Clinical Trials /

A Study of TY-302 in Patients With Advanced Solid Tumors

NCT04433494

Description:

The primary objective of this study is to evaluate the safety and tolerability of TY-302 single and the combination with Tamoxifen in dose-escalation and dose-expansion study.The drugs involved in this study are: - TY-302 - Tamoxifen

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of TY-302 in Patients With Advanced Solid Tumors
  • Official Title: A Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetic Characteristics of TY-302 Capsules in Patients With Advanced Solid Tumors in China

Clinical Trial IDs

  • ORG STUDY ID: TYKM1602101
  • NCT ID: NCT04433494

Conditions

  • Breast Cancer
  • Solid Tumor

Interventions

DrugSynonymsArms
TY-302: capsule, 25mg/50mg ; Tamoxifen: tablet,10mgTY-302, Tamoxifen CitrateTY-302 ; TY-302 combine with Tamoxifen

Purpose

The primary objective of this study is to evaluate the safety and tolerability of TY-302 single and the combination with Tamoxifen in dose-escalation and dose-expansion study.The drugs involved in this study are: - TY-302 - Tamoxifen

Detailed Description

      This is an open-label, single-arm, phase I trial. The purpose of this study is to :

        -  Test a safe and tolerable dose of TY-302 single and the combination with Tamoxifen

        -  Determine the response rate of the combination

        -  Further evaluate the safety and side effect profile for the combination of TY-302 and
           Tamoxifen.
    

Trial Arms

NameTypeDescriptionInterventions
TY-302 ; TY-302 combine with TamoxifenExperimentalTY-302 Find the maximum tolerated dose(MTD) and the recommended phase 2 dose (RP2D) of TY-302, given orally. Increased dose cohorts from low dose to MTD, starting at 25mg daily. TY-302 combine withTamoxifen in dose-escalation stage TY-302: RP2D-1to RP2D daily for 28 days of each 28 day cycle. Tamoxifen: 20mg twice daily for 28 days of each 28 day cycle. TY-302 combine withTamoxifen in dose-expansion stage TY-302: RP2D daily for 28 days of each 28 day cycle. Tamoxifen: 20mg twice daily for 28 days of each 28 day cycle.
  • TY-302: capsule, 25mg/50mg ; Tamoxifen: tablet,10mg

Eligibility Criteria

        Inclusion Criteria:

          1. 18-70years old, male or female with solid tumors, female with breast cancer

          2. Histological or cytological confirmation diagnosis of advanced solid tumors (except
             small cell lung cancer and eye cancer) in TY-302 alone study; and advanced breast
             cancer in the combination study.

          3. Biopsy proven diagnosis of ER and/or PR positive, HER2 negative.

          4. At least one measurable lesion according to Response Evaluation Criteria in Solid
             Tumours (RECIST) version 1.1.

          5. Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.

          6. Life expectancy of at least 3 month.

          7. Adequate organ function as defined by the following criteria:

             Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤2.5 x upper
             limit of normal (ULN), or AST and ALT ≤5 x ULN if liver function abnormalities are due
             to underlying malignancy; total serum bilirubin ≤1.5 x ULN; Absolute neutrophil count
             (ANC) ≥1.5×109/L; platelets(PLT)≥75×109/L ; Hemoglobin(Hb) ≥ 90g/L; Serum creatinine
             ≤1.5 x ULN; Left ejection fraction (LVEF)≥50%; QTc≤470 msec (based on the mean value
             of the triplicate ECGs).

          8. Female subjects have a negative urine or serum pregnancy.

          9. Provision of signed and dated, written informed consent prior to any study specific
             procedures, sampling and analyses.

        Exclusion Criteria:

        Subjects presenting with any of the following were not to be included in the study:

          1. Previously treated by other CDK4/6 inhibitor.

          2. Hypersensitivity to TY-302(or Tamoxifen in the combination study) or to any of its
             excipients.

          3. Ocular fundus diseases in the combination study.

          4. Uncontrolled intercurrent illness including active infection, human immunodeficiency
             virus infection, active hepatitis or other severe acute or chronic medical or
             psychiatric condition.

          5. Current alcohol/drug abuse or dependence.

          6. Any of the following in the previous 6 months: myocardial infarction, severe/unstable
             angina, ongoing cardiac dysrhythmias of NCI CTCAE grade≥2, atrial fibrillation of any
             grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure
             of NCI CTCAE grade≥2, cerebrovascular accident.

          7. Presence of a condition that would interfere with enteric absorption of TY-302 and/or
             Tamoxifen.

          8. Any cytotoxic chemotherapy, investigational agents or anticancer drugs for the
             treatment from a previous treatment regimen within 4 weeks of the first dose.

          9. Spinal cord compression or brain metastases unless asymptomatic.

         10. Major surgery within 8 weeks of first study treatment.

         11. Current use or anticipated need for drugs that are known strong CYP3A4 inhibitors,
             strong CYP3A4 inducers, Narrow therapeutic index for CYP3A sensitive substrates,
             CYP2D6 inhibitors, CYP2D6 inducers.

         12. Patients on chronic anticoagulation.

         13. The subject inappropriate for entry into this study in the judgment of the
             investigator.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of TY-302
Time Frame:1 year
Safety Issue:
Description:To determine the MTD and RP2D of TY-302 in subjects with solid tumors

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:TYK Medicines, Inc

Last Updated

June 15, 2020