A Study to Investigate the Safety of SYHA1815 in Subjects With Unresectable Locally Advanced or Metastatic Solid Tumors

NCT05105464 | Unknown Phase 1

• 1 other identifier: SYHA1815-202001/PRO
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multi-center, open-label, dose escalation and expansion, phase I study to investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) characteristics, preliminary efficacy of SYHA1815 in subjects with unresectable locally advanced or metastatic solid tumors. Once the expected effective dose is identified, the dose expansion study will be started to further evaluate the safety, clinical activity and PK profile of SYHA1815 in subjects with unresectable locally advanced or metastatic solid tumors.

Conditions

Locally Advanced Unresectable Carcinoma

Keywords

Locally advanced unresectable or metastatic solid tumors

Outcome Measures

Primary Outcomes (9)

• Number of participants with Dose-limiting Toxicities

  Number of participants with Dose-limiting Toxicities

  Baseline through 28 days after the first dose of study drug

• Incidence of adverse events and SAEs

  Incidence of adverse events and SAEs defined by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE V5.0).

  Up to 3 years

• Clinically significant changes from baseline in routine blood test

  Clinically significant changes from baseline in routine blood test

  Up to 3 years

• Clinically significant changes from baseline in blood biochemistry test

  Clinically significant changes from baseline in blood biochemistry test

  Up to 3 years

• Clinically significant changes from baseline in routine urine test

  Clinically significant changes from baseline in routine urine test

  Up to 3 years

• Clinically significant changes from baseline in coagulation function test

  Clinically significant changes from baseline in coagulation function test

  Up to 3 years

• Clinically significant changes from baseline in 12-lead electrocardiogram (ECG)

  Clinically significant changes from baseline in 12-lead electrocardiogram (ECG)

  Up to 3 years

• Clinically significant changes from baseline in vital signs examination

  Clinically significant changes from baseline in vital signs examination

  Up to 3 years

• Clinically significant changes from baseline in physical examination

  Clinically significant changes from baseline in physical examination

  Up to 3 years

Secondary Outcomes (19)

• Objective Response Rate (ORR)

  Up to 3 years

• Disease control rate (DCR)

  Up to 3 years

• Duration of response (DOR)

  Up to 3 years

• Progression free survival (PFS)

  Up to 3 years

• Time to maximum plasma concentration (Tmax)

  Up to 3 years

Study Arms (2)

Dose Escalation Cohort

EXPERIMENTAL

Six dose levels will be tested. The dose-limiting toxicity (DLT) will be assessed from the first administration of SYHA1815 to the end of the first cycle (28 days).

Drug: SYHA1815

cohort Expansion Cohort

EXPERIMENTAL

Once the expected effective dose is determined, four expansion cohorts will be started to further evaluate the safety, clinical activity and PK profile of SYHA1815.

Drug: SYHA1815

Interventions

SYHA1815 DRUG

Subjects will receive SYHA1815 orally.

Also known as: SYHA1815 tablet

Dose Escalation Cohort; cohort Expansion Cohort

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects aged 18 to 75 years (inclusive)；
• Histologically or cytologically confirmed diagnosis of unresectable locally advanced or metastatic solid tumors (thyroid cancer, non-small cell lung cancer, gastric cancer \[including gastroesophageal junction cancer\], colorectal cancer, pancreatic cancer, soft tissue sarcoma, etc.), failure of standard treatment (disease progression or intolerance), or no alternative standard treatment or refusal of standard treatment;
• The subjects included in the dose expansion study should provide written biomarker test reports or tumor tissue samples to the central laboratory;
• The time interval between the last dose of anti-tumor drug and the first administration of SHYA1815 must meet the following conditions: ≥ 4 weeks for cytotoxic drugs, PD-1 / PD-L1, cellular immunotherapy; ≥2 weeks for oral molecular targeted drug therapy; ≥4 weeks for radiotherapy (≥ 2 weeks for palliative local radiotherapy for pain relief), and had recovered from the toxicities of radiotherapy; ≥2 weeks for anticancer Traditional Chinese medicine or Chinese patent medicine;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
• Life expectancy ≥ 12 weeks;
• At least one measurable lesion according to RECIST 1.1 at the screening phase;
• The organ function level and related laboratory values of the subjects must meet the following requirements within 7 days before the first dose of study drug (not receiving blood transfusion within 14 days before the first administration):
• Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L; Platelet count ≥ 75 × 10\^9/L /L; Hemoglobin ≥ 90 g / L; the values of blood phosphorus and calcium are in normal range;
• Blood biochemistry: serum total bilirubin ≤ 1.5× upper limit of normal value (ULN); AST / ALT ≤ 3 ×ULN (≤ 5 ×ULN for liver metastasis); Serum creatinine ≤ 1.5 × ULN;
• Coagulation: Internationally standardized ratio (INR) or prothrombin time (PT) ≤ 1.5×ULN, activated partial thrombin time (APTT) ≤ 1.5×ULN;
• For women of childbearing potential: the serum pregnancy test within 7 days before the first administration must be negative, and female subjects are willing to take adequate contraceptive measures during the treatment period and for at least 3 months after the last dose of the study drug. Male subjects must agree to take contraceptive measures (non-drug or instrumental contraception) from the beginning of the study to at least 3 months after the last dose of study drug;
• Voluntarily participate in the study and sign the informed consent form.

You may not qualify if:

• The previous anti-tumor or surgical treatment history with any of the following conditions:
• Received the treatment of other intervention clinical studies with 4 weeks before the first dose of study drug;
• Had undergone major surgery within 4 weeks before the first dose of study drug or had not fully recovered from any previous invasive operation;
• Prior treatment of RET/FGFR inhibitors or small molecular kinase inhibitors with RET/FGFR as the main targets;
• Any unresolved toxicities from prior anti-tumor therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1, except for alopecia, pigmentation, previous chemotherapy-related neurotoxicity (≤ grade 2) and other adverse reactions judged no safety risk by the investigators;
• Subjects with symptomatic brain metastasis or meningeal metastasis, spinal cord compression or mental disorder, and asymptomatic brain metastasis can be enrolled (there is no disease progress within at least 4 weeks after radiotherapy and/or no neurological symptoms after surgical resection, and glucocorticoids, anticonvulsant drugs and mannitol are not required);
• Impaired cardiac function or clinically significant cardiovascular and cerebrovascular diseases, including any of the following:
• History of myocardial infarction, congestive heart failure (NYHA grade ≥ grade III), and unstable angina pectoris within 6 months prior to screening;
• Cerebrovascular disease occurred within 6 months before screening (except for transient ischemic attack (TIA), lacunar infarction with no clinical significance);
• Severe uncontrollable arrhythmia requiring medical treatment;
• Electrocardiogram (ECG) examination, female QTc interval\>470 milliseconds (ms), male QTc interval\>450 milliseconds (ms) according to Fridericia formula;
• The left ventricular ejection fraction is less than 50% according to cardiac ultrasound examination;
• History of active bleeding within 6 months before screening;
• Any serious or uncontrollable disease, and not suitable for this study as determined by the investigator;
• Any uncontrollable active infection that will prevent the subjects from receiving the study drug within 2 weeks prior to the first dose of study drug;

Sponsors & Collaborators

• Shanghai Runshi Pharmaceutical Technology Co., Ltd: lead
• Jilin Provincial Tumor Hospital: collaborator

Study Sites (1)

Jilin Cancer Hospital

Changchun, Jilin, 130012, China

RECRUITING

Study Officials

• Huang Yanli, PD

  CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd

  STUDY DIRECTOR

Central Study Contacts

Yang Li, AM

CONTACT

13321898532; lcliyang@mail.ecspc.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2021
• First Posted: November 3, 2021
• Study Start: June 25, 2021
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2023
• Last Updated: November 3, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)