A Clinical Study of Purinostat Mesylate for Injection in Patients With Advanced Solid Tumors

NCT06431243 | Recruiting Phase 1

• 1 other identifier: ZLPM-003-1.0
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 2

Brief Summary

Primary Objectives Phase Ib To evaluate the safety and tolerability of Purinostat Mesylate in combination therapy for advanced solid tumors; and to explore the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of Purinostat Mesylate in combination therapy in patients with advanced solid tumors. To determine the recommended Phase II dose (RP2D) of Purinostat Mesylate in combination therapy for advanced solid tumors. Phase IIa To further evaluate the preliminary efficacy of Purinostat Mesylate in combination therapy in patients with advanced solid tumors. Secondary Objectives Phase Ib To evaluate the safety and tolerability of Purinostat Mesylate Monotherapy for the treatment of advanced solid tumors; To evaluate the preliminary efficacy of Purinostat Mesylate in combination therapy in patients with advanced solid tumors; To evaluate the pharmacokinetic characteristics of Purinostat Mesylate in combination therapy for the treatment of advanced solid tumors. Phase IIa To further evaluate the safety and tolerability of Purinostat Mesylate in combination therapy for advanced solid tumors. To evaluate the pharmacokinetic characteristics of Purinostat Mesylate in combination therapy for advanced solid tumors. Exploratory Objectives To assess the pharmacodynamic characteristics in Purinostat Mesylate combination therapy for advanced solid tumors.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (1)

• Objective remission rate (ORR)

  defined as the proportion of subjects with an overall efficacy response of complete remission (CR) or partial remission (PR) after at least one post-baseline evaluation during the trial.

  Up to week 96

Secondary Outcomes (6)

• Complete Remission Rate (CRR)

  Up to week 96

• Disease Control Rate (DCR)

  Up to week 96

• Duration of remission (DOR)

  Up to week 96

• Time to Tumor Remission (TTR)

  Up to week 96

• Progression-free survival (PFS)

  Up to week 96

Study Arms (4)

A0 group

EXPERIMENTAL

Cohort A0 is for patients with locally advanced or metastatic breast cancer treated with PM. The cohort doses are escalated in the order of 11.2 mg/m2, 15.0 mg/m2, and XX mg/m2 (if the SMC assesses that there are safety risks in the monotherapy escalation starting dose group, it can be reduced to 8.4 mg/m2 or a dose determined by the SMC). In Cohort A0, subjects in the dose-escalation group all receive PM intravenous infusion on days 1, 4, 15, and 18 of each cycle, with a 28-day cycle (within the same dosing cycle, the interval between two doses is at least ≥48 h), and the maximum duration of dosing does not exceed 96 weeks.

Drug: A0/B0 group Purinostat Mesylate 11.2mg/m2; Drug: A0/B0 group Purinostat Mesylate 15mg/m2

A group

EXPERIMENTAL

Cohort A is for patients with HR+/HER2- (hormone receptor positive/human epidermal growth factor receptor 2 negative) advanced breast cancer treated with PM in combination with fulvestrant. In Cohort A, subjects in the dose-escalation group all receive PM intravenous infusion on days 1, 4, 15, and 18 of each cycle, with a 28-day cycle (within the same dosing cycle, the interval between two doses is at least ≥48 h); fulvestrant (FS) is administered as two 5 mL injections slowly into the buttocks on days 1 and 15 of the first cycle, with one injection per buttock (1-2 minutes/5 mL), and starting from the second cycle, 500 mg (specification 5 mL: 0.25 g) is given once on the first day of each cycle (CnD1), with a 28-day cycle. Based on the results obtained in the dose-escalation phase, the necessity of the Phase IIa expansion cohort and the dosing of PM will be determined by the SMC after discussion.

Drug: A group Purinostat Mesylate 6mg/m2; Drug: A group Purinostat Mesylate 8.4mg/m2; Drug: A group Purinostat Mesylate 11.2mg/m2; Drug: A group Purinostat Mesylate 15 mg/m2

B0 group

EXPERIMENTAL

Cohort B0 is for patients with advanced solid tumors treated with PM. The cohort doses are escalated in the order of 11.2 mg/m2, 15.0 mg/m2, and XX mg/m2 (if the SMC assesses that there are safety risks in the monotherapy escalation starting dose group, it can be reduced to 8.4 mg/m2 or a dose determined by the SMC). In Cohort B0, subjects in the dose-escalation group all receive PM intravenous infusion, with a dosing frequency of BiW (twice weekly), for continuous dosing over 2 weeks, that is, on days 1, 4, 8, and 11 of each cycle, with a 21-day cycle (within the same dosing cycle, the interval between two doses is at least ≥48 h), and the maximum duration of dosing does not exceed 96 weeks.

Drug: A0/B0 group Purinostat Mesylate 11.2mg/m2; Drug: A0/B0 group Purinostat Mesylate 15mg/m2

B group

EXPERIMENTAL

Cohort B is for patients with advanced solid tumors treated with PM in combination with tislelizumab. In Cohort B, subjects in the dose-escalation group all receive PM intravenous infusion on days 1, 4, and 8 of each cycle, with a 21-day cycle (within the same dosing cycle, the interval between two doses is at least ≥48 h). Tislelizumab is administered as a 200 mg intravenous infusion, once every 3 weeks, on the first day of each cycle. Based on the results obtained in the dose-escalation phase, the necessity of the Phase IIa expansion cohort and the dosing will be determined by the Safety Monitoring Committee (SMC) after discussion.

Drug: B group Purinostat Mesylate 6 mg/m2; Drug: B group Purinostat Mesylate 8.4 mg/m2; Drug: B group Purinostat Mesylate 11.2mg/m2; Drug: B group Purinostat Mesylate 15mg/m2

Interventions

A0/B0 group Purinostat Mesylate 11.2mg/m2 DRUG

Purinostat Mesylate 11.2mg/m2

A0 group; B0 group

A0/B0 group Purinostat Mesylate 15mg/m2 DRUG

Purinostat Mesylate 15mg/m2

A0 group; B0 group

A group Purinostat Mesylate 6mg/m2 DRUG

Purinostat Mesylate 6mg/m2 + FS 500mg

A group

A group Purinostat Mesylate 8.4mg/m2 DRUG

Purinostat Mesylate 8.4mg/m2 + FS 500mg

A group

A group Purinostat Mesylate 11.2mg/m2 DRUG

Purinostat Mesylate 11.2mg/m2 + FS 500mg

A group

A group Purinostat Mesylate 15 mg/m2 DRUG

Purinostat Mesylate 15 mg/m2 + FS 500mg

A group

B group Purinostat Mesylate 6 mg/m2 DRUG

Purinostat Mesylate 6mg/m2 + Tislelizumab 200mg

B group

B group Purinostat Mesylate 8.4 mg/m2 DRUG

Purinostat Mesylate 8.4mg/m2 + Tislelizumab 200mg

B group

B group Purinostat Mesylate 11.2mg/m2 DRUG

Purinostat Mesylate 11.2mg/m2 + Tislelizumab 200mg

B group

B group Purinostat Mesylate 15mg/m2 DRUG

Purinostat Mesylate 15mg/m2 + Tislelizumab 200mg

B group

Eligibility Criteria

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

You may qualify if:

• Age: ≥18 years and ≤75 years, regardless of gender.
• At least one measurable lesion as defined by RECIST 1.1 during the screening period (for the breast cancer cohort in the dose-escalation phase, measurable lesions are not required if the participant has only bone metastases).
• Phase Ib:
• Monotherapy Dose-Escalation Phase:
• Monotherapy in Cohort A0 (Breast Cancer):
• Histologically or cytologically confirmed locally advanced or metastatic breast cancer that has failed standard treatment, for which no standard treatment is available, or for which standard treatment is not suitable at the current stage.
• Monotherapy in Cohort B0 (Solid Tumors):
• Histologically or cytologically confirmed locally advanced or metastatic solid tumors that have failed standard treatment, for which no standard treatment is available, or for which standard treatment is not suitable at the current stage. This includes but is not limited to triple-negative breast cancer, colorectal cancer, and urothelial cancer.
• Combination Therapy Dose-Escalation Phase:
• Combination with Fulvestrant in Cohort A (Breast Cancer):
• Histologically or cytologically confirmed breast cancer in perimenopausal, premenopausal, or postmenopausal women with estrogen receptor (ER)-positive, progesterone receptor (PgR)-negative or positive, and non-HER2-positive (including HER2-negative and low-expression) disease.
• Participants must have progressed or recurred after at least one line of endocrine therapy (regardless of whether it was in the advanced, metastatic, or neoadjuvant chemotherapy setting), with up to two lines of prior chemotherapy allowed.
• Ineligible for surgical resection.
• Definition of menopause must meet one of the following criteria:
• Previous bilateral oophorectomy;

You may not qualify if:

• Participants who meet any of the following criteria are not eligible for the trial:
• Known severe allergy to the investigational drug, any of the combination drugs, or any of their excipients (hydroxypropyl-beta-cyclodextrin, arginine, tromethamine, mannitol).
• Presence or history of other malignancies (except adequately treated basal cell carcinoma or squamous cell carcinoma of the skin, or cervical carcinoma in situ), unless the participant has undergone curative treatment and has evidence of no recurrence or metastasis within the past 5 years.
• Symptomatic central nervous system (CNS) metastases or CNS metastases requiring corticosteroid treatment within 2 weeks before the first dose of the study drug. Participants with asymptomatic CNS metastases are also excluded. Participants with leptomeningeal carcinomatosis or meningeal dissemination are excluded.
• Participants with a history of anti-tumor treatment meeting the following criteria must be excluded:
• Received mitomycin C or nitrosourea chemotherapy (e.g., carmustine, lomustine) within 6 weeks before the first dose.
• Received systemic anti-tumor treatment (e.g., chemotherapy, endocrine therapy, immunotherapy, biological therapy) within 4 weeks before the first dose.
• Received investigational drug treatment in a clinical trial or is currently participating in another clinical trial within 4 weeks before the first dose.
• Received oral fluoropyrimidine or small-molecule targeted therapy within 2 weeks before the first dose or within 5 half-lives of the known drug (whichever is longer).
• Received palliative local radiotherapy within 2 weeks before the first dose.
• Received traditional Chinese medicine or patent Chinese medicine with anti-tumor indications within 2 weeks before the first dose.
• Note: If a participant has received multiple treatments with different washout periods, the actual washout period will be determined by the longer duration.
• Participants who have previously received HDAC inhibitors.
• Participants who have previously received any estrogen receptor degraders, including but not limited to fulvestrant, are not eligible for the cohort combining with fulvestrant.
• Participants who have previously received anti-PD-1/PD-L1 antibody treatment are not eligible for the cohort combining with tislelizumab, unless the participant has previously benefited from anti-PD-1/PD-L1 treatment in the advanced/metastatic setting and may be included.

Sponsors & Collaborators

• Chengdu Zenitar Biomedical Technology Co., Ltd: lead

Study Sites (2)

Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Guanzhou, Guangzhou, 510000, China

RECRUITING

West China hospital of Sichuan university

Chengdu, Sichuan, 610000, China

RECRUITING

Study Officials

• Herui Yao, Doctor

  Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

• Yongsheng Wang, Doctor

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Liangkun Sun, bachelor

CONTACT

15885742617; liangkunsun@zenitar.cn

Zheng Jiang, bachelor

CONTACT

19048075294; zhengjiang@zenitar.cn

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: May 20, 2024
• First Posted: May 28, 2024
• Study Start: May 8, 2024
• Primary Completion: May 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: April 10, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)