YL-13027 in Patients With Advanced Solid Tumors

NCT05228600 | Unknown Phase 1 FDA Drug

• 1 other identifier: YL-13027-003
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (1)

• Frequency, duration and severity of Adverse Events and Serious Adverse Events

  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.

  Throughout the study for approximately 2 years

Secondary Outcomes (6)

• Pharmacokinetics

  Throughout the study for approximately 2 years

• ORR

  Throughout the study for approximately 2 years

• DOR

  Throughout the study for approximately 2 years

• PFS

  Throughout the study for approximately 2 years

• Duration of Stable Disease

  Throughout the study for approximately 2 years

Other Outcomes (1)

• Plasma tumor antigens

  Throughout the study for approximately 2 years

Study Arms (1)

YL-13027

EXPERIMENTAL

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.

Drug: YL-13027

Interventions

YL-13027 DRUG

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.

YL-13027

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 1.1.
• 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)
• × 109/L Platelets
• × 109/L Hemoglobin
• 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)
• mL/min for patient with creatinine levels \>1.5 × institutional ULN Hepatic Total bilirubin
• × ULN or direct bilirubin ≤ULN for patients with total bilirubin levels \> 1.5× ULN Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
• × ULN or ≤5 × ULN for patients with liver metastases Cardiac CK-MB, Troponin T, BNP \< ULN
• Has a ECOG performance status of 0-1.
• Life expectancy \>12 weeks at baseline.
• 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.
• 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.

You may not qualify if:

• 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).
• Any clinically significant abnormalities (as assessed by the Investigator) in rhythm, conduction, or morphology of resting electrocardiograms (ECGs), e.g., complete left bundle branch block or third-degree heart block.
• Acute coronary syndrome within 6 months.
• Clinically significant cardiac arrhythmia.
• Mean QTC interval corrected (Frederica) for heart rate \>470 ms.
• Left ventricular ejection fraction (LVEF) \<50% or the lower limit of normal (per institutional standard).
• Evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, uncontrolled diabetes mellitus, active bleeding diatheses, or active infection, as determined by the investigator.

Sponsors & Collaborators

• Shanghai YingLi Pharmaceutical Co. Ltd.: lead
• Yingli Pharma US, Inc: collaborator

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Study Officials

• Jordi Ah Rodon, Ph D

  MD Anderson Cancer Center Houston TX 77030

  PRINCIPAL INVESTIGATOR

• Trisha Wi Draper, Ph D

  University of Cincinnati Cincinnati, OH 45267-0562

  PRINCIPAL INVESTIGATOR

• Martin E Gutierrez, MD

  Hackensack University Medical Center Hackensack, NJ 07601

  PRINCIPAL INVESTIGATOR

• Ignacio Ga Laguna,, MD, Ph.D

  Huntsman Cancer Institute Salt Lake City, UT 84112

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Meiyue Hong

CONTACT

13918087228; myhong@yl-pharma.com

Trisha W Draper, Ph D

CONTACT

Cincinnati, OH 45267-0562; myhong@yl-pharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2021
• First Posted: February 8, 2022
• Study Start: May 17, 2022
• Primary Completion: December 30, 2022
• Study Completion: December 1, 2023
• Last Updated: May 20, 2022

Record last verified: 2021-12

Locations

US (1)