Relapsed/Refractory Peripheral T-cell LymphomaPhase 1NCT05403450
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)
A Phase 1 study testing Tolinapant and Decitabine + Cedazuridine in people with Relapsed/Refractory Peripheral T-cell Lymphoma, run by Taiho Oncology, Inc. at 19 sites in 6 countries.
Trial summary
The primary purpose of the study is to assess safety, and to identify the recommended phase 2 dose (RP2D) of tolinapant in combination with oral decitabine/cedazuridine in Phase 1 and to assess preliminary efficacy as determined by overall response rate (ORR) in Phase 2. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed/Refractory Peripheral T-cell Lymphoma
- What is being tested?
- Tolinapant and Decitabine + Cedazuridine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 19 sitesin 6 countries
- Study dates
- 22 Feb 2023to 1 Jul 2026
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants with expected life expectancy of >12 weeks.
- 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:
- Extranodal natural killer (NK)/T-cell lymphoma nasal type.
- Enteropathy-associated T-cell lymphoma.
- Monomorphic epitheliotropic intestinal T-cell lymphoma.
- Hepatosplenic T-cell lymphoma.
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- Subcutaneous panniculitis-like T-cell lymphoma.
- Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS).
- Angioimmunoblastic T-cell lymphoma.
- Follicular peripheral T-cell lymphoma.
- Nodal peripheral T-cell with T-follicular helper (THF) phenotype.
- Anaplastic large-cell lymphoma (ALCL).
- Participants must have evidence of progressive disease and must have received at least two prior systemic therapies.
- 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).
- Participants with CD30-positive disease must have received, be ineligible for, or intolerant to brentuximab vedotin.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
- Acceptable organ function as per protocol.
- 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.
Who cannot join
- Prior treatment with tolinapant or any hypomethylating agent.
- Hypersensitivity to tolinapant or oral decitabine/cedazuridine, excipients of the drug product, or other components of the study treatment regimen.
- Poor medical risk because of systemic diseases (e.g., uncontrolled infections) in addition to the qualifying disease under study.
- 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.
- A history of, or at risk for, cardiac disease, as evidenced by 1 or more of the following conditions:
- Abnormal left ventricular ejection fraction.
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- Congestive cardiac failure of Grade ≥3.
- Unstable cardiac disease.
- History or presence of complete left bundle branch block, third-degree heart block, cardiac pacemaker, or clinically significant arrhythmia.
- History of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy.
- Screening 12-lead electrocardiogram (ECG) with measurable QTc interval of ≥470 milliseconds (msec) (according to either Fridericia's or Bazett's correction).
- Any other condition that, in the opinion of the investigator, could put the participant at increased cardiac risk.
- 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.
- Grade 3 or greater neuropathy.
- 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.
- Prior anticancer treatments or therapies within the indicated time window before first dose of study treatment (tolinapant), as follows:
- Cytotoxic chemotherapy or radiotherapy within 4 weeks prior.
- Monoclonal antibodies within 4 weeks prior.
- At least 12 weeks must have elapsed since chimeric antigen receptor T-cell (CAR-T) infusion.
- Small molecules or biologics (investigational or approved) within the longer of 3 weeks or 5 half-lives before study treatment.
- Monoclonal antibody treatment for rheumatologic conditions within 4 weeks of study drug initiation.
- Concurrent second malignancy currently requiring active therapy, except breast or prostate cancer stable on or responding to endocrine therapy or superficial bladder cancer.
- Any concurrent second malignancy that is metastatic.
- Known central nervous system (CNS) lymphoma.
- Participants with a history of allogeneic transplant are excluded from this study.
- Autotransplant within 100 days of the first dose of the study drug(s).
- Systemic corticosteroids >10 mg prednisone equivalent within 7 days of the first dose of study drug(s).
- Anti-T-cell directed therapy:
- Lymphotoxic agents (e.g., anti-CD52) in the past 12 months.
- Inhibitory drugs (e.g., calcineurin inhibitors) within 4 weeks of the first dose of study drug(s).
- Use of a concomitant medication which is a moderate or strong CYP3A4 inhibitor/inducer within 2 weeks of the start of the study.
- Use of any vaccine within 10 days of the first dose of the study drug(s).
Trial locations and contacts
19 sites in 6 countries.
19 sites in 6 countries
United States6 sites
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
University of Colorado Anschutz Medical Campus Site #118
Aurora, Colorado, 80045
The University of Texas MD Anderson Cancer Center Site #101
Houston, Texas, 77030
NYU Langone Laura and Isaac Perlmutter Cancer Center Site #153
New York, New York, 10016
University of Pennsylvania Site# 160
Philadelphia, Pennsylvania, 19104
Moffitt Cancer Center Site #157
Tampa, Florida, 33612
Spain6 sites
Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
Barcelona, Catalonia, 8908
Hospital del Mar Site #704
Barcelona, 08003
Hospital Universitario Fundación Jiménez Díaz Site #703
Madrid, 28040
Hospital Universitario 12 de Octubre Site#710
Madrid, 28041
Hospital Universitario Marqués de Valdecilla Site#711
Santander, 39008
Hospital Universitario Virgen del Rocío
Seville, Andalusia, 41013
Australia2 sites
Concord Hospital
Concord, New South Wales, 2139
Monash Medical Center
Melbourne, Victoria, 3168
France2 sites
Institut Bergonié Site#553
Bordeaux, 33000
Institut Paoli-Calmettes
Marseille, 13009
Italy2 sites
U.O.C. di Ematologia Pad. 8IRCCS Azienda OspedalieroUniversitaria di Bologna Site#651
Bologna, 40138
Fondazione IRCCS San Gerardo dei Tintori Site #655
Monza, 20900
Poland1 site
Ośrodek Badań Klinicznych Wczesnych Faz - Uniwersyteckie Centrum Kliniczne w Gdańsku
Gdansk, Pomeranian Voivodeship, 80-214
About this study
Official 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
The primary purpose of the study is to assess safety, and to identify the recommended phase 2 dose (RP2D) of tolinapant in combination with oral decitabine/cedazuridine in Phase 1 and to assess preliminary efficacy as determined by overall response rate (ORR) in Phase 2.
As no safe and tolerable dosing for the combination of tolinapant and decitabine/cedazuridine was identified based on protocol defined criteria, Sponsor decided to halt recruitment and to not conduct Phase 2 of the study.
- Being tested
- Tolinapant, Decitabine + Cedazuridine
- Keywords
- Non-Hodgkin Lymphoma
- Medical subject headings
- Lymphoma, T-Cell, Peripheral, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TolinapantDrug
Also called ASTX660
Capsule for oral administration
Decitabine + CedazuridineDrug
Also called ASTX727
Tablet for oral administration
| Study group | Role | What they receive |
|---|---|---|
| Phases 1 and 2: Tolinapant + Oral Decitabine/Cedazuridine | Experimental | 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. Receives: Drug: Tolinapant; Drug: Decitabine + Cedazuridine |
| Phase 1: Oral Decitabine/Cedazuridine | Experimental | Decitabine/cedazuridine FDC tablet, orally, QD on days determined by the Lead-in Phase during each 28-day cycle. Receives: Drug: Decitabine + Cedazuridine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Dose Limiting Toxicities (DLTs)
This will be evaluated by looking at the number of participants with treatment-related adverse events, serious adverse events (SAEs), and dose-limiting toxicities (DLTs), which are medical problems severe enough to stop study doctors from increasing a treatment dose.
Measured: Up to 54 months
Phase 2: Antitumor Activity Assessed by Overall Response Rate (ORR) Based on 2014 Lugano Classification Using Computerized Tomography (CT) Imaging as the Primary Modality
Measured: Up to 54 months
Secondary outcomes (15)
Phase 1: Number of Participants With TEAEs, SAEs and DLTs in the Oral Decitabine/Cedazuridine Arm
Measured: Up to 54 months
Ph 1 & 2: AUC: Area Under the Plasma Concentration-Time Curve
Measured: Up to 50 months
Ph 1 & 2: Cmax: Maximum Observed Plasma Concentration
Measured: Up to 50 months
Ph 1 & 2: Cmin: Minimum Observed Plasma Concentration at Steady State
Measured: Up to 50 months
Ph 1 & 2: Tmax: Time to Maximum Observed Plasma Concentration
Measured: Up to 50 months
Ph 1 & 2: t½: Apparent Elimination Half-Life
Measured: Up to 50 months
Phase 2: Duration of response (DOR) Based on the Lugano Classification Using CT Imaging as the Primary Modality
Measured: Up to 54 months
Phase 2: Percentage of Participants With Complete Response (CR) Based on the Lugano Classification Using CT Imaging as the Primary Modality
Measured: Up to 54 months
Phase 2: Percentage of Participants With Partial Response (PR) Based on the Lugano Classification Using CT Imaging as the Primary Modality
Measured: Up to 54 months
Phase 2: Progression-Free Survival (PFS) Based on the Lugano Classification Using CT Imaging as the Primary Modality
Measured: Up to 54 months
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
Measured: Up to 54 months
Phase 2: Overall Survival (OS) Based on the Lugano Classification Using CT Imaging as the Primary Modality
Measured: Up to 54 months
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
Duration of response (DOR), complete response (CR), partial response (PR), progression-free survival (PFS), disease control rate (DCR)and overall survival (OS)
Measured: Up to 54 months
Phase 2: Percentage of Participants With Anti-Tumor Activity Based on Assessment Using 2014 Lugano Classification With Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC)
Anti-tumor activity in terms of ORR, DOR, CR, PR, and PFS will be evaluated based on assessment using 2014 Lugano Classification with LYRIC.
Measured: Up to 54 months
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).
Measured: Up to 54 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2022
- Study start22 Feb 2023
- Primary completion16 Dec 2024
- Study completion1 Jul 2026
Why it stopped: ASTX660-03 was closed according to protocol as no safe and tolerable dosing for the combination of tolinapant and decitabine/cedazuridine was identified based on protocol defined criteria.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed/Refractory Peripheral T-cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Taiho Oncology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05403450
- Sponsor's protocol ID
- ASTX660-03
- Other IDs
- 2022-500391-62-00
- Status last verified
- Oct 2026
- First submitted
- 23 May 2022
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No