Dose Escalation and Expansion Study of SYH2043 in Patients With Advanced Malignant Tumors

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Profile and Preliminary Efficacy of SYH2043 in Patients With Advanced Malignant Tumors

The aim of this study is designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of SYH2043 in patients with advanced malignant tumors.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Malignant Tumors
• Intervention / Treatment: Drug: SYH2043

Detailed Description

This study is an open-label, single-arm, multi-center Phase I clinical study, which includes four stages:

A: Dose-escalation Stage: The dose escalation stage is divided into 5 dose levels, and a Bayesian Optimal Interval Design (BOIN) including accelerated titration will be used for dose escalation.

B: PK Expansion Stage: Two or three dose groups will be selected for PK expansion; After PK extension the cohort extension study will be conducted as required, and will include 4 cohorts according to the tumor types.

C: Combination dose Escalation: This study will use a 3+3 design with up to 2 dose escalation cohorts at increasing levels.

D: According to the results of stage C, 1-2 combination doses will be selected for combination dose expansion, and Simon 2 stage was adopted for the expansion stage.

• Study Type: Interventional
• Enrollment (Anticipated): 367
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Cancer Hospital Chinese Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. Patients aged 18-75 years (inclusive);
• 2. Histological or cytological confirmation of advanced malignant tumors;

• 3. Patients who failed or were intolerant to standard treatment or had no standard treatment, and meet the criteria as below of the corresponding stages:

  • Part A and PK Expansion Stage of part B: advanced malignant tumors;
  • Cohort extension of part B: solid tumors such as locally advanced/metastatic breast cancer, relapsed/refractory ovarian cancer, locally advanced/metastatic liver cancer, etc;
  • Part C and D: locally advanced/metastatic breast cancer with histological confirmation of ER+, HER2-;
• 4. With at least one measurable lesion according to RECIST v1.1;
• 5. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1;
• 6. Life expectancy greater than 3 months;

• 7. Main organs meet the following criteria within 7 days before treatment:

  • Hematology: no component blood transfusion, human granulocyte colony-stimulating factor (G-CSF), and erythropoietin (EPO) within 2 weeks prior to the investigational drug administration
  • Absolute neutrophil count (ANC) ≥1.5×10^9/L;
  • Platelet count (PLT) ≥90×10^9/L;
  • Hemoglobin (HGB) ≥90 g/L or ≥5.6 mmol/L;
  • Renal Function: Serum creatinine ≤ 1.5×ULN or creatinine clearance rate ≥ 50 mL/min;
  • Liver function: Total bilirubin (TBIL) ≤ 1.5×ULN, or ≤ 3×ULN for patients with Gilbert syndrome; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)≤ 2.5×ULN, or ≤ 5×ULN in case of liver metastases;
  • Coagulation Function: Activated partial thromboplastin time (APTT)≤ 2×ULN; International normalized ratio (INR)≤ 2×ULN;
• 8. The serum pregnancy test for women of childbearing potential (WOCBP) is negative within 7 days prior to the first dose of the investigational drug. Patient and his/her spouse must agree to take adequate contraception from signing of ICF to 6 months after the last dose, during which women should be non-lactating and men should refrain from donating sperms;
• 9. Patients voluntarily participate in this clinical study, understand the study procedures and sign the ICF.

Exclusion Criteria:

• 1. Have received anti-tumor treatments such as chemotherapy, radiotherapy, endocrine therapy, targeted therapy, immunotherapy, etc. within 4 weeks before the first dose of the investigational drug;
• 2. Have received other unmarketed clinical investigational drugs or treatments within 4 weeks before the first dose of the investigational drug;
• 3. Have received major surgery (excluding needle biopsy), or severe unhealed wounds, trauma, etc. within 4 weeks before the first dose of the investigational drug in the study;
• 4. Have received glucocorticoids for systemic therapy over 7 days (Prednisone>10 mg/day or equivalent doses) or other immunosuppressant within 2 weeks before the first dose of investigational drug, and patients who need long-term use these therapies;
• 5. Have received potent inhibitors or inducers of CYP3A4 and inhibitors of P-gp within 1 weeks before the first dose of the investigational drug;
• 6. The adverse events due to previous anti-tumor treatments without recovering to Grade 1 (except for alopecia; some toxicities may be excluded as judged by the investigator) according to NCI-CTCAE v5.0;
• 7. Breast cancer patients with visceral crisis or symptomatic visceral metastasis;
• 8. With active central nervous system (CNS) metastasis and/or cancerous meningitis;
• 9. Active HBV or HCV infection (HbsAg positive and/or HBcAb positive with HBV DNA ≥ 2000 IU/mL, and HCVAb positive with HCV RNA positive), or HIV positive;
• 10. Participants with a history of severe cardiovascular disease;
• 11. Inability to swallow medications orally, or conditions that, in the judgment of the investigator, significantly affect gastrointestinal absorption;
• 12. Patients who have received a live attenuated vaccine within 2 weeks before the first use of the investigational drug or plan to receive during the study;
• 13. Other situations that the investigator considers not suitable for participating in the clinical study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SYH2043; Patients will receive SYH2043 once everyday on day 1-21 of each 28-day cycle	Drug: SYH2043; Patients will receive SYH2043 once everyday on day 1-21 of each 28-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AE	Occurrence and frequency of Adverse Event	Up to approximately 3 years
SAE	Serious Adverse Event	Up to approximately 3 years
DLT	Dose-limiting Toxicity (DLT)	At the end of Cycle 1 (each cycle is 28 days)
MTD	The maximum tolerated dose (MTD) (if available)	At the end of Cycle 1 (each cycle is 28 days)
RP2D	Recommended phase 2 dose (RP2D) in stage A	At the end of Stage A (approximately 1 year)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC	Area under the plasma concentration versus time curve (AUC)	Up to approximately 3 years
Cmax	Peak Plasma Concentration (Cmax)	Up to approximately 3 years
t1/2	Half-life (t1/2)	Up to approximately 3 years
Tmax	Time to peak drug concentration (Tmax)	Up to approximately 3 years
Vz/F	Apparent volume of distribution	Up to approximately 3 years
CL/F	Apparent clearance	Up to approximately 3 years
pRb	Explore the relationship between phosphor-retinoblastoma protein (pRb) and efficacy	Up to approximately 3 years
ORR	Objective Response Rate	Up to approximately 3 years
PFS	Progression-free Survival	Up to approximately 3 years
OS	Overall Survival	Up to approximately 3 years
DoR	Duration of Response (DoR)	Up to approximately 3 years
DCR	Disease Control Rate (DCR)	Up to approximately 3 years

Collaborators and Investigators

• Sponsor: CSPC Ouyi Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2023
• Primary Completion (Anticipated): February 1, 2026
• Study Completion (Anticipated): March 1, 2026

Study Registration Dates

• First Submitted: January 27, 2023
• First Submitted That Met QC Criteria: February 5, 2023
• First Posted (Actual): February 15, 2023

Study Record Updates

• Last Update Posted (Actual): February 17, 2023
• Last Update Submitted That Met QC Criteria: February 15, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: SYH2043-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No