Clinical trial NCT05403450: 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)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Relapsed/Refractory Peripheral T-cell Lymphoma
Keywords: Non-Hodgkin Lymphoma
Lead sponsor: Taiho Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2022-06-03
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

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).

Primary outcomes:
measure: Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Dose Limiting Toxicities (DLTs)
timeFrame: Up to 54 months
measure: Phase 2: Antitumor Activity Assessed by Overall Response Rate (ORR) Based on 2014 Lugano Classification Using Computerized Tomography (CT) Imaging as the Primary Modality
timeFrame: Up to 54 months
Secondary outcomes:
measure: Phase 1: Number of Participants With TEAEs, SAEs and DLTs in the Oral Decitabine/Cedazuridine Arm
timeFrame: Up to 54 months
measure: Ph 1 & 2: AUC: Area Under the Plasma Concentration-Time Curve
timeFrame: Up to 50 months
measure: Ph 1 & 2: Cmax: Maximum Observed Plasma Concentration
timeFrame: Up to 50 months
measure: Ph 1 & 2: Cmin: Minimum Observed Plasma Concentration at Steady State
timeFrame: Up to 50 months
measure: Ph 1 & 2: Tmax: Time to Maximum Observed Plasma Concentration
timeFrame: Up to 50 months
measure: Ph 1 & 2: t½: Apparent Elimination Half-Life
timeFrame: Up to 50 months
measure: Phase 2: Duration of response (DOR) Based on the Lugano Classification Using CT Imaging as the Primary Modality
timeFrame: Up to 54 months
measure: Phase 2: Percentage of Participants With Complete Response (CR) Based on the Lugano Classification Using CT Imaging as the Primary Modality
timeFrame: Up to 54 months
measure: Phase 2: Percentage of Participants With Partial Response (PR) Based on the Lugano Classification Using CT Imaging as the Primary Modality
timeFrame: Up to 54 months
measure: Phase 2: Progression-Free Survival (PFS) Based on the Lugano Classification Using CT Imaging as the Primary Modality
timeFrame: Up to 54 months
measure: 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
timeFrame: Up to 54 months
measure: Phase 2: Overall Survival (OS) Based on the Lugano Classification Using CT Imaging as the Primary Modality
timeFrame: Up to 54 months
measure: 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
timeFrame: Up to 54 months
measure: Phase 2: Percentage of Participants With Anti-Tumor Activity Based on Assessment Using 2014 Lugano Classification With Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC)
timeFrame: Up to 54 months
measure: 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).
timeFrame: Up to 54 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Site #151
state: California
city: Los Angeles
country: United States
facility: University of Califonia, Los Angeles
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus Site #118
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center Site #109
state: Connecticut
city: Tampa
country: United States
facility: Moffitt Cancer Center Site #157
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Rogel Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute Site#159
state: Michigan
city: Fairport
country: United States
facility: Rochester Skin Lymphoma Medical Group, PLLC Site #147
state: New York
city: New York
country: United States
facility: NYU Langone Laura and Isaac Perlmutter Cancer Center Site #153
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania Site# 160
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center Site #101
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Comprehensive Cancer Center
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Concord
country: Australia
facility: Concord Hospital
state: New South Wales
city: Melbourne
country: Australia
facility: Monash Medical Center
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research Site #834
city: Tours
country: France
facility: Hôpital Bretonneau
state: Indre-et-Loire
city: Rouen
country: France
facility: Centre Henri Becquerel
state: Seine-Maritime
city: Bordeaux
country: France
facility: Institut Bergonié Site#553
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Montpellier
country: France
facility: CHU Saint-Eloi Site#556
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: AP-HP Pitie Saltpetriere Site# 552
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Ravenna
country: Italy
facility: Ospedale Santa Maria delle Croci di Ravenna
state: Emilia-Romagna
city: Meldola
country: Italy
facility: Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST
state: Forli-Cesena
city: Bologna
country: Italy
facility: U.O.C. di Ematologia Pad. 8IRCCS Azienda OspedalieroUniversitaria di Bologna Site#651
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale (ASST) degli Spedali Civili di Brescia Site#650
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia Site#652
city: Monza
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori Site #655
city: Lodz
country: Poland
facility: Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Łodzi
state: Lodzkie
city: Warsaw
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
state: Masovia
city: Gdańsk
country: Poland
facility: Ośrodek Badań Klinicznych Wczesnych Faz - Uniwersyteckie Centrum Kliniczne w Gdańsku
state: Pomerania
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
state: Andalucía
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
state: Catalonia
city: Barcelona
country: Spain
facility: Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
state: Catalonia
city: Barcelona
country: Spain
facility: Hospital del Mar Site #704
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz Site #703
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre Site#710
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla Site#711
city: London
country: United Kingdom
facility: Guy's and Saint Thomas' NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
state: England
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: England
Study officials:
References: