A Phase I/II Study of AST-3424 in Subjects With Advanced Solid Tumors

NCT06239155 | Active Not Recruiting Phase 1

• 1 other identifier: AST-3424-001
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 7

Brief Summary

An open-label, Phase I/II study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of AST-3424 administered as a single agent

Conditions

Advanced Solid Tumors; Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (14)

• Incidence and severity of adverse events(AEs)

  Adverse events will be noted and graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0 or severity (if not covered by CTCAE)

  measure begins from informed consent to 30 days after last dose of study drug.

• Safety changes in electrocardiogram (ECG)

  Resting 12-lead ECGs will be obtained from all subjects' pre-AST-3424 infusion and within 30 minutes post-AST-3424 infusion in order to assess any impact AST-3424 may have on the QT interval as assessed by the Fridericia's Correction Formula (QTcF).

  Day 1 Cycles 1 and 2 (each cycle is 21 days)

• Safety Changes of body weight

  If during treatment a participant's body weight changes by \>10%, the dose should be adjusted.

  Day 1 of each cycle (there are 34 cycles; 21 days for each cycle)

• Dose limiting toxicities (DLTs) in phase I

  Number of participants with dose limiting toxicities (DLTs)

  Throughout Cycle 1 (21 days for each cycle) in phase I (dose escalation phase).

• Maximum Tolerated Dose(MTD)/Recommended Phase 2 Dose (RP2D) in phase I

  Determination of the MTD, based on the frequently of DLTs observed in Cycle 1 in participants enrolled to the Dose Escalation Phase.

  Day 1 and Day 8 of each cycle (all 34 cycles and there are 21 days for each cycle)

• Pharmacokinetics (PK) - Time to maximum concentration (Tmax)

  Tmax of AST-3424 and AST-2660 will be computed for each subject where possible.

  Days 1 and 8 of Cycle 1 (first cycle of 34 cycles and there are 21 days for each cycle)

• PK - Maximum peak plasma concentration (Cmax)

  Cmax of AST-3424 and AST-2660 will be computed for each subject where possible.

  Days 1 and 8 of Cycle 1 (first cycle of 34 cycles and there are 21 days for each cycle)

• PK - The magnitude of the slope of the linear regression of the log concentration vs. time profile during the terminal phase (Kel)

  Kel of AST-3424 and AST-2660 will be computed for each subject where possible.

  Days 1 and 8 of Cycle 1 (first cycle of 34 cycles and there are 21 days for each cycle)

• PK - Half-life (T1/2)

  T1/2 computed as ln (2)/Kel of AST-3424 and AST-2660 will be computed for each subject where possible.

  Days 1 and 8 of Cycle 1 (first cycle of 34 cycles and there are 21 days for each cycle)

• PK - Area under the concentration-time curve (AUClast)

  AUClast from Hour 0 through the last quantifiable concentration time (LQCT), where LQCT is the time at which the last sample with a quantifiable concentration was drawn

  Days 1 and 8 of Cycle 1(first cycle of 34 cycles and there are 21 days for each cycle)

• Objective response rate(ORR)

  Approximately 36 months

• Disease control rate(DCR)

  Approximately 36 months

• Duration of response (DOR)

  Approximately 36 months

• Progress free survival (PFS)

  Approximately 36 months

Study Arms (2)

Phase I: dose escalation phase

EXPERIMENTAL

AST-3424 (1.0 mg/m\^2 to 10.0 mg/m\^2 or higher doses) will be administered by IV infusion on Day1 and Day8 of each 21-day cycle. 1mg/m\^2 and 2mg/m\^2 cohort will enroll 1 participant respectively . 4mg/m\^2 or higher dose cohorts will use 3+3 dose escalation design to determine the MTD and RP2D.

Drug: AST-3424

Phase II: cohort expansion phase

EXPERIMENTAL

6mg/m\^2, administrated on Day1 and Day 8 of each 21-day cycle

Drug: AST-3424

Interventions

AST-3424 DRUG

liquid formulation for Intravenous infusion

Phase I: dose escalation phase; Phase II: cohort expansion phase

Eligibility Criteria

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

You may qualify if:

• phase I: dose escalation phase
• Male or female, 18-70 years old.
• Histologically and/or cytologically confirmed malignant solid tumors (including but not limited to hepatocellular carcinoma, intrahepatic cholangiocarcinoma, gastric cancer, esophageal cancer, colorectal cancer, pancreatic cancer, renal cell carcinoma, non-small cell lung cancer, and castration-resistant prostate cancer) that are metastatic or unresectable and have failed standard treatment or no standard treatment, pr not suitable for standard treatment at this stage.
• Once MTD is confirmed, participant in the Extended Dose group (MTD group) need to have at least one measurable lesion that meets the RECIST 1.1 criteria. Previously irradiated lesions are not measurable unless they show clear radiographic progression after radiotherapy.
• The physical status score of the Eastern Cancer Collaboration Group (ECOG) is 0 or 1.
• Life expectancy≥12 weeks.
• All toxicities (except alopecia, fatigue, or peripheral neuropathy) from previous anticancer therapy must have returned to grade 1 or baseline levels prior to initiation of the investigational drug (NCI CTCAE 5th Edition).
• The heart QTcF interval ≤450 ms in males or ≤ 470 ms in females.
• Laboratory tests must meet the following criteria. the indicators could not be corrected by blood transfusion or hematopoietic stimulating factors for 14 days prior to the screening laboratory examination.
• Hemoglobin ≥90 g/L
• Platelet count ≥100 x 10\^9/L
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L
• Total bilirubin ≤ 1.5 x upper limit of normal(ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0× ULN, ≤ 5.0× ULN for liver tumors
• Creatinine clearance was \> 50 mL/min according to Cockcroft-Gault formula

You may not qualify if:

• phase I: dose escalation phase
• Untreated active central nervous system (CNS) metastases or leptomeningeal disease. Participant may participate in the study if their CNS metastases have been adequately treated and are stable for at least 4 weeks as confirmed by clinical examination and brain imaging (MRI or CT) during screening.
• Major surgery other than diagnostic surgery was performed within 4 weeks prior to initial dosing.
• Radiotherapy, surgery, chemotherapy, immunotherapy, cancer biotherapy, targeted therapy, or hormonal therapy within 4 weeks prior to the first dose (lomustine or mitomycin C treatment, requiring a 6-week washout period; Oral fluorouracil, requiring a 2-week washout period; Small molecule targeted therapy requires a 2-week washout period).
• Participated in an investigational drug (diagnostic or therapeutic) or device study within 4 weeks prior to initial dosing.
• Combined use of strong potent CYP3A4 inhibitors or inducers need to be used during the study.
• Uncontrolled, active bacterial, viral or fungal infections requiring systemic treatment.
• Known to be positive for human immunodeficiency virus (HIV) or syphilis.
• Women who are pregnant, breast-feeding, or planning to become pregnant.
• Concomitant diseases or symptoms that may interfere with the conduct of the study, or physical abnormalities that the investigator believes pose an excessive risk to the patient, including but not limited to active peptic ulcer or gastritis, changes in mental status, or mental abnormalities that may interfere with the patient's understanding of the informed consent form.
• Previous allergies to ethanol and propylene glycol.
• Unwilling or unable to comply with the study protocol for any reason.
• phase II: cohort expansion phase
• Untreated active central nervous system (CNS) metastases or leptomeningeal disease. Participant may participate in the study if their CNS metastases have been adequately treated and are stable for at least 4 weeks as confirmed by clinical examination and brain imaging (MRI or CT) during screening.
• A history of other malignancies within 2 years, except adequately treated basal cell carcinoma, carcinoma in situ at other sites, or other tumors whose natural history and treatment would not interfere with the evaluation of the safety and efficacy of the study.

Sponsors & Collaborators

• Ascentawits Pharmaceuticals, Ltd: lead

Study Sites (7)

Guangdong Qifu Hospital

Guangzhou, Guangdong, 510000, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450000, China

Location

Chinese People's Liberation Army Eastern Theater General Hospital Qinhuai medical District

Nanjing, Jiangsu, 210000, China

Location

The First Affiliated Hospital of China Medical University

Shenyang, Liaoning, 110000, China

Location

Shanghai East Hospital

Shanghai, Shanghai Municipality, 200000, China

Location

Sir Run Run Shaw Hospital (SRRSH), affiliated with the Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310000, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Jin Li

  Shanghai East Hospital

  PRINCIPAL INVESTIGATOR

• Shukui Qin

  Chinese People's Liberation Army Eastern Theater General Hospital Qinhuai medical District

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 16, 2024
• First Posted: February 2, 2024
• Study Start: September 3, 2019
• Primary Completion: November 30, 2025
• Study Completion: November 30, 2025
• Last Updated: February 25, 2025

Record last verified: 2025-02

Locations

CN (7)