Clinical trial NCT06245122: A Study of CS23546 in Subjects With Advanced Tumors
Official title: A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of CS23546 in Subjects With Advanced Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Tumors
Lead sponsor: Chipscreen Biosciences, Ltd.
Sponsor class: INDUSTRY
First posted: 2024-02-07
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose Limiting Toxicities (DLTs)
timeFrame: Day 1 through Day 27
measure: Maximum Tolerated Dose (MTD)
timeFrame: Day 1 through Day 27
measure: Time to Cmax (Tmax)
timeFrame: up to Day 1 of cycle 5 (each cycle is 21 days)
measure: Maximum plasma concentration (Cmax)
timeFrame: up to Day 1 of cycle 5 (each cycle is 21 days)
measure: Area Under the Curve (AUC)
timeFrame: up to Day 1 of cycle 5 (each cycle is 21 days)
Secondary outcomes:
measure: The inhibitory activity of Programmed cell death 1 ligand 1 (PD-L1)
timeFrame: up to Day 1 of cycle 5 (each cycle is 21 days)
measure: Interferon gamma (IFN-γ)
timeFrame: up to Day 1 of cycle 5 (each cycle is 21 days)
measure: Free PD-L1
timeFrame: up to Day 1 of cycle 5 (each cycle is 21 days)
measure: C-X-C motif chemokine 9 (CXCL9)
timeFrame: up to Day 1 of cycle 5 (each cycle is 21 days)
measure: C-X-C motif chemokine 10 (CXCL10)
timeFrame: up to Day 1 of cycle 5 (each cycle is 21 days)
measure: Objective response rate (ORR)
timeFrame: Until 28 days after the last dose of the study drug
measure: Disease control rate (DCR)
timeFrame: Until 28 days after the last dose of the study drug
measure: Duration of response (DOR)
timeFrame: Until 28 days after the last dose of the study drug
measure: Time to progression (TTP)
timeFrame: Until 28 days after the last dose of the study drug
measure: time to progressive disease (TTR)
timeFrame: Until 28 days after the last dose of the study drug
measure: Progression free survival (PFS)
timeFrame: Until 28 days after the last dose of the study drug
measure: Overall survival (OS)
timeFrame: Until 28 days after the last dose of the study drug
measure: Safety indicators: adverse events (AE)
timeFrame: Until 28 days after the last dose of the study drug
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Cancer
Study officials:
affiliation: Sun Yat-sen University Cancer Cancer
name: Huiqiang Huang, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: