CTS2190 Phase I /II Clinical Study in Patients

NCT06224387 | Recruiting Phase 1

• 1 other identifier: CTS2190-CI01
• Study Type: interventional
• Target: 224
• Locations: 1 country
• Sites: 2

Brief Summary

This is a first in human study in patients with advanced or metastatic solid tumors. The first part of the study is an open-label, dose escalation and the second part is an open label dose expansion in specific tumor types. The study drug, CTS2190, is a PRMT1 inhibitor administered orally. The study is planned to treat up to 224 participants.

Conditions

Solid Tumors; Pancreatic Cancer; Non-small Cell Lung Cancer; Triple-negative Breast Cancer

Keywords

Phase I/II; pharmacodynamic; Pharmacokinetics; Tolerability

Outcome Measures

Primary Outcomes (3)

• Dose Escalation：The maximum tolerated dose (MTD)

  The MTD is defined as the dose level at which the DLT rate is closest to the target toxicity incidence (i.e., 0.3) during the DLT observation period (within 25 days after the first administration).

  During the DLT observation period: 25 days after the first administration

• Dose Escalation：The recommended phase 2 dose (RP2D)

  The recommended phase 2 dose (RP2D) of CTS2190 Based on the review of all available data including, but not limited to, safety, tolerability, PK, PD and preliminary anti-tumor activity, RP2D may be determined.

  During the DLT observation period: 25 days after the first administration

• Dose Expansion：Objective response rate(ORR)

  The percentage of participants having complete response (CR) or partial response (PR))assessed based on RECIST V1.1.

  Every 6 weeks for the duration of study participation.

Secondary Outcomes (25)

• Pharmacokinetic (PK) characteristics:Peak concentration(Cmax)

  Day1 to Day 4 Multiple-dose stage: Cycle 1 (each cycle is 21 days) Day 8, Cycle 1 Day 15, Cycle 1 Day 16, Cycle 3 Day 1 and Cycle 5 Day 1

• Pharmacokinetic (PK) characteristics: time to peak concentration (Tmax)

  Single-dose stage: Day1 to Day 4; Multiple-dose stage: Cycle 1 (each cycle is 21 days) Day 8, Cycle 1 Day 15, Cycle 1 Day 16, Cycle 3 Day 1 and Cycle 5 Day1.

• Pharmacokinetic (PK) characteristics：area under concentration-time curve from zero to infinity (AUC0-∞)

  Single-dose stage: Day 1 to Day 4, Multiple-dose stage: Cycle 1 (each cycle is 21 days) Day 8, Cycle 1 Day 15, Cycle 1 D 16, Cycle 3 Day 1 and Cycle 5 Day 1

• Pharmacokinetic (PK) characteristics：area under concentration-time curve from zero to time of the last detectable concentration (AUC0-t)

  single-dose stage: Day 1 to Day 4

• Pharmacokinetic (PK) characteristics：elimination half-life (T1/2)

  single-dose stage: Day 1 to Day 4

Study Arms (1)

Dose Escalation/Dose Expansion

EXPERIMENTAL

4-6 dose groups are pre-specified in Dose Escalation,and 4 arms in Dose Expansion.

Drug: CTS2190 capsules

Interventions

CTS2190 capsules DRUG

4-6 dose groups are pre-specified in Dose Escalation,and 4 arms in Dose Expansion.

Also known as: CTS2190

Dose Escalation/Dose Expansion

Eligibility Criteria

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

You may qualify if:

• Subjects who meet all of the following criteria can be included in this study:
• Male or female ≥ 18 years of age at signing of ICF.
• Part 1: histologically or cytologically confirmed locally advanced or metastatic solid tumors at screening who cannot be treated surgically and have failed standard treatment (PD during treatment or after the last treatment) recommended by the current clinical diagnosis and treatment standards or guidelines, or cannot tolerate standard treatment, or refuse standard treatment and/or currently have no effective treatment available.
• Part 2: histologically or cytologically confirmed advanced solid tumors (including pancreatic cancer, non-small cell lung cancer and/or other tumors, such as gastric cancer, colorectal cancer, etc.) at screening who cannot be treated surgically and have failed standard treatment (PD during treatment or after the last treatment) recommended by the current clinical diagnosis and treatment standards or guidelines, or cannot tolerate standard treatment, or refuse standard treatment and/or currently have no effective standard treatment available.
• At least one measurable tumor lesion at screening \[according to RECIST V1.1 criteria (see appendix 1)\].
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 (Appendix 2) at screening.
• With a life expectancy ≥ 12 weeks at screening.
• With good organ function at screening, including:
• Liver function: total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN) (if the following conditions occur, isolated bilirubin \>1.5 × ULN is acceptable if: bilirubin is fractionated and direct bilirubin \<35%, or the patients is diagnosed with Gilbert syndrome), alanine aminotransferase (ALT) ≤ 2.5 × ULN, and aspartate aminotransferase (AST) ≤ 2.5 × ULN (for patients with liver metastases or tumor infiltration, the criteria can be relaxed to TBIL ≤ 1.5 × ULN, ALT ≤5 × ULN, and AST ≤ 5 × ULN);
• Renal function: blood creatinine ≤ 1.5 × ULN and creatinine clearance ≥ 50 mL/min \[calculate the creatinine clearance using Cockcroft-Gault formula (appendix 3)\];
• Hematology: platelet ≥ the lower limit of the laboratory normal range, and absolute neutrophil count (ANC) ≥ 1.5 × 109/L, and hemoglobin ≥ 100 g/dL;
• Cardiac function: QT interval corrected by Fridericia method (QTcF) ≤ 450 ms (male) or ≤ 470 ms (female) (see the appendix 3 for calculation formula).
• Coagulation function: International normalized ratio (INR) ≤ 1.5 × ULN, or activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
• Female patients of non-childbearing age or female patients of childbearing age who have negative pregnancy test results and promise to take sufficient and effective contraceptive measures or adhere to abstinence from the screening period to 90 days after the last administration, or male patients who promise to take sufficient and effective contraceptive measures or adhere to abstinence from the screening period to 90 days after the last administration (see the appendix 4). Patients are not allowed to donate sperm within 6 months from the start of administration to 6 months after the end of investigational drug administration.
• Patients who understand and voluntarily signs the ICF, are willing to and able to complete the scheduled visits, treatment plan, laboratory tests and other study procedures.

You may not qualify if:

• Subjects should not participate in this clinical study if any of the following conditions is met:
• Female patients in pregnancy or lactation.
• Patients with dysphagia.
• Patients who cannot tolerate venipuncture or have a history of syncope judged by the investigator to be clinically significant.
• Uncontrolled tumor-related pain.
• Allergic or intolerant to the active ingredients or excipients of the investigational drug judged by the investigator.
• Treatment with radiotherapy for the target lesion within 4 weeks before the first administration of the investigational drug, or accepted any anti-tumor drugs/ treatments (including but not limited to chemotherapy, targeted therapy, immunotherapy) within 5 half-lives before the first administration of the investigational drug, whichever is longer; or patients who have received herbal therapies with anti-tumor indications within 1 week before the first administration.
• Primary central nervous system (CNS) tumor or CNS metastasis at screening. The following patients can be considered for enrollment: after treatment and being stable for ≥ 3 months, patients who have completed the treatment at least 10 days before the start of the study treatment; the corticosteroid treatment has been terminated for ≥ 5 days when the study treatment starts, the neurological function is stable, and it is estimated that no steroids or antiepileptic drugs will be required during the study treatment.
• Patients judged by the investigator to have uncontrolled pleural effusion, pericardial effusion, or peritoneal effusion (requiring repeated drainage, multiple times a month or more frequently) at screening. Allow patients to indwell catheters regardless of drainage frequency.
• Patients with untreated or clinically symptomatic spinal cord compression that has not been controlled (except for patients who have received treatment and have stable symptoms, whose imaging examination shows that they are stable for at least 4 weeks before the first administration, and who have no evidence of brain edema and do not require glucocorticoid treatment).
• Patients with ≥ 2 malignant tumors within 5 years before the first administration. Except for cured early-stage malignancies (carcinoma in situ or stage I tumor), such as adequately treated cervical carcinoma in situ, basal cell or squamous epithelial cell skin cancer.
• Patients who are found to have active pulmonary tuberculosis infection within 1 year before enrollment through medical history, or those with a history of active pulmonary tuberculosis infection more than one year ago who have not received formal treatment.
• Interstitial lung disease or interstitial pneumonia, including clinically significant radiation pneumonia (i.e., affecting activities of daily living or requiring intervention).
• Severe infection within 4 weeks before the first administration, including but not limited to bacteremia and severe pneumonia, etc. requiring hospitalization; CTCAE ≥ grade 2 active infection requiring systemic antibiotic treatment within 2 weeks before the first administration.
• History of serious cardiovascular and cerebrovascular diseases, including but not limited to serious cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention, degree II-III atrioventricular block, etc.; acute coronary syndrome, congestive cardiac failure, aortic dissection, stroke or other grade 3 or above cardiovascular and cerebrovascular events within 6 months before the first administration; New York Heart Association (NYHA) cardiac function classification (see appendix 5) ≥ grade II or left ventricular ejection fraction (LVEF)\<50% or hypertension that cannot be clinically controlled (systolic blood pressure ≥ 150 mmHg, diastolic blood pressure ≥ 100 mmHg).

Sponsors & Collaborators

• CytosinLab Therapeutics Co., Ltd.: lead

Study Sites (2)

The First Affiliated Hospital of Henan University of Science and Technology

Luoyang, Henan, 471000, China

RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms; Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Wu H P, Docotor

  CytosinLab Therapeutics Co., Ltd.

  STUDY CHAIR

Central Study Contacts

Xing S N, Master

CONTACT

13816824670; shuning.xing@cytosinlab.com

Song Z B, Docotor

CONTACT

13857153345; songzb@zjcc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: QD and durg holiday,PO.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: QD and durg holiday,PO.

Study Record Dates

• First Submitted: May 7, 2023
• First Posted: January 25, 2024
• Study Start: June 26, 2023
• Primary Completion: July 31, 2025
• Study Completion: October 31, 2025
• Last Updated: August 23, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)