A Multi-center, Open-label, Dose Escalation/Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumor Activity of CTS2190 in Patients With Solid Tumors

CytosinLab Therapeutics Co., Ltd.2 sites in 1 country224 target enrollmentJune 26, 2023

ConditionsSolid Tumors Pancreatic Cancer Non-small Cell Lung Cancer Triple-negative Breast Cancer

InterventionsCTS2190 capsules

Overview

Phase: Phase 1
Intervention: CTS2190 capsules
Conditions: Solid Tumors
Sponsor: CytosinLab Therapeutics Co., Ltd.
Enrollment: 224
Locations: 2
Primary Endpoint: Dose Escalation：The maximum tolerated dose (MTD)
Status: Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Detailed Description

This is a Phase 1/2 multi-center, open label study in solid tumor patients. Phase 1（Part1) is a dose escalation study of oral CTS2190 in patients with solid tumors，which is planned to treat up to 144 participants. Phase 2（Part2) is an open label, dose expansion study in specific tumor types. In both parts of the study, participants who tolerate the drug may continue the treatment until disease progression. The study duration for each subject is defined as beginning from 28 days prior to the first dose, until the subject withdrawal of informed consent, end of treatment, loss to follow-up or death, completes 48 weeks of continuous treatment or the study ends early, whichever occurs first. The end of study is defined as the date when the last subject completes the last visit specified in the protocol.

Registry

clinicaltrials.gov

Start Date

June 26, 2023

End Date

October 31, 2025

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

CytosinLab Therapeutics Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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 \[calculate the creatinine clearance using Cockcroft-Gault formula (appendix 3)\];

Exclusion Criteria

•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).

Arms & Interventions

Dose Escalation/Dose Expansion

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

Intervention: CTS2190 capsules

Outcomes

Primary Outcomes

Dose Escalation：The maximum tolerated dose (MTD)

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

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).

Dose Escalation：The recommended phase 2 dose (RP2D)

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

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.

Dose Expansion：Objective response rate(ORR)

Time Frame: Every 6 weeks for the duration of study participation.

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

Secondary Outcomes

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)
Pharmacokinetic (PK) characteristics：apparent clearance (CL/F)(single-dose stage: Day 1 to Day 4)
Pharmacokinetic (PK) characteristics：apparent volume of distribution (Vz/F)(single-dose stage: Day 1 to Day 4)
Pharmacokinetic (PK) characteristics：mean residence time (MRT)(single-dose stage: Day 1 to Day 4)
Pharmacokinetic (PK) characteristics：accumulation indexes Rac,Cmax and Rac,AUC(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：area under concentration-time curve from time of the last administration to the last detectable concentration (AUC0-t,ss)(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：area under concentration-time curve from time of last administration to infinity (AUC0-∞,ss)(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 steady-state peak concentration (Tmax, ss)(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：steady-state peak concentration (Cmax,ss)(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：steady-state trough concentration (Css trough)(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：steady-state elimination half-life (T1/2, ss)(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：steady-state elimination rate constant (λz,ss)(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：steady-state apparent clearance (CL/F,ss)(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：steady-state apparent volume of distribution (V/F,ss)(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)
Dose Expansion：Objective response rate (ORR)(Every 6 weeks for the duration of study participation)
Incidence of TEAEs and SAEs(Baseline through 28 days after end of treatment, estimated up to 48 weeks)
Duration of response (DOR)(Every 6 weeks for the duration of study participation)
Disease control rate (DCR)(Every 6 weeks for the duration of study participation)
Progression-free survival (PFS)(Every 6 weeks for the duration of study participation)
Pharmacodynamic (PD) characteristics of CTS2190 : asymmetric dimethylarginine (ADMA)(Single-dose stage:Day 1; Multiple-dose stage: Cycle 1 (each cycle is 21 days) Day1, Cycle 1 Day 8, Cycle 1 Day 15 and Cycle 3 Day 1)
Pharmacodynamic (PD) characteristics of CTS2190 : monomethyl arginine (MMA)(Single-dose stage:Day 1; Multiple-dose stage: Cycle 1 (each cycle is 21 days) Day 1, Cycle 1 Day 8, Cycle 1 Day 15 and Cycle 3 Day 1)