criteria experienced currently or within the last 6 months:
- •Congestive heart failure (New York Heart Association ≥ Class 2).
Arms & Interventions
YL-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.
Intervention: YL-13027
Outcomes
Primary Outcomes
Frequency, duration and severity of Adverse Events and Serious Adverse Events
Time Frame: 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 Outcomes
- PFS(Throughout the study for approximately 2 years)
- Clinical Benefit Rate(Throughout the study for approximately 2 years)
- Pharmacokinetics(Throughout the study for approximately 2 years)
- ORR(Throughout the study for approximately 2 years)
- DOR(Throughout the study for approximately 2 years)
- Duration of Stable Disease(Throughout the study for approximately 2 years)