Trial Title:
A Clinical Study of Puesta Mesylate for Injection in Patients With Solid Tumors
NCT ID:
NCT06431243
Condition:
Advanced Solid Tumor
Conditions: Official terms:
Neoplasms
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
A group Purinostat Mesylate 6mg/m2
Description:
Purinostat Mesylate 6mg/m2 + EM 25mg
Arm group label:
A group
Intervention type:
Drug
Intervention name:
A group Purinostat Mesylate 8.4mg/m2
Description:
Purinostat Mesylate 8.4mg/m2 + EM 25mg
Arm group label:
A group
Intervention type:
Drug
Intervention name:
A group Purinostat Mesylate 11.2mg/m2
Description:
Purinostat Mesylate 11.2mg/m2 + EM 25mg
Arm group label:
A group
Intervention type:
Drug
Intervention name:
A group Purinostat Mesylate 15.0mg/m2
Description:
Purinostat Mesylate 15.0mg/m2 + EM 25mg
Arm group label:
A group
Intervention type:
Drug
Intervention name:
B group Purinostat Mesylate 6.0mg/m2
Description:
Purinostat Mesylate 6.0mg/m2 + Tislelizumab 200mg
Arm group label:
B group
Intervention type:
Drug
Intervention name:
B group Purinostat Mesylate 8.4 mg/m2
Description:
Purinostat Mesylate 8.4mg/m2 + Tislelizumab 200mg
Arm group label:
B group
Intervention type:
Drug
Intervention name:
B group Purinostat Mesylate 11.2 mg/m2
Description:
Purinostat Mesylate 11.2mg/m2 + Tislelizumab 200mg
Arm group label:
B group
Intervention type:
Drug
Intervention name:
B group Purinostat Mesylate 15.0 mg/m2
Description:
Purinostat Mesylate 15.0mg/m2 + Tislelizumab 200mg
Arm group label:
B group
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.
Criteria for 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
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
Address:
City:
Guanzhou
Zip:
510000
Country:
China
Contact:
Last name:
Liushan Qu
Phone:
020-81332587
Email:
sysyxllwyh@163.com
Facility:
Name:
Chengdu Xinhua Hospital
Address:
City:
Chengdu
Zip:
610000
Country:
China
Start date:
May 31, 2024
Completion date:
November 1, 2026
Lead sponsor:
Agency:
Chengdu Zenitar Biomedical Technology Co., Ltd
Agency class:
Industry
Source:
Chengdu Zenitar Biomedical Technology Co., Ltd
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06431243
