A Phase 1 Study of YZJ-5053 Tablets in Participants With Advanced Solid Tumors

NCT06209385 | Recruiting Phase 1

• 1 other identifier: YZJ-5053-1-01
• Study Type: interventional
• Target: 157
• Locations: 1 country
• Sites: 4

Brief Summary

The goal of this study is to evaluate Safety, Tolerability, Pharmacokinetics and Efficacy of YZJ-5053 Tablets in Participants with Advanced Solid Tumors

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (3)

• Determination of Maximum Tolerated Dose (MTD) of YZJ-5053

  The MTD will be based on dose limiting toxicity (DLT)

  21days as a cycle

• To identify a recommended Phase 2 dose (RP2D) of YZJ-5053

  RP2D will be be based on MTD

  21days as a cycle

• Number of participants with treatment-related adverse events as assessed by National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0)

  All events with a Grade 3 or above toxicity (defined by the NCI-CTCAE 5.0) will be tabulated by event and by relationship to YZJ-5053

  21days as a cycle

Secondary Outcomes (10)

• Maximum observed plasma concentration (Cmax) of YZJ-5053

  single dose: predose, 0.5、1、2、4、6、8、12、24、48、72 hours post-dose. multiple dose: predose on days 1、3、4、5、6, and 0.5、1、2、4、6、8、12 hours post-dose on day 5

• Time to reach Cmax (Tmax) of YZJ-5053

  single dose: predose, 0.5、1、2、4、6、8、12、24、48、72 hours post-dose. multiple dose: predose on days 1、3、4、5、6, and 0.5、1、2、4、6、8、12 hours post-dose on day 5

• Terminal half-life (t1/2) of YZJ-5053

  single dose: predose, 0.5、1、2、4、6、8、12、24、48、72 hours post-dose. multiple dose: predose on days 1、3、4、5、6, and 0.5、1、2、4、6、8、12 hours post-dose on day 5

• Area under the plasma concentration-time curve (AUC) of YZJ-5053

  single dose: predose, 0.5、1、2、4、6、8、12、24、48、72 hours post-dose. multiple dose: predose on days 1、3、4、5、6, and 0.5、1、2、4、6、8、12 hours post-dose on day 5

• apparent clearance following oral administration for YZJ-5053

  single dose: predose, 0.5、1、2、4、6、8、12、24、48、72 hours post-dose. multiple dose: predose on days 1、3、4、5、6, and 0.5、1、2、4、6、8、12 hours post-dose on day 5

Study Arms (1)

YZJ-5053 tablets

EXPERIMENTAL

YZJ-5053 tablets will be administrated orally quaque die (QD) for 21 days

Drug: YZJ-5053 tablets

Interventions

YZJ-5053 tablets DRUG

YZJ-5053 tablets will be administrated orally QD for 21 days

Also known as: SHY-1901

YZJ-5053 tablets

Eligibility Criteria

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

You may qualify if:

• Male or female subjects are ≥ 18 years of age on the day of signing the informed consent.
• Histologically or cytologically confirmed advanced or metastatic solid tumors who have failed standard treatment, or are ineligible for the standard treatment, or have no standard treatment, or declined standard treatment.
• Subjects must have at least one measurable target lesion in indication expansion phase (Part 2) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria which has not received radiotherapy (or progressive disease after radiotherapy), or at least one evaluable lesion in dose escalation phase (Part 1) .
• Subjects with previously confirmed brain metastases were enrolled if they were clinically asymptomatic, in stable condition, and did not require steroid therapy for at least 4 weeks before the initiation of study treatment.
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1;
• Life expectancy at least 3 months;
• Adequate hematologic and organ function at screening and within 28 days prior to initiation of study treatment (without receiving any blood transfusion or hematopoietic stimulating factors within 2 weeks prior to screening),as evidenced by:
• absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L； Platelets ≥ 75 x 10\^9/L； Hemoglobin ≥85 g/L； aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN) , or ≤ 5 x ULN if liver cancer or liver metastases are present.
• Total bilirubin \< 1.5 x ULN , or \< 3.0 x ULN for subjects with liver cancer or liver metastases or documented Gilbert's syndrome (unconjugated hyperbilirubinemia)； Serum creatinine (Scr) \<1.5×ULN, or creatinine clearance (Ccr) \> 50 mL/min according to Cockcroft-Gault equation; international normalized ratio (INR) and activated partial thromboplastin time (APTT) \< 1.5 ULN;
• A woman of child-bearing potential (WOCBP) must have a negative serum pregnancy test prior to initiation of study treatment (serum pregnancy test is not required for females of nonchild-bearing potential who have undergone surgical sterilization, such as hysterectomy and/or bilateral oophorectomy, or those who have not experienced menses for 12 consecutive months and are judged to be postmenopausal based on factors such as age and castration therapy).
• Subjects must agree to use adequate contraceptive methods prior to initiation of study treatment, during the study, and for at least 28 days following the last dose of YZJ-5053 tablets.

You may not qualify if:

• Female subjects who are pregnant or breast-feeding.
• History of malignancy within 3 years prior to screening, with the exception of the cancer under investigation in this study and curatively treated carcinoma in situ of the cervix, non-melanoma skin cancer, localized prostate cancer or any other tumor that has been treated curatively and with no evidence of disease for at least 3 years (for indication expansion phase \[1b\] only).
• Presence of uncontrolled pleural effusion, pericardial effusion, or ascites that require recurrent drainage procedures (monthly or more frequently).
• Impaired cardiac function or clinically significant cardiovascular disease.
• Conditions or diseases that impair gastrointestinal (GI) function which may significantly alter the absorption of YZJ-5053 tables (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• Subjects with active infection requiring intravenous (IV) antibiotics at the time of screening or within 2 weeks prior to initiation of study treatment.
• Subjects with positive HIV antibody, or positive hepatitis B surface antigen (HBsAg) with hepatitis B virus (HBV) DNA ≥2×10\^3 IU/ml (equivalent to 10\^4 copies/ml), or positive hepatitis C virus antibody at the time of screening;
• Have received chemotherapy within 3 weeks, and radiotherapy, biological therapy, endocrine therapy, targeted therapy, immunotherapy or any other anti-tumor therapy within 4 weeks prior to initiation of study treatment.
• Subject who could not discontinue use of strong inhibitors or strong inducers of Cytochrome P450 3A (CYP3A) and Cytochrome P450 2C8 (CPY2C8) during the study period.
• Subjects who have received a live vaccine or live attenuated vaccine within 4 weeks prior to initiation of study treatment.
• Subjects who have previously received adenosine A2a receptor (A2aR) antagonists or A2aR/adenosine A2b receptor (A2bR) antagonists.
• Adverse events (AEs) from previous antitumor therapy have not recovered to baseline or to CTCAE Grade 1 prior to initiation of study treatment, excluding subjects with alopecia (any grade), peripheral sensory neuropathy (Grade ≤ 2), and any other toxicities of no clinical significance (Grade ≤ 2);
• Subjects with a known history of autoimmune thyroid disease such as diffuse toxic goiter (Graves disease) , acute or subacute thyroiditis. Subjects with active autoimmune diseases or a known history of autoimmune diseases that potentially relapsing, exception:
• Subjects with autoimmune-related hypothyroidism requiring stable dose thyroxine replacement only are eligible; Subjects with type I diabetes mellitus controlled on a stable insulin regimen are eligible;
• Subjects who have received systemic corticosteroids (\> 10 mg/day prednisone equivalent) or other systemic immunosuppressants (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor drugs) within 4 weeks prior to the initiation of study treatment, but excluded:

Sponsors & Collaborators

• Shanghai Haiyan Pharmaceutical Technology Co., Ltd.: lead

Study Sites (4)

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330000, China

NOT YET RECRUITING

Shandong Cancer Hospital

Jinan, Shandong, 250000, China

NOT YET RECRUITING

Shanghai East Hospital

Shanghai, Shanghai Municipality, 200120, China

RECRUITING

The Second Affiliated Hospital Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

NOT YET RECRUITING

Study Officials

• Jin Li

  Shanghai East Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yan Shi

CONTACT

021-38804518; shdfgcp@163.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

Model Details: Dose escalation and dose expansion

Study Record Dates

• First Submitted: December 17, 2023
• First Posted: January 17, 2024
• Study Start: August 11, 2023
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: January 17, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)