Safety, Pharmacokinetics and Preliminary Efficacy of CS231295 in Advanced Solid Tumors

NCT06902350 | Recruiting Phase 1

• 1 other identifier: CS231295-101
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 2

Brief Summary

This trial is a single-arm, open-label, first-in-human study of CS231295, comprising two phases: dose escalation (including single-dose and multiple-dose) and cohort expansion. The Dose-Limiting Toxicity (DLT) observation period includes 6 days for single-dose and the first cycle (28 days) for multiple-dose. The overall study consists of screening period, treatment period, and follow-up period. The primary objectives of this study are to evaluate the safety, tolerability and pharmacokinetic (PK) characteristics of CS231295 in patients with advanced solid tumors, and to recommended Phase 2 dose(s) (RP2D) of CS231295 in appropriate tumor(s).

Conditions

Neoplasms; Glioblastoma, Adult; Small Cell Lung Carcinoma (SCLC)

Outcome Measures

Primary Outcomes (11)

• incidence of dose-limiting toxicity (DLT)

  34 days after, that is 6 days after single-dose and 28 days after first administration in multiple-dose

• maximum tolerated dose (MTD)

  dose escalation part, about 2 years

• incidence of adverse events (AEs)

  Number of participants with AE(s)

  from first administration to 28 days after last administration or next anti-tumor therapy, whichever occurs first

• Pharmacokinetic parameters: Time to Maximum Concentration (Tmax)

  during treatment, up to 11 cycles, 28 days in one cycle

• Pharmacokinetic parameters: Maximum Concentration (Cmax)

  during treatment, up to 11 cycles, 28 days in one cycle

• Pharmacokinetic parameters: Area Under the Concentration-time Curve(AUC)

  during treatment, up to 11 cycles, 28 days in one cycle

• Pharmacokinetic parameters: Trough Concentration (Ctrough)

  during treatment, up to 11 cycles, 28 days in one cycle

• Pharmacokinetic parameters: Accumulation Ratio (Rac)

  during treatment, up to 11 cycles, 28 days in one cycle

• Pharmacokinetic parameters: Elimination Half-life (t1/2)

  during treatment, up to 11 cycles, 28 days in one cycle

• Pharmacokinetic parameters: Clearance over Fractional Bioavailability (CL/F)

  during treatment, up to 11 cycles, 28 days in one cycle

• Pharmacokinetic parameters: Volume of Distribution at Steady State over Fractional Bioavailability (Vz/F)

  during treatment, up to 11 cycles, 28 days in one cycle

Secondary Outcomes (7)

• Objective Response Rate (ORR)

  during study, expected average one year

• Disease control rate (DCR)

  during study, expected average one year

• Duration of Response (DOR)

  during study, expected average one year

• Time to Progression (TTP)

  during study, expected average one year

• Time to Response (TTR)

  during study, expected average one year

Study Arms (1)

CS231295

EXPERIMENTAL

two phases: dose escalation and cohort expansion. The dose escalation part is further divided into single-dose and multiple-dose administration. In the cohort expansion part, only multiple doses.

Drug: CS231295

Interventions

CS231295 DRUG

oral tablet. Only one dose on C0D1 in single-dose period. Once daily from C1D1 until disease progression, death, intolerable toxicity, loss to follow-up, withdrawal of informed consent, or the end of the trial, whichever occurs first, in multiple-dose period in both escalation and cohort expansion phases.

CS231295

Eligibility Criteria

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

You may qualify if:

• Understand and sign the informed consent form voluntarily.
• ≥18 years old when signing the informed consent, regardless of sex.
• Have histologically or cytologically confirmed unresectable advanced, recurrent, or metastatic solid tumors (including but not limited to small cell lung cancer, glioblastoma, urothelial carcinoma, endometrial cancer, cervical cancer, ovarian cancer, breast cancer, and liver cancer) for which standard therapy has failed or was intolerable, and currently no standard treatment is available.
• Radiological or histopathological evidence indicating disease progression should be documented.
• Intolerance is defined as discontinuation of treatment due to adverse events during therapy.
• Recurrence is based on radiological or histopathological results.
• For glioblastoma: at least one measurable intracranial tumor lesion according to the RANO 2.0 criteria. For other solid tumors: at least one measurable lesion according to RECIST v1.1 criteria. Note: Target lesions can be located in previously irradiated areas, but must be confirmed by imaging to show disease progression after radiation.
• For glioblastoma: KPS score ≥60. For other solid tumors: ECOG performance status of 0 or 1.
• Meet the following laboratory criteria (without receiving any blood products, hematopoietic growth factors, albumin, or other treatments within 14 days prior to testing, except iron supplements):
• Hematology: Hemoglobin (Hb) ≥100 g/L, absolute neutrophil count (ANC) ≥1.5×10\^9/L, platelet (PLT) count ≥100×10\^9/L.
• Biochemistry: 1) Dose escalation phase: Serum creatinine (Cr) ≤ upper limit of normal (ULN); total bilirubin (TBIL) ≤1.25×ULN; alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤1.5×ULN (for subjects with liver metastases or hepatocellular carcinoma: ≤3×ULN). 2) Cohort expansion phase: Cr ≤1.5×ULN; TBIL ≤1.5×ULN; ALT, AST ≤2.5×ULN (for subjects with liver metastases or hepatocellular carcinoma: ≤5×ULN).
• Coagulation: International normalized ratio (INR) ≤1.5×ULN; prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤1.5×ULN (for participants receiving prophylactic anticoagulation, the INR and APTT should be within a safe and effective therapeutic range as judged by the investigator).
• Urinalysis: Urine protein \<2+; if ≥2+, a 24-hour urine protein quantification should be performed. \<1 g/24 h can be enrolled but ≥1 g/24 h is prohibited. without quantification when urine protein ≥2+ is not allowed.
• Expected survival ≥12 weeks.
• Cohort Expansion Phase: 1) Cohort 1: Histologically or cytologically confirmed small cell lung cancer (SCLC) that has progressed or recurred after at least two lines of systemic chemotherapy (including a platinum-based regimen). Note: A new line of treatment is defined as a change in treatment due to disease progression, not due to toxicity or other reasons. Re-initiation of the same treatment regimen after initial progression is considered a new line of treatment. 2) Cohort 2: Recurrent or progressive glioblastoma confirmed by histopathology or imaging, which has progressed or recurred after at least one prior treatment with temozolomide.

You may not qualify if:

• Received any form of intracranial radiotherapy within 3 months prior to the first dose.
• Previously received Aurora kinase inhibitors.
• Used strong inducers or inhibitors of cytochrome P450 3A (CYP3A) enzymes within 14 days prior to the first dose or are still within 7 half-lives of such drugs (whichever is longer).
• For glioblastoma only: \>5 mg/day dexamethasone or equivalent doses of other glucocorticoids for systemic treatment related to glioblastoma within 1 week prior to the first dose.
• Underwent major surgery (cranial, thoracic, or abdominal) within 28 days prior to the first dose or have unresolved wounds, ulcers, or fractures as judged by the investigator at screening.
• Have unresolved toxicities from previous treatments that have not recovered to CTCAE v5.0 grade ≤1, except for alopecia or laboratory abnormalities deemed no clinical significant by the investigator.
• History of other primary malignancies within 5 years prior to the first dose, except for adequately treated in situ carcinoma, non-melanoma skin cancer, or malignant melanosis.
• For solid tumors other than glioblastoma: Unstable brain metastases. Stable brain metastases are allowed if:
• No immediate or planned local treatment for brain metastases during the study.
• No neurological symptoms or signs (e.g., increased intracranial pressure, seizures, cognitive impairment) at screening.
• Brain lesions stable for ≥2 weeks prior to the first dose without corticosteroid or anticonvulsant treatment.
• Leptomeningeal metastasis (except glioblastoma).
• Severe brain herniation or risk thereof.
• For glioblastoma only: who had wafer(s) implantation during surgery.
• Received drainage of pleural effusion, ascites, or pericardial effusion within 1 month prior to the first dose or have significant clinical symptoms (e.g., chest tightness, shortness of breath, dyspnea).

Sponsors & Collaborators

• Chipscreen Biosciences, Ltd.: lead

Study Sites (2)

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100070, China

NOT YET RECRUITING

Jilin Cancer Hospital

Changchun, Jilin, 130103, China

RECRUITING

MeSH Terms

Conditions

Neoplasms; Glioblastoma; Small Cell Lung Carcinoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Wenbin Li, M.D.

  Beijing Tiantan Hospital

  PRINCIPAL INVESTIGATOR

• Ying Cheng, M.D.

  Jilin Provincial Tumor Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xinhang Wang

CONTACT

+86 0755-36993500; xinhwang@chipscreen.com

Study Design

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

Study Record Dates

• First Submitted: March 17, 2025
• First Posted: March 30, 2025
• Study Start: May 21, 2025
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2029
• Last Updated: May 25, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)