A Study to Evaluate the Activity, Safety and Tolerability of ZX-101A in Advanced Solid Tumors

NCT05258266 | Unknown Phase 1 DMC

• 1 other identifier: ZX-101A-201
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

ZX-101A-201 is a phase I, open-label, multicenter study which includes dose escalation and dose expansion of ZX-101A. It is designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamic (PD), and antitumor activity of ZX-101A in patients with advanced solid tumors.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Defining the RP2D of ZX-101A

  To assess number of patients experiencing dose-limiting toxicities (DLTs)

  From Day 1 of Cycle 1 until 28 days after the last dose (up to 2 years). Each cycle is 28 days.

• To examine the incidence of clinical and laboratory adverse events after multiple doses of ZX-101A

  Incidence of treatment-emergent adverse events \[safety and tolerability\]

  From Day 1 of Cycle 1 until 28 days after the last dose (up to 2 years). Each cycle is 28 days.

Secondary Outcomes (9)

• Objective response rate (ORR)

  Up to 2 years

• Duration of response (DoR)

  Up to 2 years

• Progression free survival (PFS)

  Up to 2 years

• Disease control rate (DCR)

  Up to 2 years

• Overall survival (OS)

  Up to 2 years

Study Arms (5)

ZX-101A Dose Level A

EXPERIMENTAL

ZX-101A administered orally at level A once daily in a 28-day cycle

Drug: ZX-101A

ZX-101A Dose Level B

EXPERIMENTAL

ZX-101A administered orally at level B once daily in a 28-day cycle

Drug: ZX-101A

ZX-101A Dose Level C

EXPERIMENTAL

ZX-101A administered orally at level C once daily in a 28-day cycle

Drug: ZX-101A

ZX-101A Dose Level D

EXPERIMENTAL

ZX-101A administered orally at level D once daily in a 28-day cycle

Drug: ZX-101A

ZX-101A Dose Level E

EXPERIMENTAL

ZX-101A administered orally at level E once daily in a 28-day cycle

Drug: ZX-101A

Interventions

ZX-101A DRUG

Q.D., oral dosing

ZX-101A Dose Level A; ZX-101A Dose Level B; ZX-101A Dose Level C; ZX-101A Dose Level D; ZX-101A Dose Level E

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females who are 18 to 75 years old.
• Minimum life expectancy ≥ 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Histologically or cytologically confirmed inoperable solid tumor subjects and failed standard treatment (PD during treatment or PD after last treatment), or subjects with advanced solid tumors or who cannot tolerate standard treatment and/or currently have no effective standard treatment.
• At least one measurable tumor lesion (according to RECIST V1.1 criteria).
• Systemic chemotherapy has been completed for at least 4 weeks (if the chemotherapy drugs are nitrosoureas and mitomycin C, it should be at least 6 weeks from the last chemotherapy); the anti-tumor monoclonal antibody treatment has been completed at least 4 weeks; small molecule targeted therapy has been completed at least 2 weeks or 5 half-lives of the drug (whichever is longer); Alternative treatment approved by the National Medical Products Administration (NMPA) has been completed for at least 4 weeks.
• Prior to the first dosing, radiotherapy has been completed for at least 4 weeks, local palliative radiotherapy has been completed for at least 2 weeks, and the acute toxicity caused by previous radiotherapy has recovered to ≤ grade 1.
• Prior cell or gene therapy was completed for at least 4 weeks before the first dose of study drug.
• Acceptable baseline assessment: 1) absolute neutrophil count (ANC) ≥1500 /mm3, platelet count (PLT)≥100K /mm3, and hemoglobin (Hb) ≥90 g/L for blood system (no blood transfusion and blood products or hematopoietic stimulating factor therapy within 14 day); 2) total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN) (≤3.0 × ULN in patients with Gilbert syndrome or liver metastases), alanine aminotransferase (ALT) ≤3.0×ULN, aspartate aminotransferase (AST) ≤3.0×ULN, and albumin ≥2.8 g/dL for liver function; 3) creatinine ≤1.5×ULN or creatinine clearance (Ccr) ≥50 ml/min (calculated according to Cockcroft-Gault formula, Ccr is calculated only when creatinine\>1.5×ULN) for kidney function; 4) activated partial thromboplastin time (APTT) ≤1.5×ULN and international normalized ratio (INR) or prothrombin time (PT) ≤1.5×ULN for coagulation.
• Adverse reactions caused by previous treatment recovered to NCI-CTCAE V5.0 standard grade ≤1 before enrollment.
• Female subjects of childbearing age have negative serum pregnancy test results and agree to use effective contraception during the use of the study drug and within 6 months after the last dose.
• Men must agree to no sperm donations during the study and for 3 months after the last dose.
• Be able to understand the requirements of the study, willing to comply with all study procedures and sign the Institutional Review Board (IRB)-approved informed consent.

You may not qualify if:

• Previous use of PI3K δ/γ dual inhibitors.
• Received any anti-infective vaccine within 4 weeks before the first study drug.
• Received investigational study drug within 4 weeks or 5 half-lives, whichever is longer.
• History of other malignancy within the past 5 years, unless cured by surgery and sustained disease-free survival.
• Active autoimmune disease
• Have used systemic corticosteroids within 2 weeks before the first dosing.
• Serious medical conditions, including serious heart disease, uncontrolled diabetes, uncontrolled hypertension, active peptic ulcer, active bleeding, etc.
• Gastrointestinal dysfunction, including motility or malabsorption syndromes or inflammatory bowel disease which could limit absorption of study drug.
• Using medications that may lead to prolonged QT during the study period (e.g., antiarrhythmic drugs).
• Central nervous system or meningeal metastasis with clinical symptoms assessed by the investigator to be unsuitable for enrollment.
• Symptomatic ascites or pleural effusion or pericardial effusion.
• Current or past interstitial lung disease, hypersensitivity pneumonitis, pulmonary fibrosis, acute lung disease, etc.
• Active infection requiring systemic therapy.
• Active tuberculosis infection, receiving anti-tuberculosis treatment or received anti-tuberculosis treatment within 1 year before screening.
• Hepatitis B surface antigen (HBsAg) positive and HBV-DNA quantification \> detection unit upper limit of normal value (ULN), hepatitis C antibody (HCV-Ab) positive and HCV-RNA quantification \> detection unit upper limit of normal value, anti-human immunodeficiency virus antibody (Anti - HIV) positive, cytomegalovirus (CMV) infection or viremia, and active syphilis (any of the above). Hepatitis B virus subjects who are stable after 2 weeks of treatment (HBV-DNA quantification less than the lower limit of normal) and cured hepatitis C subjects (with known HCV history and with negative HCV RNA polymerase chain reaction \[PCR\] test results \< 6 months prior to the start of ZX-101A administration) can be enrolled. CMV testing is required to confirm no CMV infection before screening.

Sponsors & Collaborators

• Nanjing Zenshine Pharmaceuticals: lead

Study Sites (1)

Beijing Cancer Hospital

Beijing, China

Location

Study Officials

• Xiaolin Qin, Ph.D

  Zenshine Pharmaceutical, Inc.

  STUDY DIRECTOR

Central Study Contacts

Li Luo

CONTACT

+86-15951876049; luoli@zenshine-pharma.com

Shun Yang

CONTACT

yangshun@zenshine-pharma.com

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 27, 2022
• First Posted: February 28, 2022
• Study Start: March 9, 2022
• Primary Completion: June 30, 2023
• Study Completion: April 30, 2024
• Last Updated: March 14, 2022

Record last verified: 2022-02

Locations

CN (1)