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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.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

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
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
Are there results?
None posted in the registry

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

Other trials in United States

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

Other trials in Spain

Australia2 sites

  • Concord Hospital

    Concord, New South Wales, 2139

  • Monash Medical Center

    Melbourne, Victoria, 3168

Other trials in Australia

France2 sites

  • Institut Bergonié Site#553

    Bordeaux, 33000

  • Institut Paoli-Calmettes

    Marseille, 13009

Other trials in France

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

Other trials in Italy

Poland1 site

  • Ośrodek Badań Klinicznych Wczesnych Faz - Uniwersyteckie Centrum Kliniczne w Gdańsku

    Gdansk, Pomeranian Voivodeship, 80-214

Other trials in Poland

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 groups in NCT05403450
Study groupRoleWhat they receive
Phases 1 and 2: Tolinapant + Oral Decitabine/CedazuridineExperimentalTolinapant, 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/CedazuridineExperimentalDecitabine/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.

  1. 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

  2. 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)

  1. Phase 1: Number of Participants With TEAEs, SAEs and DLTs in the Oral Decitabine/Cedazuridine Arm

    Measured: Up to 54 months

  2. Ph 1 & 2: AUC: Area Under the Plasma Concentration-Time Curve

    Measured: Up to 50 months

  3. Ph 1 & 2: Cmax: Maximum Observed Plasma Concentration

    Measured: Up to 50 months

  4. Ph 1 & 2: Cmin: Minimum Observed Plasma Concentration at Steady State

    Measured: Up to 50 months

  5. Ph 1 & 2: Tmax: Time to Maximum Observed Plasma Concentration

    Measured: Up to 50 months

  6. Ph 1 & 2: t½: Apparent Elimination Half-Life

    Measured: Up to 50 months

  7. Phase 2: Duration of response (DOR) Based on the Lugano Classification Using CT Imaging as the Primary Modality

    Measured: Up to 54 months

  8. 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

  9. 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

  10. Phase 2: Progression-Free Survival (PFS) Based on the Lugano Classification Using CT Imaging as the Primary Modality

    Measured: Up to 54 months

  11. 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

  12. Phase 2: Overall Survival (OS) Based on the Lugano Classification Using CT Imaging as the Primary Modality

    Measured: Up to 54 months

  13. 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

  14. 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

  15. 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.

  1. First posted3 Jun 2022
  2. Study start22 Feb 2023
  3. Primary completion16 Dec 2024
  4. 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

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)
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

Questions about this trial

What is this clinical trial studying?

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.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States, Spain, Australia, France, Italy and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: 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.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Dose Limiting Toxicities (DLTs) (time frame: Up to 54 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05403450.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2026.

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