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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05403450




Registration number
NCT05403450
Ethics application status
Date submitted
23/05/2022
Date registered
3/06/2022

Titles & IDs
Public title
A Study of Tolinapant in Combination With Oral Decitabine/Cedazuridine and Oral Decitabine/Cedazuridine Alone in Participants With Relapsed/Refractory Peripheral T-cell Lymphoma (R/R PTCL)
Scientific title
A Phase 1-2, Open-Label Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Activity of Tolinapant in Combination With Oral Decitabine/Cedazuridine and Oral Decitabine/Cedazuridine Alone in Subjects With Relapsed/Refractory Peripheral T-cell Lymphoma
Secondary ID [1] 0 0
2021-005338-40
Secondary ID [2] 0 0
ASTX660-03
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed/Refractory Peripheral T-cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tolinapant
Treatment: Drugs - Decitabine + Cedazuridine

Experimental: Phases 1 and 2: Tolinapant + Oral Decitabine/Cedazuridine - Tolinapant, orally, once daily (QD) on Days 1 to 7 and 15 to 21 of each 28-day cycle in combination with oral decitabine/cedazuridine fixed-dose combination (FDC) tablet, QD on days determined by the Lead-in Phase during each 28-day cycle. The starting dose of tolinapant will be escalated stepwise in successive cohorts until the RP2D is determined.

Based on RP2D and results determined from Phase 1 participants would receive tolinapant at the identified RP2D in combination with decitabine/cedazuridine, FDC tablet, orally, QD on days determined by the Lead-in Phase during each 28-day cycle in Phase 2.

Experimental: Phase 1: Oral Decitabine/Cedazuridine - Decitabine/cedazuridine FDC tablet, orally, QD on days determined by the Lead-in Phase during each 28-day cycle.


Treatment: Drugs: Tolinapant
Capsule for oral administration

Treatment: Drugs: Decitabine + Cedazuridine
Tablet for oral administration
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Dose Limiting Toxicities (DLTs)
Timepoint [1] 0 0
Up to 54 months
Primary outcome [2] 0 0
Phase 2: Antitumor Activity Assessed by Overall Response Rate (ORR) Based on 2014 Lugano Classification Using Computerized Tomography (CT) Imaging as the Primary Modality
Timepoint [2] 0 0
Up to 54 months
Secondary outcome [1] 0 0
Phase 1: Number of Participants With TEAEs, SAEs and DLTs in the Oral Decitabine/Cedazuridine Arm
Timepoint [1] 0 0
Up to 54 months
Secondary outcome [2] 0 0
Ph 1 & 2: AUC: Area Under the Plasma Concentration-Time Curve
Timepoint [2] 0 0
Up to 50 months
Secondary outcome [3] 0 0
Ph 1 & 2: Cmax: Maximum Observed Plasma Concentration
Timepoint [3] 0 0
Up to 50 months
Secondary outcome [4] 0 0
Ph 1 & 2: Cmin: Minimum Observed Plasma Concentration at Steady State
Timepoint [4] 0 0
Up to 50 months
Secondary outcome [5] 0 0
Ph 1 & 2: Tmax: Time to Maximum Observed Plasma Concentration
Timepoint [5] 0 0
Up to 50 months
Secondary outcome [6] 0 0
Ph 1 & 2: t½: Apparent Elimination Half-Life
Timepoint [6] 0 0
Up to 50 months
Secondary outcome [7] 0 0
Phase 2: Duration of response (DOR) Based on the Lugano Classification Using CT Imaging as the Primary Modality
Timepoint [7] 0 0
Up to 54 months
Secondary outcome [8] 0 0
Phase 2: Percentage of Participants With Complete Response (CR) Based on the Lugano Classification Using CT Imaging as the Primary Modality
Timepoint [8] 0 0
Up to 54 months
Secondary outcome [9] 0 0
Phase 2: Percentage of Participants With Partial Response (PR) Based on the Lugano Classification Using CT Imaging as the Primary Modality
Timepoint [9] 0 0
Up to 54 months
Secondary outcome [10] 0 0
Phase 2: Progression-Free Survival (PFS) Based on the Lugano Classification Using CT Imaging as the Primary Modality
Timepoint [10] 0 0
Up to 54 months
Secondary outcome [11] 0 0
Phase 2: Disease Control Rate (DCR) Assessed as Percentage of Participants With Disease Control Based on the Lugano Classification Using CT Imaging as the Primary Modality
Timepoint [11] 0 0
Up to 54 months
Secondary outcome [12] 0 0
Phase 2: Overall Survival (OS) Based on the Lugano Classification Using CT Imaging as the Primary Modality
Timepoint [12] 0 0
Up to 54 months
Secondary outcome [13] 0 0
Phase 2: Percentage of Participants With DOR, CR, PR, PFS, DCR,and OS Based on the Lugano Classification Using CT Along With PET Imaging Assessments
Timepoint [13] 0 0
Up to 54 months
Secondary outcome [14] 0 0
Phase 2: Percentage of Participants With Anti-Tumor Activity Based on Assessment Using 2014 Lugano Classification With Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC)
Timepoint [14] 0 0
Up to 54 months
Secondary outcome [15] 0 0
Phase 2: Percentage of Participants With Anti-Tumor Activity Based on PTCL Subtypes Anti-tumor activity in terms of ORR, DOR, DCR, CR, and PR will be evaluated based on PTCL subtypes (using both pathology and molecular markers).
Timepoint [15] 0 0
Up to 54 months

Eligibility
Key inclusion criteria
1. Participants with expected life expectancy of >12 weeks.
2. Participants must have histologically confirmed R/R PTCL (local pathology report) as defined by 2016 World Health Organization (WHO) classification. The following subtypes are eligible for the study:

1. Extranodal natural killer (NK)/T-cell lymphoma nasal type.
2. Enteropathy-associated T-cell lymphoma.
3. Monomorphic epitheliotropic intestinal T-cell lymphoma.
4. Hepatosplenic T-cell lymphoma.
5. Subcutaneous panniculitis-like T-cell lymphoma.
6. Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS).
7. Angioimmunoblastic T-cell lymphoma.
8. Follicular peripheral T-cell lymphoma.
9. Nodal peripheral T-cell with T-follicular helper (THF) phenotype.
10. Anaplastic large-cell lymphoma (ALCL).
3. Participants must have evidence of progressive disease and must have received at least two prior systemic therapies.
4. Participants must have measurable disease by contrast-enhanced diagnostic CT (at least 1 nodal lesion >1.5 centimeters (cm) or extranodal lesions >1.0 cm).
5. Participants with CD30-positive disease must have received, be ineligible for, or intolerant to brentuximab vedotin.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
7. Acceptable organ function as per protocol.
8. Women of childbearing potential (according to recommendations of the Clinical Trial Facilitation Group [CTFG]) must not be pregnant or breastfeeding and must have a negative pregnancy test at screening.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Prior treatment with tolinapant or any hypomethylating agent.
2. Hypersensitivity to tolinapant or oral decitabine/cedazuridine, excipients of the drug product, or other components of the study treatment regimen.
3. Poor medical risk because of systemic diseases (e.g., uncontrolled infections) in addition to the qualifying disease under study.
4. Life-threatening illness, significant organ system dysfunction, or other condition that, in the investigator's opinion, could compromise participant safety or the integrity of the study outcomes, or interfere with the absorption or metabolism of tolinapant.
5. A history of, or at risk for, cardiac disease, as evidenced by 1 or more of the following conditions:

1. Abnormal left ventricular ejection fraction.
2. Congestive cardiac failure of Grade =3.
3. Unstable cardiac disease.
4. History or presence of complete left bundle branch block, third-degree heart block, cardiac pacemaker, or clinically significant arrhythmia.
5. History of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy.
6. Screening 12-lead electrocardiogram (ECG) with measurable QTc interval of =470 milliseconds (msec) (according to either Fridericia's or Bazett's correction).
7. Any other condition that, in the opinion of the investigator, could put the participant at increased cardiac risk.
6. Known history of human immunodeficiency virus (HIV) infection; or seropositive results consistent with active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection.
7. Grade 3 or greater neuropathy.
8. Known significant mental illness or other conditions such as active alcohol or other substance abuse that, in the opinion of the investigator, predisposes the participant to high risk of noncompliance with the protocol treatment or assessments.
9. Prior anticancer treatments or therapies within the indicated time window before first dose of study treatment (tolinapant), as follows:

1. Cytotoxic chemotherapy or radiotherapy within 4 weeks prior.
2. Monoclonal antibodies within 4 weeks prior.
3. At least 12 weeks must have elapsed since chimeric antigen receptor T-cell (CAR-T) infusion.
4. Small molecules or biologics (investigational or approved) within the longer of 3 weeks or 5 half-lives before study treatment.
10. Monoclonal antibody treatment for rheumatologic conditions within 4 weeks of study drug initiation.
11. Concurrent second malignancy currently requiring active therapy, except breast or prostate cancer stable on or responding to endocrine therapy or superficial bladder cancer.
12. Any concurrent second malignancy that is metastatic.
13. Known central nervous system (CNS) lymphoma.
14. Participants with a history of allogeneic transplant are excluded from this study.
15. Autotransplant within 100 days of the first dose of the study drug(s).
16. Systemic corticosteroids >10 mg prednisone equivalent within 7 days of the first dose of study drug(s).
17. Anti-T-cell directed therapy:

1. Lymphotoxic agents (e.g., anti-CD52) in the past 12 months.
2. Inhibitory drugs (e.g., calcineurin inhibitors) within 4 weeks of the first dose of study drug(s).
18. Use of a concomitant medication which is a moderate or strong CYP3A4 inhibitor/inducer within 2 weeks of the start of the study.
19. Use of any vaccine within 10 days of the first dose of the study drug(s).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/06/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2026
Actual
Sample size
Target
132
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Concord Hospital - Concord
Recruitment hospital [2] 0 0
Monash Medical Center - Melbourne
Recruitment hospital [3] 0 0
Linear Clinical Research Site #834 - Nedlands
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
3168 - Melbourne
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Virginia
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
France
State/province [13] 0 0
Indre-et-Loire
Country [14] 0 0
France
State/province [14] 0 0
Seine-Maritime
Country [15] 0 0
France
State/province [15] 0 0
Bordeaux
Country [16] 0 0
France
State/province [16] 0 0
Marseille
Country [17] 0 0
France
State/province [17] 0 0
Montpellier
Country [18] 0 0
France
State/province [18] 0 0
Nice
Country [19] 0 0
France
State/province [19] 0 0
Paris
Country [20] 0 0
France
State/province [20] 0 0
Villejuif
Country [21] 0 0
Italy
State/province [21] 0 0
Emilia-Romagna
Country [22] 0 0
Italy
State/province [22] 0 0
Forli-Cesena
Country [23] 0 0
Italy
State/province [23] 0 0
Bologna
Country [24] 0 0
Italy
State/province [24] 0 0
Brescia
Country [25] 0 0
Italy
State/province [25] 0 0
Milano
Country [26] 0 0
Italy
State/province [26] 0 0
Monza
Country [27] 0 0
Poland
State/province [27] 0 0
Lodzkie
Country [28] 0 0
Poland
State/province [28] 0 0
Masovia
Country [29] 0 0
Poland
State/province [29] 0 0
Pomerania
Country [30] 0 0
Spain
State/province [30] 0 0
Andalucía
Country [31] 0 0
Spain
State/province [31] 0 0
Catalonia
Country [32] 0 0
Spain
State/province [32] 0 0
Barcelona
Country [33] 0 0
Spain
State/province [33] 0 0
Madrid
Country [34] 0 0
Spain
State/province [34] 0 0
Santander
Country [35] 0 0
United Kingdom
State/province [35] 0 0
England

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Taiho Oncology, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05403450