## Protocol Section
### Identification Module
**NCT ID:** NCT06431243

**Brief Title:** A Clinical Study of Puesta Mesylate for Injection in Patients With Solid Tumors

**Official Title:** An Open, Multicenter Phase Ib/IIa Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of the Combination of Puesta Mesylate for Injection in the Treatment of Advanced Solid Tumors

#### Organization Study ID Info
**ID:** ZLPM-003-1.0
#### Organization
**Class:** INDUSTRY
**Full Name:** Chengdu Zenitar Biomedical Technology Co., Ltd
### Status Module
#### Completion Date
**Date:** 2026-11-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-28

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-24

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-05-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-31

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-28
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-20
**Study First Submit QC Date:** 2024-05-24
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Chengdu Zenitar Biomedical Technology Co., Ltd

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** Primary Purpose Phase Ib Evaluate the safety and tolerability of the combination of puesta mesylate in the treatment of advanced solid tumors; and explore the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of the combination of puesta mesylate in patients with advanced solid tumors; Determine the recommended phase II dose (RP2D) for the combination of puesta mesylate in the treatment of advanced solid tumors.

Phase IIa. To further evaluate the preliminary efficacy of the combination of puesta mesylate in patients with advanced solid tumors.

Secondary objective Phase Ib Evaluate the safety and tolerability of poystat mesylate monotherapy in advanced solid tumors; To evaluate the preliminary efficacy of the combination of poystat mesylate in patients with advanced solid tumors; To evaluate the pharmacokinetic profile of the combination of puesta mesylate in the treatment of advanced solid tumors.

Phase IIa To further evaluate the safety and tolerability of the combination of puesta mesylate in the treatment of advanced solid tumors; To evaluate the pharmacokinetic profile of the combination of puesta mesylate in the treatment of advanced solid tumors.

Exploratory Objective. To evaluate the pharmacodynamic significance of biomarkers in the combination of puesta mesylate for the treatment of advanced solid tumors.

### Conditions Module

**Conditions:**

- Advanced Solid Tumor

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 120

**Type:** ESTIMATED

**Phases:**

- PHASE1

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** In Cohort A, subjects in the ascending-dose group received PM IV, administered at a frequency of BiW (2 times per week) for 2 weeks, i.e., on days 1, 4, 8, and 11 of each cycle, with a 1-week discontinuation to allow for a 21-day cycle (with a minimum interval of ≥48 h between each of the 2 doses within the same dosing cycle), and exemestane was administered orally once a day within 30 min after the end of breakfast as one tablet ( 25 mg). Based on the results obtained in the dose-escalation phase, the necessity of the phase IIa expansion cohort and the dose of PM to be administered will be decided after discussion by the SMC, and the phase IIa cohort expansion is expected to select 1-2 dose groups of 10-15 cases each, with a total of 19-54 cases in this cohort

**Intervention Names:**

- 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 15.0mg/m2

**Label:** A group

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** In Cohort B, subjects in the ascending dose group all received PM IV drip administered at a frequency of BiW (2 times per week) for 2 consecutive weeks, i.e., on days 1, 4, 8, and 11 of each cycle, with a 1-week discontinuation for a 21-day cycle (with a minimum interval of ≥48 h between each of the 2 doses in the same dosing cycle). Tirelizumab was administered as 200 mg IV every 3 weeks, administered on the first day of each cycle. Based on the results obtained during the dose-escalation phase, the need for and the dose of the Phase IIa expansion cohort will be determined after discussion by the Safety Management Committee (SMC), and the Phase IIa cohort expansion is expected to select 1-2 dosage groups of 10-15 cases each.

**Intervention Names:**

- Drug: B group Purinostat Mesylate 6.0mg/m2

- Drug: B group Purinostat Mesylate 8.4 mg/m2

- Drug: B group Purinostat Mesylate 11.2 mg/m2

- Drug: B group Purinostat Mesylate 15.0 mg/m2

**Label:** B group

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- A group

**Description:** Purinostat Mesylate 6mg/m2 + EM 25mg

**Name:** A group Purinostat Mesylate 6mg/m2

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- A group

**Description:** Purinostat Mesylate 8.4mg/m2 + EM 25mg

**Name:** A group Purinostat Mesylate 8.4mg/m2

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- A group

**Description:** Purinostat Mesylate 11.2mg/m2 + EM 25mg

**Name:** A group Purinostat Mesylate 11.2mg/m2

**Type:** DRUG

#### Intervention 4

**Arm Group Labels:**

- A group

**Description:** Purinostat Mesylate 15.0mg/m2 + EM 25mg

**Name:** A group Purinostat Mesylate 15.0mg/m2

**Type:** DRUG

#### Intervention 5

**Arm Group Labels:**

- B group

**Description:** Purinostat Mesylate 6.0mg/m2 + Tislelizumab 200mg

**Name:** B group Purinostat Mesylate 6.0mg/m2

**Type:** DRUG

#### Intervention 6

**Arm Group Labels:**

- B group

**Description:** Purinostat Mesylate 8.4mg/m2 + Tislelizumab 200mg

**Name:** B group Purinostat Mesylate 8.4 mg/m2

**Type:** DRUG

#### Intervention 7

**Arm Group Labels:**

- B group

**Description:** Purinostat Mesylate 11.2mg/m2 + Tislelizumab 200mg

**Name:** B group Purinostat Mesylate 11.2 mg/m2

**Type:** DRUG

#### Intervention 8

**Arm Group Labels:**

- B group

**Description:** Purinostat Mesylate 15.0mg/m2 + Tislelizumab 200mg

**Name:** B group Purinostat Mesylate 15.0 mg/m2

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

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

**Measure:** Objective remission rate (ORR)

**Time Frame:** Second cycle Day 30 / Fourth cycle Day 60 / Sixth cycle Day 90 (each cycle is 21 days)

#### Secondary Outcomes

**Description:** defined as the proportion of subjects with an overall efficacy response of CR after at least one baseline evaluation during the trial;

**Measure:** Complete Remission Rate (CRR)

**Time Frame:** Second cycle Day 30 / Fourth cycle Day 60 / Sixth cycle Day 90 (each cycle is 21 days)

**Description:** defined as the proportion of subjects with an overall efficacy response of CR, PR and stable disease (SD) after at least one baseline evaluation during the trial;

**Measure:** Disease Control Rate (DCR)

**Time Frame:** Second cycle Day 30 / Fourth cycle Day 60 / Sixth cycle Day 90 (each cycle is 21 days)

**Description:** defined as the duration from first remission (PR and above) to disease progression or death;

**Measure:** Duration of remission (DOR)

**Time Frame:** Second cycle Day 30 / Fourth cycle Day 60 / Sixth cycle Day 90 (each cycle is 21 days)

**Description:** defined as the time from first dose to the appearance of PR and beyond;

**Measure:** Time to Tumor Remission (TTR)

**Time Frame:** Second cycle Day 30 / Fourth cycle Day 60 / Sixth cycle Day 90 (each cycle is 21 days)

**Description:** defined as the time from first dose to disease progression or death

**Measure:** Progression-free survival (PFS)

**Time Frame:** Second cycle Day 30 / Fourth cycle Day 60 / Sixth cycle Day 90 (each cycle is 21 days)

**Description:** defined as the time from first dose to death.

**Measure:** Overall survival (OS)

**Time Frame:** Second cycle Day 30 / Fourth cycle Day 60 / Sixth cycle Day 90 (each cycle is 21 days)

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. age: ≥18 years and ≤75 years, regardless of gender;
2. at least one measurable lesion as defined by RECIST 1.1 in the Screening Phase (non-measurable lesions with simple bone metastases only are acceptable in the Dose Escalation Phase of the Breast Cancer Cohort);
3. single-agent dose-escalation phase in Phase Ib: Locally advanced or metastatic solid tumors, including but not limited to triple-negative breast cancer, colorectal cancer, and uroepithelial carcinoma, that have been diagnosed by histologic or cytologic confirmation of pathology and have failed standard therapy, or for which there is no standard treatment regimen available or for which standard therapy is not appropriate at this stage;

Phase Ib Combination Dose Escalation Phase:

1. Combination exemestane for Cohort A (breast cancer):

   Perimenopausal, premenopausal, and postmenopausal women with breast cancer confirmed by histopathology or cytologic pathology to be estrogen receptor (ER)-positive, progesterone receptor (PgR)-negative or -positive, and non-HER2-positive (including HER2-negative and low-expressing populations); Progression or recurrence after at least 1 line of prior endocrine therapy (whether at advanced stage, in the setting of metastasis, or with neoadjuvant chemotherapy), and prior availability of no more than 1 line of chemotherapy (note: if prior endocrine therapy was adjuvant to exemestane, the disease-free interval after discontinuation of exemestane needs to be \>12 months); Not suitable for surgical resection therapy; Definition of menopause is subject to one of the following conditions: a) prior bilateral oophorectomy; b) 60 years of age and older; c) younger than 60 years of age, not on chemotherapy, tamoxifen, toremifene, or ovarian suppression therapy within one year prior to enrollment, who has been naturally menopausal for more than 12 months, and whose serum follicle-stimulating hormone and oestradiol are at postmenopausal levels; d) younger than 60 years of age, who is undergoing tamoxifen moxifene or toremifene therapy, and serum follicle-stimulating hormone and estradiol levels are in the postmenopausal range for two consecutive periods; e). Failure to meet the above criteria is considered to be in the premenopausal or perimenopausal period, and female subjects will be required to meet the following criteria: initiation of a luteinizing hormone-releasing hormone (LHRH) agonist, such as goserelin, leuprolide, etc., at least 28 ± 2 prior to the first administration of study drug (hormone level eligibility will be required for those who have been on an LHRH agonist for ≥ 21 days and \< 26 days prior to the first administration of the study drug), and the subject requires continued use of this class of medication for the duration of study treatment;
2. Combination tirilizumab for treatment of Cohort B (solid tumors):

Patients with locally advanced or metastatic solid tumors who have a cytologically or histologically confirmed diagnosis and have failed standard therapy, or for whom there is no standard therapeutic regimen, or for whom standard therapy is not appropriate at this stage, as defined by standard therapy failure for each tumor type below:

Non-small cell lung cancer: (1) patients with metastatic no driver mutation: disease progression or recurrence after at least second-line treatment (including platinum-containing chemotherapy); (2) patients whose tumors have driver mutations such as EGFR, ROS1, ALK, etc., should have received a failed targeted therapy against these mutations, and then after at least second-line treatment (including platinum-containing chemotherapy) disease progression or recurrence; Small cell lung cancer: disease progression or recurrence after at least two lines of prior therapy; Colorectal cancer: disease progression or recurrence after at least two lines of prior therapy (standard chemotherapy regimens received include fluorouracil or its derivatives, oxaliplatin, and irinotecan, BRAF inhibitors for patients with BRAF V600E mutation, and PD-1/PD-L1 therapy for those who meet the MSI-H/dMMR criteria). (treatment); Squamous cell carcinoma of the head and neck: disease progression or recurrence after at least two lines of prior therapy, including platinum-containing chemotherapy; Uroepithelial carcinoma: disease progression or recurrence after at least two lines of prior therapy (guideline-recommended regimens include PD-1/PD-L1 therapy, platinum-containing chemotherapy regimens, paclitaxel-based chemotherapy regimens, vediclizumab, and vincristine, and erdatinib has been used in patients with FGFR2/3 mutations); Esophageal cancer: disease progression or recurrence after at least two lines of prior therapy, including platinum-containing chemotherapy; cervical cancer: disease progression or recurrence after at least two lines of prior therapy (including platinum-containing chemotherapy; patients meeting the criteria for PD-L1 positivity or TMB-H or MSI-H/dMMR need to have been treated with PD-1/PD-L1) Hepatocellular carcinoma: Disease progression or recurrence after at least two lines of prior therapy; Renal cell carcinoma: disease progression or recurrence after at least two lines of prior therapy;

Phase IIa Dose Expansion Phase:

The tumor type and tumor tissue biomarker requirements for each expansion cohort enrolled in Phase IIa will be based on Phase Ib data and SMC discussion for further decision making; 4. ECOG ≤ 1 point; 5. expected survival ≥ 12 weeks; 6. organ function levels must meet the following requirements:

1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L;
2. Hemoglobin (HGB) ≥ 90 g/L;
3. Platelet count (PLT) ≥100×109/L;
4. serum creatinine ≤1.5 × ULN or estimated creatinine clearance ≥60 mL/min (according to the Cockcroft and Gault formula);
5. serum total bilirubin (TBil) ≤ 1.5 x ULN, allowing TBil \> 1.5 x ULN but direct bilirubin (DBil) \< ULN for subjects with hepatic metastases or GILBERT syndrome; and AST and ALT ≤ 2.5 x ULN, allowing AST/ALT ≤ 5 x ULN for subjects with hepatic metastases or GILBERT syndrome; 7. those who agree to participate in this study and sign the informed consent form; 8. remission of all acute toxicities from prior anticancer therapy or surgery to baseline severity or NCI-CTCAE version 5.0 ≤ Grade 1 (with the exception of alopecia or other toxicities deemed by the investigator to pose no safety risk to the patient).

Exclusion Criteria:

1. a known severe allergy to the study drug, combination drug, or any of its excipients (hydroxypropyl betacyclodextrin, arginine, glucosamine, mannitol);
2. current or prior other malignancy (except adequately treated basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the uterine cervix) unless treated radically and with evidence of recurrence-free metastasis within the last 5 years;
3. symptomatic central nervous system (CNS) metastases or asymptomatic CNS metastases requiring steroid therapy within 2 weeks prior to the first dose of study drug. Subjects with carcinomatous meningitis or molluscum contagiosum spread;
4. last systemic antineoplastic therapy (chemotherapy, targeted therapy, immunotherapy, biologic agent therapy, etc.) within 4 weeks prior to the first PM administration, with the following stipulations: nitrosoureas (e.g., carmustine, lomustine, etc.) or mitomycin C within 6 weeks prior to the first administration of the study drug; oral fluorouracil, small molecule targeted drugs within 2 weeks prior to the first administration of the study drug, or within 2 weeks prior to the first administration of a known drug within 5 half-lives (whichever is longer); local palliative radiotherapy within 2 weeks prior to the first administration of study drug; final administration of endocrine therapy within 4 weeks prior to the first administration of study drug; and receipt of herbal or proprietary Chinese medicine with an antitumor indication within 2 weeks prior to the first administration of study drug;
5. patients who have received a prior HDAC inhibitor;
6. patients with prior exemestane therapy are not eligible for enrollment in the combination exemestane treatment cohort, but are permitted to be included if the patient has a disease-free interval DFI of \>12 months after exemestane adjuvant therapy;
7. patients previously treated with anti-PD-1/PD-L1 antibodies are not eligible for enrollment in the combination tirilizumab treatment cohort, unless the patient has had a prior benefit after treatment in the advanced/metastatic phase\* then inclusion is permitted;

   * Benefit following anti-PD-1/PD-L1 antibody therapy is defined as meeting any of the following:

     1. Best efficacy of CR or PR as assessed by imaging after receiving anti-PD-1/PD-L1 antibody therapy alone or in combination with targeted/other immunologic agents;
     2. Treatment with anti-PD-1/PD-L1 antibody in combination with chemotherapy with no imaging evidence of disease progression within ≤ 6 months of treatment.
8. those who have had a serious infection within 4 weeks prior to the first administration of PM, or who have had an active infection requiring oral or intravenous antibiotic therapy within the previous 2 weeks;
9. receiving blood transfusions, recombinant human thrombopoietin, recombinant human interleukin-11, erythropoietin, and granulocyte colony-stimulating factor within 2 weeks prior to the first dose of study drug;
10. breast cancer: symptomatic, advanced patients who have disseminated to viscera and are at short-term risk of life-threatening complications (patients with visceral crises), patients with inflammatory breast cancer;
11. prior immune-related adverse events of grade ≥3 on immunotherapy are not eligible for enrollment in the combination tirilizumab treatment cohort;
12. patients with active or pre-existing autoimmune disease with potential for relapse (e.g., systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.) are not eligible for enrollment in the cohort of co-tirilizumab; the following patients are allowed: patients with type I diabetes mellitus, and patients with autoimmune thyroiditis who may be eligible for alternative therapy;
13. Patients who have received systemically administered corticosteroids (prednisone \> 10 mg/day or equivalent) or other immunosuppressive agents within 14 days prior to the first dose of PM are not eligible for enrollment in the cohort of co-tirilizumab therapy; except for the following: treatment with topical, ophthalmic, intra-articular, intranasal, and inhaled corticosteroids, and short-term prophylactic use of corticosteroids, eg. use of contrast media.
14. have uncontrolled or significant cardiovascular disease, including: (1) New York Heart Association (NYHA) Class II or greater congestive heart failure, unstable angina, myocardial infarction within 6 months prior to the first dose of PM, or the presence of an arrhythmia requiring treatment, left ventricular ejection fraction (LVEF) \<50% at screening; (2) Primary cardiomyopathy (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, undetermined cardiomyopathy); (3) Screening-phase symptomatic coronary heart disease requiring pharmacologic treatment; (4) A history of clinically significant QTcF interval prolongation or a mean corrected QT interval (QTc) \>450 msec (men) or \>470 msec (women) on 3 electrocardiograms (ECGs) of the QTcF interval during the screening period (retesting is required and 3 average corrected values are taken only if the first ECG suggests that the QTc is \>450 msec (men) or \>470 msec (women)). (only the first ECG suggesting a QTc \>450 msec (men) or \>470 msec (women) needs to be retested and averaged over 3 corrections); a history of long QT syndrome or a confirmed family history of long QT syndrome; a history of clinically significant ventricular arrhythmia or current use of antiarrhythmic medications or implantation of defibrillation devices for the treatment of ventricular arrhythmias; (5) Cerebrovascular accident (including cerebral hemorrhage, cerebral infarction, transient ischemic attack, etc.) within 6 months prior to the first dose of PM; (6) Inadequate blood pressure control during the screening period (whether or not on antihypertensive medication): systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg; (7) Other cardiovascular diseases judged by the investigator to be inappropriate for enrollment.
15. Uncontrolled electrolyte disturbances that may interfere with the action of QTc prolonging medications (e.g., hypocalcemia \<1.0 mmol/L, hypokalemia \<lower limit of normal, hypomagnesemia \<0.5 mmol/L), but retesting after interventional therapy is permitted;
16. current or past history of interstitial lung disease of any severity and/or severely impaired lung function;
17. the presence of third interstitial fluid (e.g., pleural fluid and ascites) that cannot be controlled by drainage or other means;
18. major surgical procedures requiring general anesthesia or not withdrawn from other clinical trials within 4 weeks prior to the first dose of PM; surgical procedures requiring local/epidural anesthesia from which the patient has not recovered (except for tissue biopsy) within 2 weeks prior to enrollment;
19. clinically significant active infection of the following, including hepatitis B (HBV) and hepatitis C (HCV). Active hepatitis B was defined as subjects who were HBsAg-positive or HBcAb-positive with HBV-DNA above the lower limit of detection (i.e., the upper limit of normal values in the testing department of each study center), who achieved HBV-DNA negativity after antiviral treatment, who received antiviral medications for at least 2 weeks prior to the first dose of medication, and who were willing to continue to be treated with anti-hepatitis B virus for the duration of the study were allowed to enroll in the study, and active Hepatitis C was defined as HCV antibody positivity and HCV-RNA above the lower limit of detection (upper limit of normal). Positive syphilis spirochete antibody (TP-Ab) and positive syphilis non-specific antibody titer (RPR);
20. a history of immunodeficiency, including a positive test for antibodies to human immunodeficiency virus (HIV), or other acquired, congenital immunodeficiency disease, or a history of organ transplantation;
21. participation in another interventional clinical trial within 4 weeks prior to enrollment;
22. female patients who are pregnant or breastfeeding or who are unable to ensure the use of contraception during the study period and for at least 6 months after the last treatment with poystat
23. other serious acute or chronic medical or psychiatric conditions or abnormal laboratory tests that may increase the risk of participation in the study or increase the risk associated with administration of the study drug or interfere with the results of the study, and other conditions that, in the opinion of the investigator, make the patient unsuitable for participation in this study.

**Maximum Age:** 75 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** bailing_stt@126.com

**Name:** Liangkun Sun, bachelor

**Phone:** 15885742617

**Role:** CONTACT

**Contact 2:**

**Email:** zhengjiang@zenitar.cn

**Name:** Zheng Jiang, bachelor

**Phone:** 19048075294

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Guanzhou

**Contacts:**

***Contact 1:***

- **Email:** sysyxllwyh@163.com

- **Name:** Liushan Qu

- **Phone:** 020-81332587

- **Role:** CONTACT

**Country:** China

**Facility:** Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

**State:** Guangzhou

**Zip:** 510000

**Location 2:**

**City:** Chengdu

**Country:** China

**Facility:** Chengdu Xinhua Hospital

**State:** Sichuan

**Zip:** 610000

#### Overall Officials

**Official 1:**

**Affiliation:** Sun Yat-sen Memorial Hospital,Sun Yat-sen University

**Name:** Herui Yao, Doctor

**Role:** PRINCIPAL_INVESTIGATOR

**Official 2:**

**Affiliation:** West China Hospital

**Name:** Yongsheng Wang, Doctor

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Meshes

- ID: D000009369

- Term: Neoplasms

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M137899

- Name: Tislelizumab

- Relevance: LOW

- As Found: Unknown

- ID: M247237

- Name: Exemestane

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
