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)

NCT05403450 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: ASTX660-032021-005338-40
• Study Type: interventional
• Target: 33
• Locations: 7 countries
• Sites: 46

Brief 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. 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.

Conditions

Relapsed/Refractory Peripheral T-cell Lymphoma

Keywords

Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• 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.

  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

  Up to 54 months

Secondary Outcomes (15)

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

  Up to 54 months

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

  Up to 50 months

• Ph 1 & 2: Cmax: Maximum Observed Plasma Concentration

  Up to 50 months

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

  Up to 50 months

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

  Up to 50 months

Study Arms (2)

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.

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.

Drug: Decitabine + Cedazuridine

Interventions

Tolinapant DRUG

Capsule for oral administration

Also known as: ASTX660

Phases 1 and 2: Tolinapant + Oral Decitabine/Cedazuridine

Decitabine + Cedazuridine DRUG

Tablet for oral administration

Also known as: ASTX727

Phase 1: Oral Decitabine/Cedazuridine; Phases 1 and 2: Tolinapant + Oral Decitabine/Cedazuridine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Taiho Oncology, Inc.: lead

Study Sites (46)

City of Hope Site #151

Duarte, California, 91010, United States

Location

University of Califonia, Los Angeles

Los Angeles, California, 90095, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

University of Colorado Anschutz Medical Campus Site #118

Aurora, Colorado, 80045, United States

Location

Yale Cancer Center Site #109

New Haven, Connecticut, 06511, United States

Location

Moffitt Cancer Center Site #157

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Barbara Ann Karmanos Cancer Institute Site#159

Detroit, Michigan, 48201, United States

Location

Rochester Skin Lymphoma Medical Group, PLLC Site #147

Fairport, New York, 14450, United States

Location

NYU Langone Laura and Isaac Perlmutter Cancer Center Site #153

New York, New York, 10016, United States

Location

University of Pennsylvania Site# 160

Philadelphia, Pennsylvania, 19104, United States

Location

The University of Texas MD Anderson Cancer Center Site #101

Houston, Texas, 77030, United States

Location

University of Virginia Comprehensive Cancer Center

Charlottesville, Virginia, 22908, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

Concord Hospital

Concord, New South Wales, 2139, Australia

Location

Monash Medical Center

Melbourne, Victoria, 3168, Australia

Location

Linear Clinical Research Site #834

Nedlands, 6009, Australia

Location

Hôpital Bretonneau

Tours, Indre-et-Loire, 37000, France

Location

Centre Henri Becquerel

Rouen, Seine-Maritime, 76038, France

Location

Institut Bergonié Site#553

Bordeaux, 33000, France

Location

Institut Paoli-Calmettes

Marseille, 13009, France

Location

CHU Saint-Eloi Site#556

Montpellier, 34295, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

AP-HP Pitie Saltpetriere Site# 552

Paris, 75013, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Ospedale Santa Maria delle Croci di Ravenna

Ravenna, Emilia-Romagna, 48121, Italy

Location

Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST

Meldola, Forli-Cesena, 47014, Italy

Location

U.O.C. di Ematologia Pad. 8IRCCS Azienda OspedalieroUniversitaria di Bologna Site#651

Bologna, 40138, Italy

Location

Azienda Socio Sanitaria Territoriale (ASST) degli Spedali Civili di Brescia Site#650

Brescia, 25123, Italy

Location

Istituto Europeo di Oncologia Site#652

Milan, 20141, Italy

Location

Fondazione IRCCS San Gerardo dei Tintori Site #655

Monza, 20900, Italy

Location

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy

Warsaw, Masovia, 02-781, Poland

Location

Ośrodek Badań Klinicznych Wczesnych Faz - Uniwersyteckie Centrum Kliniczne w Gdańsku

Gdansk, Pomeranian Voivodeship, 80-214, Poland

Location

Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Łodzi

Lodz, Łódź Voivodeship, 93-513, Poland

Location

Hospital Universitario Virgen del Rocío

Seville, Andalusia, 41013, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Catalonia, 8025, Spain

Location

Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)

Barcelona, Catalonia, 8908, Spain

Location

Hospital del Mar Site #704

Barcelona, 08003, Spain

Location

Hospital Universitario Fundación Jiménez Díaz Site #703

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre Site#710

Madrid, 28041, Spain

Location

Hospital Universitario Marqués de Valdecilla Site#711

Santander, 39008, Spain

Location

Guy's and Saint Thomas' NHS Foundation Trust

London, England, SE1 9Rt, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, England, W1T 7HA, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, England, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma, T-Cell, Peripheral; Lymphoma, Non-Hodgkin

Interventions

ASTX-660; decitabine and cedazuridine drug combination

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2022
• First Posted: June 3, 2022
• Study Start: February 22, 2023
• Primary Completion: December 16, 2024
• Study Completion: March 31, 2026
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

PL (3); GB (3); US (16); IT (6); ES (7); AU (3); FR (8)