A Study of CS23546 in Subjects With Advanced Tumors

Advanced Tumors Clinical Trial

Official title:

A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of CS23546 in Subjects With Advanced Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06245122
• Other study ID #: CS23546-101
• Status: Recruiting
• Phase: Phase 1
• Start date: March 27, 2024
• Est. completion date: May 31, 2027

Study information

• Verified date: April 2024
• Source: Chipscreen Biosciences, Ltd.
• Contact: Xinhao Wang
• Phone: +86 0755-36993550
• Email: xinhwang[@]chipscreen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objectives of this study are to characterize the safety and tolerability of CS23546 and to evaluate the pharmacokinetic (PK) characteristics and recommended phase 2 dose (RP2D) of CS23546 in subjects with advanced tumors.

Description:

This study is a single arm, open phase I trial, consisting of a dose escalation phase (single dose+multiple doses) and a dose expansion phase, accompanied by pharmacokinetic and pharmacokinetic studies. The first visit period (21 days) of single dose and multiple doses during the dose-increasing phase is the DLT observation period.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 156
• Est. completion date: May 31, 2027
• Est. primary completion date: February 28, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

1. Male or female and =18 years of age on day of signing informed consent.

2. Histologically or cytologically confirmed unresectable advanced recurrent/refractory solid tumor or lymphoma that is failure or or intolerant of all standard therapy or for which no standard therapy is available.

3. Individuals are required to provide tumor tissue samples for prospective detection of Programmed cell death 1 ligand 1 (PD-L1) expression and/or Microsatellite instability (MSI) / the DNA mismatch repair (MMR) status. Subjects who cannot be provided during the dose escalation phase will be evaluated by the researchers and sponsors before deciding whether to enroll.

4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

5. Adequate organ function.

6. Life expectancy =12 weeks.

7. Dose expansion phase: Cohort 1, Subjects with urothelial carcinoma. Cohort 2, Subjects with Extranodal NK/T-cell lymphoma (NKTCL). Cohort 3, Subjects with soft tissue sarcoma. Cohort 4, Subjects with PD-L1 expression positive and/or microsatellite-instability-high (MSI-H) / mismatch-repair-deficient (dMMR) advanced solid tumors or lymphoma

Key Exclusion Criteria:

1. Received anti-tumor therapy (including but not limited to chemotherapy, targeted therapy, anti angiogenic therapy, immunotherapy, cell therapy, radiotherapy, tumor embolization, etc.) or experimental drugs/devices that have not been approved for marketing within 28 days before the first medication.

2. History of = Grade 3 immune related Adverse Events (irAEs) or termination of treatment due to irAEs during prior treatment with Programmed death 1 (PD-1) /PD-L1 antibody.

3. Active autoimmune diseases present during the screening period and systemic treatment was received within 2 years before the first medication. Individuals who only require hormone replacement therapy (such as thyroxine, insulin, or physiological corticosteroids used for adrenal or pituitary insufficiency) can be enrolled.

4. Presence of central nervous system metastasis and/or meningeal metastasis.

5. Dose expansion phase: Subjects with solid tumors or lymphoma who have previously received PD-L1 inhibitors and belong to primary resistance.

Related Conditions & MeSH terms

• Advanced Tumors

Intervention

Drug:
• CS23546
Tablets administered orally.

Locations

Country	Name	City	State
China	Sun Yat-sen University Cancer Cancer	Guangzhou

Sponsors (1)

Lead Sponsor	Collaborator
Chipscreen Biosciences, Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicities (DLTs)	DLT: Number of patients experienced any dose limited toxicity. MTD: One level lower than the dose level at which dose escalation was terminated due to DLT reasons.	Day 1 through Day 27
Primary	Maximum Tolerated Dose (MTD)	MTD: One level lower than the dose level at which dose escalation was terminated due to DLT reasons.	Day 1 through Day 27
Primary	Time to Cmax (Tmax)	Time to reach the Cmax for CS23546.	up to Day 1 of cycle 5 (each cycle is 21 days)
Primary	Maximum plasma concentration (Cmax)	Maximum observed plasma concentration for CS23546.	up to Day 1 of cycle 5 (each cycle is 21 days)
Primary	Area Under the Curve (AUC)	Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for CS23546.	up to Day 1 of cycle 5 (each cycle is 21 days)
Secondary	The inhibitory activity of Programmed cell death 1 ligand 1 (PD-L1)		up to Day 1 of cycle 5 (each cycle is 21 days)
Secondary	Interferon gamma (IFN-?)	Plasma concentration for IFN-?.	up to Day 1 of cycle 5 (each cycle is 21 days)
Secondary	Free PD-L1	Plasma concentration for free PD-L1.	up to Day 1 of cycle 5 (each cycle is 21 days)
Secondary	C-X-C motif chemokine 9 (CXCL9)	Plasma concentration for CXCL9.	up to Day 1 of cycle 5 (each cycle is 21 days)
Secondary	C-X-C motif chemokine 10 (CXCL10)	Plasma concentration for CXCL10.	up to Day 1 of cycle 5 (each cycle is 21 days)
Secondary	Objective response rate (ORR)	Efficacy evaluation indicators for research.	Until 28 days after the last dose of the study drug
Secondary	Disease control rate (DCR)	Efficacy evaluation indicators for research.	Until 28 days after the last dose of the study drug
Secondary	Duration of response (DOR)	Efficacy evaluation indicators for research.	Until 28 days after the last dose of the study drug
Secondary	Time to progression (TTP)	Efficacy evaluation indicators for research.	Until 28 days after the last dose of the study drug
Secondary	time to progressive disease (TTR)	Efficacy evaluation indicators for research.	Until 28 days after the last dose of the study drug
Secondary	Progression free survival (PFS)	Efficacy evaluation indicators for research.	Until 28 days after the last dose of the study drug
Secondary	Overall survival (OS)	Efficacy evaluation indicators for research.	Until 28 days after the last dose of the study drug
Secondary	Safety indicators: adverse events (AE)	The incidence and severity of adverse events (AE) (according to CTCAE v5.0).	Until 28 days after the last dose of the study drug