Solid TumorsPhase 1/2NCT02503423
Phase 1-2 Study of ASTX660 in Subjects With Advanced Solid Tumors and Lymphomas
A Phase 1/2 study testing ASTX660 in people with Solid Tumors and Lymphoma, run by Taiho Oncology, Inc. at 68 sites in 8 countries.
Trial summary
This is an open-label, dose-escalation Phase 1/2 study to assess the safety of ASTX660, determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), and recommended dosing regimen, and to obtain preliminary efficacy, pharmacokinetic (PK), and target engagement data, in subjects with advanced solid… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors, Lymphoma
- What is being tested?
- ASTX660
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 253 participants
- Where
- 68 sitesin 8 countries
- Study dates
- 14 Jul 2015to Dec 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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
- Able to understand and comply with the protocol and study procedures, understand the risks involved in the study, and provide written informed consent before any study-specific procedure is performed.
- Men and women 18 years of age or older.
- Participants 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.
- For Phase 2 Cohort 3, participants 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.
- For Phase 2 Cohorts 3 and 4, participants must have evidence of documented progressive disease and must have received at least two prior systemic therapies.
- Participants with CD30-positive lymphoma must have received, be ineligible for, or intolerant to brentuximab vedotin, provided that brentuximab vedotin is locally approved and available.
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- Participants with mycosis fungoides or Sezary syndrome must have received, be ineligible or intolerant to mogamulizumab, provided that mogamulizumab is locally approved and available.
- In the Phase 2 portion of the protocol only, participants must have measurable disease according to response criteria appropriate for their type of cancer.
- 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.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
- Acceptable organ function, as evidenced by the following laboratory data:
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=2.0 * upper limit of normal (ULN).
- Total serum bilirubin <=1.5 * ULN
- Absolute neutrophil count (ANC):
- Phase 1 and 2 (except Phase 2 participants with known lymphoma; ie, not applicable for Cohorts 3 or 4) >=1500 cells/mm3
- Phase 2 participants with known lymphoma: >=1000 cells/mm3 (>750 cell/mm3 for participants with lymphoma in bone marrow)
- Platelet count:
- Phase 1 and 2 (except Phase 2 participant with known lymphoma; ie, not applicable for Cohorts 3 or 4) >=100,000 cells/mm3
- Phase 2 participants with known lymphoma: >= 50,000 cells/mm3; >=25,000 cells/mm3 for participants with lymphoma in bone marrow
- Serum creatinine levels <= 1.5 * ULN, or calculated (by Cockcroft-Gault formula or other accepted formula) or measure creatinine clearance >=50 mL/min.
- Amylase and lipase <=ULN.
- 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 participant. Periodic abstinence (eg, calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of birth control.
Who cannot join
- Hypersensitivity to ASTX660, excipients of the drug product, or other components of the study treatment regimen.
- Poor medical risk because of systemic diseases (e.g. active 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 ASTX660.
- History of, or at risk for, cardiac disease, as evidenced by 1 or more of the following conditions:
- Abnormal left ventricular ejection fraction (LVEF; <50%) or echocardiogram ECHO or multiple gated acquisition scan (MUGA).
- Congestive cardiac failure of >= Grade 3 severity according to New York Heart Association (NYHA) functional classification defined as participants with marked limitation of activity and who are comfortable only at rest.
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- Unstable cardiac disease including angina or hypertension as defined by the need for overnight hospital admission within the last 3 months (90 days).
- History or presence of complete left bundle branch block, heart block, cardiac pacemaker or significant arrhythmia.
- 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].
- Personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy.
- Screening 12-lead ECG with measurable QTc interval (according to either Fridericia's or Bazett's correction) of >=470 msec).
- 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 2 or greater neuropathy [Applies to Phase 1]. Grade 3 or greater neuropathy [Applies to Phase 2].
- Known brain metastases, unless stable or previously treated.
- 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 prior to first dose of study treatment (ASTX660), as follows:
- 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].
- Skin directed treatments, including topicals and radiation within 2 weeks prior.
- 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].
- 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].
- At least 6 weeks must have elapsed since CAR-T infusion and participants 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.
- 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].
- Known central nervous system (CNS) lymphoma [Phase 2].
- Participants 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].
- Systemic corticosteroids >20 mg prednisone equivalent (unless participant 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].
Trial locations and contacts
68 sites in 8 countries.
68 sites in 8 countries
United States31 sites
University of Michigan
Ann Arbor, Michigan, 48109
Emory University winship Cancer Institute
Atlanta, Georgia, 30322
The Sidney Kimmel Comprehensive Cancer Center at John Hopkins
Baltimore, Maryland, 21287
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Tufts Medical Center
Boston, Massachusetts, 02111
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Roswell Park Cancer Institute
Buffalo, New York, 14263
Hollings Cancer Center
Charleston, South Carolina, 29425
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago, Illinois, 60611
The Ohio State University and Wexner Medical Center, James Cancer Hospital
Columbus, Ohio, 43210
Summit Medical Group - Florham Park Campus/Atlantic Health
Florham Park, New Jersey, 07932
MD Anderson Cancer Center
Houston, Texas, 77030
CliniCore Texas
Houston, Texas, 77079
Dartmouth-Hitchcock Medical Center (DHMC)
Lebanon, New Hampshire, 03766
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Vanderbilt Ingram Cancer Center
Nashville, Tennessee, 37212
Simlow Cancer Hospital at Yale
New Haven, Connecticut, 06510
New York University Langone Medical Center
New York, New York, 10016
New York Presbyterian Hospital Columbia University Medical Center
New York, New York, 10019
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
University of Oklahoma Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
West Penn Hospital
Pittsburgh, Pennsylvania, 15224
Oregon Health and Science University
Portland, Oregon, 97239
Virgina Commonwealth University
Richmond, Virginia, 23298
Rochester Skin Lymphoma Medical Group
Rochester, New York, 14450
UC Davis Medical Center
Sacramento, California, 95817
START- South Texas Accelerated Research Therapeutics
San Antonio, Texas, 78229
HonorHealth Research Institute
Scottsdale, Arizona, 852558
University of Washington, Seattle Cancer Care Alliance
Seattle, Washington, 98109
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27157
United Kingdom9 sites
University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
Birmingham, B15 2TH
Beatson Cancer Center and University of Glasgow
Glasgow, G12 0XL
University Hospitals of Leicester NHS Trust
Leicester, East Midlands, LE1 5WW
University College London Hospitals NHS Foundation Trust
London, NW1 2PG
Guy's and Saint Thomas' NHS Foundation Trust
London, SE1 9RT
The Christie NHS Foundation Trust, Christie Hospital
Manchester, M20 4BX
Churchill Hospital, Oxford University Hospital NHS Trust
Oxford, Oxfordshire, OX3 7LE
University Hospital Southhampton NHS Foundation Trust - Somers Cancer Research
Southampton, Hampshire, SO16 6YD
The Royal Marsden NHS Foundation Trust
Sutton, Surrey, SM2 5PT
Canada7 sites
Tom Baker Cancer Centre
Calgary, Alberta
Nova Scotia Health Athority-Qeii HSC
Halifax, Nova Scotia, B3H 2Y9
Jewish General Hospital
Montreal, Quebec, H3T 1E2
Sunnybrook Hospital
Toronto, Ontario, M4N 3M5
Princess Margaret Cancer Centre
Toronto, Ontario, M56 2M9
British Columbia Cancer Agency
Vancouver, British Columbia, V5Z 4E6
Cancer Care Manitoba
Winnipeg, Manitoba, R3E 0V9
France7 sites
Institut Bergonié, Unicancer
Bordeaux, 33000
Centre Antoine Lacassagne, Oncologie Médicale
Nice, 06189
Centre Hospitalier Lyon Sud
Pierre-Bénite, Lyon, 69310
Centre Henri Becquerel, Hematology
Rouen, 1,76-38
Institut Universitaire du Cancer - Oncopôle, Department d'Hématologie
Toulouse, 31059
CRU de Tours - Hôpital Bretonneau, Hématologie -Thérapy Cellulaire
Tours, 37044
Gustave Roussy Cancer Campus (IGR)
Villejuif, Cedex, 94805
Italy4 sites
Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-Malpighi
Bologna, 40138
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Brescia, 25123
Instituto Europeo di Oncologia
Milan
Azienda Socio Santaria Territoriale Monza- Osperdale San Gerado
Monza
Spain4 sites
Institut Catala d'Oncologia
Girona, Giona
Hospital Universitario Fundacion Jimenez Diaz Preview
Madrid, 28040
Hospital Universitario 12 de Octubre
Madrid, 28041
imCORE - Clínica Universidad de Navarra
Pamplona, Navarre, 31008
Belgium3 sites
Intitut Jules Boredt
Brussels, 1000
Universitair Ziekenhuis Gent
Ghent, Oost-Vlaanderen, 9000
Centre Hospitalier Universitaire Universite Catholique de Louvain - Site Godinne
Yvoir, Namur, B-5530
Hungary3 sites
Semmelweis Egyetem - I. sz. Belgyógyászati Klinika
Budapest, 1083
Debreceni Egyetem Klinikai Központ
Debrecen, 4032
Szabolcs-Szatmár-Bereg Megyei Kórházak És Egyetemi Oktatókórház
Nyíregyháza
About this study
Official title: Phase 1-2 Study of the Safety, Pharmacokinetics, and Preliminary Activity of ASTX660 in Subjects With Advanced Solid Tumors and Lymphomas
This is an open-label, dose-escalation Phase 1/2 study to assess the safety of ASTX660, determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), and recommended dosing regimen, and to obtain preliminary efficacy, pharmacokinetic (PK), and target engagement data, in subjects with advanced solid tumors or lymphoma for whom standard life-prolonging measures are not available.
Read the detailed description
ASTX660 is a synthetic small molecule dual antagonist of cellular inhibitor of apoptosis protein (cIAP) 1 and X-linked inhibitor of apoptosis protein (XIAP) that has been shown to have potent proapoptotic and tumor growth inhibitory activity in nonclinical models. The Phase 1 portion of the study (completed) will determine the MTD, RP2D, and recommended dosing regimen. The Phase 2 portion will evaluate activity in selected tumor types. Subjects will continue to receive their assigned treatment throughout the study until the occurrence of disease progression, death, or unacceptable treatment-related toxicity, or until the study is closed by the sponsor.
- Conditions
- Solid Tumors, Lymphoma
- Being tested
- ASTX660
- Keywords
- cervical cancer, HNSCC, CTCL, PTCL, DLBCL
- Medical subject headings
- Lymphoma, Uterine Cervical Neoplasms, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ASTX660Drug
Also called Treatment of ASTX660 for advanced solid tumors and lymphomas
described above
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 - Part 1 (completed) | Experimental | 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. Receives: Drug: ASTX660 |
| Phase 1 - Part 2 (completed) | Experimental | 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. Receives: Drug: ASTX660 |
| Phase 1 - Part 3 (optional) | Experimental | 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. Receives: Drug: ASTX660 |
| Phase 2 - Cohort 1 | Experimental | Treatment with ASTX660 for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) not responsive or relapsed after standard therapy. Receives: Drug: ASTX660 |
| Phase 2 - Cohort 2 | Experimental | Treatment with ASTX660 for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Receives: Drug: ASTX660 |
| Phase 2 - Cohort 3 | Experimental | Treatment with ASTX660 for progressive or relapsed peripheral T-cell lymphoma (PTCL). Receives: Drug: ASTX660 |
| Phase 2 - Cohort 4 | Experimental | Treatment with ASTX660 for relapsed or refractory cutaneous T-cell lymphoma (CTCL). Receives: Drug: ASTX660 |
| Phase 2 - Cohort 5 | Experimental | 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. Receives: Drug: ASTX660 |
| Phase 2 - Cohort 6 | Experimental | Treatment with ASTX660 for cervical carcinoma not responsive or relapsed after standard therapy. Receives: Drug: ASTX660 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety (Phase 1) - number of subjects with AEs, DLTs, abnormal clinical laboratory values or physical exam results
Incidence of dose-limiting toxicities (DLTs) and other adverse events (AEs)
Measured: Up to 78 months
Efficacy (Phase 2) - antitumor activity assessed by objective response rate (ORR)
Antitumor activity by objective response rate
Measured: Up to 84 months
Efficacy (Phase 2) - antitumor activity assessed by disease control rate (DCR)
Antitumor activity by disease control rate
Measured: Up to 84 months
Secondary outcomes (11)
Pharmacokinetic outcome of concentration-time curve (AUC)
Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC).
Measured: First 9 weeks of study treatment
Pharmacokinetic outcome of maximum concentration (Cmax)
Assessment of pharmacokinetic parameter maximum concentration (Cmax).
Measured: First 9 weeks of study treatment
Pharmacokinetic outcome of minimum concentration (Cmin)
Assessment of pharmacokinetic parameter minimum concentration (Cmin).
Measured: First 9 weeks of study treatment
Pharmacokinetic outcome of time to maximum concentration (Tmax)
Assessment of pharmacokinetic parameter time to maximum concentration (Tmax)
Measured: First 9 weeks of study treatment
Pharmacokinetic outcome of samples over time
Assessment of pharmacokinetic parameter elimination half life (t½).
Measured: First 9 weeks of study treatment
Pharmacokinetic outcome of samples over time
Assessment of pharmacokinetic parameter of other secondary PK parameters of ASTX660 if data permit.
Measured: First 9 weeks of study treatment
Pharmacokinetic outcome of analysis of ASTX660 metabolites if applicable
Assessment of pharmacokinetic parameter analysis of ASTX660 metabolites if applicable.
Measured: First 9 weeks of study treatment
Duration of antitumor response
Time from the date of the earliest assessment of complete response or partial response to the date of relapse or death, whichever occurs earlier, or the last efficacy assessment date for subjects without a relapse or death.
Measured: Up to 84 months
Progression-free survival
Number of days from the start of the study treatment to disease progression or death, whichever occurs first.
Measured: Up to 84 months
Overall survival
Number of days from the day the subject received the first study treatment to the date of death, regardless of cause.
Measured: Up to 84 months
Assessment of target (cIAP1) engagement
Percentage degradation of cIAP1 protein in PBMCs from baseline, in response to ASTX660 treatment.
Measured: Up to 84 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2015 (estimated)
- Study start14 Jul 2015
- Primary completionOct 2022
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- More trials run by Taiho Oncology, Inc.The sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 253 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
- NCT02503423
- Sponsor's protocol ID
- ASTX660-01
- Other IDs
- 2016-005039-34, HC6-24-c206781, 2016
- Status last verified
- Mar 2026
- First submitted
- 2 Jul 2015
- Last updated
- 20 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 30091600
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1-2 Study of the Safety, Pharmacokinetics, and Preliminary Activity of ASTX660 in Subjects With Advanced Solid Tumors and Lymphomas
- ClinicalTrials.gov ID
- NCT02503423
- Acronym / sponsor ID
- ASTX660-01
- Conditions
- Solid Tumors, Lymphoma
- Keywords
- cervical cancer, HNSCC, CTCL, PTCL, DLBCL
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 253 participants (actual)
- Lead sponsor
- Taiho Oncology, Inc.Industry (pharma, biotech, devices)
- Study start
- 14 Jul 2015 (actual)
- Primary completion
- Oct 2022 (actual)
- Study completion
- Dec 2027 (estimated)
- First posted
- 21 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, dose-escalation Phase 1/2 study to assess the safety of ASTX660, determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), and recommended dosing regimen, and to obtain preliminary efficacy, pharmacokinetic (PK), and target engagement data, in subjects with advanced solid tumors or lymphoma for whom standard life-prolonging measures are not available.
Detailed description
ASTX660 is a synthetic small molecule dual antagonist of cellular inhibitor of apoptosis protein (cIAP) 1 and X-linked inhibitor of apoptosis protein (XIAP) that has been shown to have potent proapoptotic and tumor growth inhibitory activity in nonclinical models. The Phase 1 portion of the study (completed) will determine the MTD, RP2D, and recommended dosing regimen. The Phase 2 portion will evaluate activity in selected tumor types. Subjects will continue to receive their assigned treatment throughout the study until the occurrence of disease progression, death, or unacceptable treatment-related toxicity, or until the study is closed by the sponsor.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Phase 1 - Part 1 (completed) | Experimental | Drug: ASTX660Dose-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. |
| Phase 1 - Part 2 (completed) | Experimental | Drug: ASTX660Dose-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. |
| Phase 1 - Part 3 (optional) | Experimental | Drug: ASTX660The 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. |
| Phase 2 - Cohort 1 | Experimental | Drug: ASTX660Treatment with ASTX660 for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) not responsive or relapsed after standard therapy. |
| Phase 2 - Cohort 2 | Experimental | Drug: ASTX660Treatment with ASTX660 for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). |
| Phase 2 - Cohort 3 | Experimental | Drug: ASTX660Treatment with ASTX660 for progressive or relapsed peripheral T-cell lymphoma (PTCL). |
| Phase 2 - Cohort 4 | Experimental | Drug: ASTX660Treatment with ASTX660 for relapsed or refractory cutaneous T-cell lymphoma (CTCL). |
| Phase 2 - Cohort 5 | Experimental | Drug: ASTX660Treatment 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. |
| Phase 2 - Cohort 6 | Experimental | Drug: ASTX660Treatment with ASTX660 for cervical carcinoma not responsive or relapsed after standard therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Able to understand and comply with the protocol and study procedures, understand the risks involved in the study, and provide written informed consent before any study-specific procedure is performed.
- Men and women 18 years of age or older.
- Participants 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.
- For Phase 2 Cohorts 3 and 4, participants must have evidence of documented progressive disease and must have received at least two prior systemic therapies.
- In the Phase 2 portion of the protocol only, participants must have measurable disease according to response criteria appropriate for their type of cancer.
Key exclusion criteria (26 listed)
- Hypersensitivity to ASTX660, excipients of the drug product, or other components of the study treatment regimen.
- Poor medical risk because of systemic diseases (e.g. active 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 ASTX660.
- History of, or at risk for, cardiac disease, as evidenced by 1 or more of the following conditions:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ASTX660Also: Treatment of ASTX660 for advanced solid tumors and lymphomasdescribed above | Drug | Phase 1 - Part 1 (completed), Phase 1 - Part 2 (completed), Phase 1 - Part 3 (optional), Phase 2 - Cohort 1, Phase 2 - Cohort 2, Phase 2 - Cohort 3, Phase 2 - Cohort 4, Phase 2 - Cohort 5, Phase 2 - Cohort 6 |
Primary outcome
Safety (Phase 1) - number of subjects with AEs, DLTs, abnormal clinical laboratory values or physical exam results
Time frame: Up to 78 months
Incidence of dose-limiting toxicities (DLTs) and other adverse events (AEs)
Efficacy (Phase 2) - antitumor activity assessed by objective response rate (ORR)
Time frame: Up to 84 months
Antitumor activity by objective response rate
Efficacy (Phase 2) - antitumor activity assessed by disease control rate (DCR)
Time frame: Up to 84 months
Antitumor activity by disease control rate
11 secondary outcomes
Pharmacokinetic outcome of concentration-time curve (AUC)
Time frame: First 9 weeks of study treatment
Pharmacokinetic outcome of maximum concentration (Cmax)
Time frame: First 9 weeks of study treatment
Pharmacokinetic outcome of minimum concentration (Cmin)
Time frame: First 9 weeks of study treatment
Pharmacokinetic outcome of time to maximum concentration (Tmax)
Time frame: First 9 weeks of study treatment
Pharmacokinetic outcome of samples over time
Time frame: First 9 weeks of study treatment
Pharmacokinetic outcome of samples over time
Time frame: First 9 weeks of study treatment
Pharmacokinetic outcome of analysis of ASTX660 metabolites if applicable
Time frame: First 9 weeks of study treatment
Duration of antitumor response
Time frame: Up to 84 months
Progression-free survival
Time frame: Up to 84 months
Overall survival
Time frame: Up to 84 months
Assessment of target (cIAP1) engagement
Time frame: Up to 84 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2026.
- Derived from this study: PubMed 30091600Johnson 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
68 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ASTX660 in people with Solid Tumors and Lymphoma, run by Taiho Oncology, Inc. at 68 sites in 8 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 22 inclusion and 26 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: under way, not looking for participants, as of the sponsor's last update on 20 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 68 sites in United States, United Kingdom, Canada, France, Italy and 3 more countries. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Safety (Phase 1) - number of subjects with AEs, DLTs, abnormal clinical laboratory values or physical exam results (time frame: Up to 78 months). The study lists 3 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 NCT02503423, which also lists 1 linked publication.
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 20 Mar 2026.