Phase 1-2 Study of ASTX660 in Subjects With Advanced Solid Tumors and Lymphomas
NCT ID: NCT02503423
Last Updated: 2025-01-07
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE1/PHASE2
230 participants
INTERVENTIONAL
2015-07-31
2025-12-31
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Phase 1 - Part 1 (completed)
Dose-escalation stage to identify the MTD and the RP2D, defined as either the MTD or a dose below the MTD that the Data and Safety Review Committee (DSRC) agree shows adequate pharmacological evidence of target engagement and/or clinical activity. Subjects will receive ASTX660 once a day for 7 consecutive days every other week of each 28-day cycle (ie, \[7 days on/ 7 days off\] ×2; daily dosing on Days 1-7 and 15-21). The starting dose will be escalated stepwise in successive cohorts of 3 to 6 evaluable subjects each (standard 3+3 study design), until the RP2D is determined.
ASTX660
described above
Phase 1 - Part 2 (completed)
Dose-expansion stage to confirm tolerability of ASTX660 at the RP2D using the every-other-week daily dosing regimen. Up to a total of 12 subjects (including the 3 or 6 subjects treated at the RP2D in Part 1) will be treated at the RP2D.
ASTX660
described above
Phase 1 - Part 3 (optional)
The purpose of the optional Part 3 is to allow for exploration of an alternative dosing regimen of ASTX660 based on emerging safety, PK, and pharmacodynamic (PD) data from Parts 1 and 2 (using the original every-other-week dosing regimen), with agreement of the DSRC. If Part 3 is conducted, the plan is to enroll up to 18 evaluable subjects in 1 or more cohorts using a standard 3+3 study design.
ASTX660
described above
Phase 2 - Cohort 1
Treatment with ASTX660 for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) not responsive or relapsed after standard therapy.
ASTX660
described above
Phase 2 - Cohort 2
Treatment with ASTX660 for relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
ASTX660
described above
Phase 2 - Cohort 3
Treatment with ASTX660 for progressive or relapsed peripheral T-cell lymphoma (PTCL).
ASTX660
described above
Phase 2 - Cohort 4
Treatment with ASTX660 for relapsed or refractory cutaneous T-cell lymphoma (CTCL).
ASTX660
described above
Phase 2 - Cohort 5
Treatment with ASTX660 for other tumor types that are characterized by a molecular feature that may confer sensitivity to ASTX660 (eg, oncogenic activation of the NF-κB pathway or documented amplification of the gene loci encoding c-IAP1 or c-IAP2), pending confirmation in writing by the Astex medical monitor.
ASTX660
described above
Phase 2 - Cohort 6
Treatment with ASTX660 for cervical carcinoma not responsive or relapsed after standard therapy.
ASTX660
described above
Interventions
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ASTX660
described above
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Men and women 18 years of age or older.
3. Subjects with histologically or cytologically confirmed advanced solid tumors or lymphoma that is metastatic or unresectable, and for whom standard life-prolonging measures are not available. Specific tumor types that will be selected for study in Phase 2 are detailed in the protocol.
a. For Phase 2 Cohort 3, subjects must have histologically confirmed PTCL (local pathology report) as defined by 2016 World Health Organization (WHO) classification. The following subtypes are eligible for the study: adult T-cell lymphoma/leukemia, 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, angioimmunoblastic T-cell lymphoma, follicular T-cell lymphoma, nodal peripheral T-cell with T-follicular helper (THF) phenotype, and anaplastic large-cell lymphoma.
4. For Phase 2 Cohorts 3 and 4, patients must have evidence of documented progressive disease and must have received at least two prior systemic therapies.
1. Subjects with CD30-positive lymphoma must have received, be ineligible for, or intolerant to brentuximab vedotin, provided that brentuximab vedotin is locally approved and available.
2. Subjects with mycosis fungoides or Sezary syndrome must have received, be ineligible or intolerant to mogamulizumab, provided that mogamulizumab is locally approved and available.
5. In the Phase 2 portion of the protocol only, subjects must have measurable disease according to response criteria appropriate for their type of cancer.
a. For Phase 2 Cohort 3 (PTCL), measurable disease by contrast-enhanced diagnostic CT (at least 1 nodal lesion \>1.5 cm or extranodal lesions \>1.0 cm) is required.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
7. Acceptable organ function, as evidenced by the following laboratory data:
1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<=2.0 \* upper limit of normal (ULN).
2. Total serum bilirubin \<=1.5 \* ULN
3. Absolute neutrophil count (ANC):
* Phase 1 and 2 (except Phase 2 subjects with known lymphoma; ie, not applicable for Cohorts 3 or 4) \>=1500 cells/mm3
* Phase 2 subjects with known lymphoma: \>=1000 cells/mm3 (\>750 cell/mm3 for subjects with lymphoma in bone marrow)
4. Platelet count:
* Phase 1 and 2 (except Phase 2 subject with known lymphoma; ie, not applicable for Cohorts 3 or 4) \>=100,000 cells/mm3
* Phase 2 subjects with known lymphoma: \>= 50,000 cells/mm3; \>=25,000 cells/mm3 for subjects with lymphoma in bone marrow
5. Serum creatinine levels \<= 1.5 \* ULN, or calculated (by Cockcroft-Gault formula or other accepted formula) or measure creatinine clearance \>=50 mL/min.
6. Amylase and lipase \<=ULN.
8. Women of child-bearing potential (according to recommendations of the Clinical Trial Facilitation Group \[CTFG\]; see protocol for details) must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of child-bearing potential and men with female partners of child-bearing potential must agree to practice 2 highly effective contraceptive measures of birth control (as described in the protocol) and must agree not to become pregnant or father a child while receiving treatment with study drug and for at least 3 months after completing treatment. Contraceptive measures which may be considered highly effective comprise combined hormonal contraception (oral, vaginal, or transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, sexual abstinence, and surgically successful vasectomy. Abstinence is acceptable only if it is consistent with the preferred and usual lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of birth control.
Exclusion Criteria
2. Poor medical risk because of systemic diseases (e.g. active uncontrolled infections) in addition to the qualifying disease under study.
3. Life-threatening illness, significant organ system dysfunction, or other condition that, in the investigator's opinion, could compromise subject safety or the integrity of the study outcomes, or interfere with the absorption or metabolism of ASTX660.
4. History of, or at risk for, cardiac disease, as evidenced by 1 or more of the following conditions:
1. Abnormal left ventricular ejection fraction (LVEF; \<50%) or echocardiogram ECHO or multiple gated acquisition scan (MUGA).
2. Congestive cardiac failure of \>= Grade 3 severity according to New York Heart Association (NYHA) functional classification defined as subjects with marked limitation of activity and who are comfortable only at rest.
3. Unstable cardiac disease including angina or hypertension as defined by the need for overnight hospital admission within the last 3 months (90 days).
4. History or presence of complete left bundle branch block, heart block, cardiac pacemaker or significant arrhythmia.
5. Concurrent treatment with any medical that prolongs QT interval and may induce torsades de pointes, and which cannot be discontinued at least 2 weeks before treatment with ASTX660. \[Applies to Phase 1 only\].
6. Personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy.
7. Screening 12-lead ECG with measurable QTc interval (according to either Fridericia's or Bazett's correction) of \>=470 msec).
8. Any other condition that, in the opinion of the investigator, could put the subject at increased cardiac risk.
5. 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.
6. Grade 2 or greater neuropathy \[Applies to Phase 1\]. Grade 3 or greater neuropathy \[Applies to Phase 2\].
7. Known brain metastases, unless stable or previously treated.
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 subject to high risk of noncompliance with the protocol treatment or assessments.
9. Prior anticancer treatments or therapies within the indicated time window prior to first dose of study treatment (ASTX660), as follows:
1. Cytotoxic chemotherapy or radiotherapy within 3 weeks prior and any encountered treatment-related toxicities (excepting alopecia) not resolved to Grade 1 or less \[Phase 1\] or Grade 2 or less \[Phase 2\].
2. Skin directed treatments, including topicals and radiation within 2 weeks prior.
3. Monoclonal antibodies within 4 weeks prior and any encountered treatment-related toxicities not resolved to Grade 1 or less \[Phase 1\] or Grade 2 or less \[Phase 2\].
4. Small molecules or biologics (investigational or approved) within the longer of 2 weeks or 5 half-lives prior to study treatment and any encountered treatment-related toxicities not resolved to Grade 1 or less \[Phase 1\] or Grade 2 or less \[Phase 2\].
5. At least 6 weeks must have elapsed since CAR-T infusion and subjects must have experienced disease progression, and not have residual circulating CAR-T cells in peripheral blood (based on local assessment). Any encountered treatment-related toxicities must have resolved to Grade ≤1.
10. Concurrent second malignancy currently requiring active therapy, except breast or prostate cancer stable on or responding to endocrine therapy or superficial bladder cancer \[Phase 2\].
11. Known central nervous system (CNS) lymphoma \[Phase 2\].
12. Patients with a history of allogenic transplant must not have ≥Grade 3 graft-versus-host disease (GVHD) or any clinically significant GVHD requiring systemic immunosuppression \[Phase 2\].
13. Systemic corticosteroids \>20 mg prednisone equivalent (unless patient has been taking a continuous dose for \>3 weeks prior to study entry and there is documented radiological progression) \[Phase 2\]. Stable dose of medium or low potency topical corticosteroids for at least 3 weeks prior to study entry are permitted \[Phase 2\].
18 Years
ALL
No
Sponsors
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Taiho Oncology, Inc.
INDUSTRY
Responsible Party
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Locations
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University of Alabama at Birmingham
Birmingham, Alabama, United States
HonorHealth Research Institute
Scottsdale, Arizona, United States
USC/Norris Comprehensive Cancer Center
Los Angeles, California, United States
Cedars-Sinai Medical Center
Los Angeles, California, United States
UC Davis Medical Center
Sacramento, California, United States
Simlow Cancer Hospital at Yale
New Haven, Connecticut, United States
Emory University winship Cancer Institute
Atlanta, Georgia, United States
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago, Illinois, United States
The Sidney Kimmel Comprehensive Cancer Center at John Hopkins
Baltimore, Maryland, United States
Tufts Medical Center
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
University of Michigan
Ann Arbor, Michigan, United States
Dartmouth-Hitchcock Medical Center (DHMC)
Lebanon, New Hampshire, United States
Summit Medical Group - Florham Park Campus/Atlantic Health
Florham Park, New Jersey, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
New York University Langone Medical Center
New York, New York, United States
New York Presbyterian Hospital Columbia University Medical Center
New York, New York, United States
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Rochester Skin Lymphoma Medical Group
Rochester, New York, United States
Wake Forest Baptist Health
Winston-Salem, North Carolina, United States
The Ohio State University and Wexner Medical Center, James Cancer Hospital
Columbus, Ohio, United States
University of Oklahoma Stephenson Cancer Center
Oklahoma City, Oklahoma, United States
Oregon Health and Science University
Portland, Oregon, United States
West Penn Hospital
Pittsburgh, Pennsylvania, United States
Hollings Cancer Center
Charleston, South Carolina, United States
Vanderbilt Ingram Cancer Center
Nashville, Tennessee, United States
MD Anderson Cancer Center
Houston, Texas, United States
CliniCore Texas
Houston, Texas, United States
START- South Texas Accelerated Research Therapeutics
San Antonio, Texas, United States
Virgina Commonwealth University
Richmond, Virginia, United States
University of Washington, Seattle Cancer Care Alliance
Seattle, Washington, United States
Centre Hospitalier Universitaire Universite Catholique de Louvain - Site Godinne
Yvoir, Namur, Belgium
Universitair Ziekenhuis Gent
Ghent, Oost-Vlaanderen, Belgium
Intitut Jules Boredt
Brussels, , Belgium
Tom Baker Cancer Centre
Calgary, Alberta, Canada
British Columbia Cancer Agency
Vancouver, British Columbia, Canada
Cancer Care Manitoba
Winnipeg, Manitoba, Canada
Nova Scotia Health Athority-Qeii HSC
Halifax, Nova Scotia, Canada
Sunnybrook Hospital
Toronto, Ontario, Canada
Princess Margaret Cancer Centre
Toronto, Ontario, Canada
Jewish General Hospital
Montreal, Quebec, Canada
Gustave Roussy Cancer Campus (IGR)
Villejuif, Cedex, France
Centre Hospitalier Lyon Sud
Pierre-Bénite, Lyon, France
Institut Bergonié, Unicancer
Bordeaux, , France
Centre Antoine Lacassagne, Oncologie Médicale
Nice, , France
Centre Henri Becquerel, Hematology
Rouen, , France
Institut Universitaire du Cancer - Oncopôle, Department d'Hématologie
Toulouse, , France
CRU de Tours - Hôpital Bretonneau, Hématologie -Thérapy Cellulaire
Tours, , France
Semmelweis Egyetem - I. sz. Belgyógyászati Klinika
Budapest, , Hungary
Debreceni Egyetem Klinikai Központ
Debrecen, , Hungary
Szabolcs-Szatmár-Bereg Megyei Kórházak És Egyetemi Oktatókórház
Nyíregyháza, , Hungary
Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-Malpighi
Bologna, , Italy
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Brescia, , Italy
Instituto Europeo di Oncologia
Milan, , Italy
Azienda Socio Santaria Territoriale Monza- Osperdale San Gerado
Monza, , Italy
Institut Catala d'Oncologia
Girona, Giona, Spain
imCORE - Clínica Universidad de Navarra
Pamplona, Navarre, Spain
Hospital Universitario Fundacion Jimenez Diaz Preview
Madrid, , Spain
Hospital Universitario 12 de Octubre
Madrid, , Spain
University Hospitals of Leicester NHS Trust
Leicester, East Midlands, United Kingdom
University Hospital Southhampton NHS Foundation Trust - Somers Cancer Research
Southampton, Hampshire, United Kingdom
Churchill Hospital, Oxford University Hospital NHS Trust
Oxford, Oxfordshire, United Kingdom
The Royal Marsden NHS Foundation Trust
Sutton, Surrey, United Kingdom
University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
Birmingham, , United Kingdom
Beatson Cancer Center and University of Glasgow
Glasgow, , United Kingdom
University College London Hospitals NHS Foundation Trust
London, , United Kingdom
Guy's and Saint Thomas' NHS Foundation Trust
London, , United Kingdom
The Christie NHS Foundation Trust, Christie Hospital
Manchester, , United Kingdom
Countries
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References
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Johnson CN, Ahn JS, Buck IM, Chiarparin E, Day JEH, Hopkins A, Howard S, Lewis EJ, Martins V, Millemaggi A, Munck JM, Page LW, Peakman T, Reader M, Rich SJ, Saxty G, Smyth T, Thompson NT, Ward GA, Williams PA, Wilsher NE, Chessari G. A Fragment-Derived Clinical Candidate for Antagonism of X-Linked and Cellular Inhibitor of Apoptosis Proteins: 1-(6-[(4-Fluorophenyl)methyl]-5-(hydroxymethyl)-3,3-dimethyl-1 H,2 H,3 H-pyrrolo[3,2- b]pyridin-1-yl)-2-[(2 R,5 R)-5-methyl-2-([(3R)-3-methylmorpholin-4-yl]methyl)piperazin-1-yl]ethan-1-one (ASTX660). J Med Chem. 2018 Aug 23;61(16):7314-7329. doi: 10.1021/acs.jmedchem.8b00900. Epub 2018 Aug 9.
Other Identifiers
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ASTX660-01
Identifier Type: -
Identifier Source: org_study_id
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