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

TYK Medicines

Status and phase: Unknown; Phase 1

Conditions: Solid Tumor; Breast Cancer

Treatments: Drug: TY-302: capsule, 25mg/50mg ; Tamoxifen: tablet,10mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT04433494

TYKM1602101

Details and patient eligibility

About

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

Full 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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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60 participants in 1 patient group

TY-302 ; TY-302 combine with Tamoxifen

Experimental group

Description:

1. TY-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. 2. 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. 3. 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.

Treatment:

Drug: TY-302: capsule, 25mg/50mg ; Tamoxifen: tablet,10mg