AzTrials
AzTrials

Anatomic Stage III Breast Cancer AJCC v8Phase 1NCT06590558

Testing the Addition of an Investigational Anti-Cancer Drug, ASTX660 (Tolinapant), to a Usual Chemotherapy Treatment (Eribulin) for Treatment of Advanced Triple Negative Breast Cancer

A Phase 1 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Anatomic Stage III Breast Cancer AJCC v8 and Anatomic Stage IV Breast Cancer AJCC v8, run by National Cancer Institute (NCI).

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

This phase I/Ib trial tests the safety, side effects, best dose, and effectiveness of ASTX660 (tolinapant) in combination with eribulin mesylate (eribulin) in treating patients with triple negative breast cancer that cannot be removed by surgery (unresectable) or that has spread to nearby tissues or lymph nodes… Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Biopsy Procedure, Biospecimen Collection and Computed Tomography
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
4 Aug 2025to 17 May 2027
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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically or cytologically confirmed invasive breast carcinoma.
  • We limit the molecular subtype to triple negative (TNBC) and hormone receptor-low and Her2 negative (hormone receptor [HR]-low/Her2[-]) breast cancer. TNBC is defined as: HER2 expression 0 or 1+ on immunohistochemistry (IHC) or non-amplified (defined as HER2/CEP17 ratio < 2 or copy number < 6) on fluorescence in situ hybridization (FISH). If HER2 expression is 2+ on IHC, negative HER2 expression must be confirmed by FISH. Pathologic diagnosis of TNBC (negative HER2 status by cytogenetics, < 1% of cells stained positive for estrogen receptor [ER] by IHC, and < 1% of cells stained positive for progesterone receptor [PR] by IHC) (Allison et al., 2020, Wolff et al., 2013). HR-low/Her2(-) is defined as: HER2 expression 0 or 1+ on IHC or non-amplified (defined as HER2/CEP17 ratio < 2 or copy number < 6) on fluorescence in situ hybridization (FISH). If HER2 expression is 2+ on IHC, negative HER2 expression must be confirmed by FISH. 1-10% of cells stained positive for ER by IHC, and/or 1-10% of cells stained positive for PR by IHC) (Allison et al., 2020, Wolff et al., 2013)
  • Patients must have confirmed locally advanced and unresectable or metastatic disease by either imaging or tissue diagnosis
  • Patients must have received at least 2 lines of systemic treatment for metastatic disease
  • Patients must have measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) criteria
  • Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of ASTX660 (tolinapant) in combination with eribulin mesylate in patients < 18 years of age, children are excluded from this study
Show all 31Show fewer
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
  • Leukocytes ≥ 3,000/mcL
  • Absolute neutrophil count ≥ 1,500/mcL
  • Platelets ≥ 100,000/mcL
  • Hemoglobin ≥ 9 g/dL
  • Total bilirubin ≤ 1.8 mg/dL
  • Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) ≤ 3 x institutional upper limit of normal (ULN) or ≤ 5 x institutional ULN if known liver metastases
  • Alkaline phosphatase ≤ 3 x institutional ULN or ≤ 5 x institutional ULN if known liver and/or skeletal metastases
  • Lipase ≤ 1.5 x ULN
  • Creatinine ≤ 1.5 x institutional ULN OR glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m^2
  • International normalized ratio (INR) ≤ 1.5 x ULN
  • Partial thromboplastin time (PTT) ≤ 1.5 x ULN
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial provided they are on a stable regimen of anti-retroviral therapy (ART) with no medications otherwise prohibited by this protocol (e.g., drug-drug interactions)
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after central nervous system (CNS)-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period
  • Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better. Patients with history of known congestive heart failure (left ventricular ejection fraction [LVEF] < 50%) must have documented LVEF ≥ 50% within 12 months of study enrollment
  • Patients with history of known type I or type II diabetes must have a fasting glucose level of < 120 mg/dL on at least 2 separate occasions or glycosylated hemoglobin (HbA1c) < 8.5% at screening within 14 days prior to registration
  • Patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that their medication dose and INR/PTT is stable
  • Prophylactic antiemetics may be administered according to standard practice. The routine use of standard antiemetics, including 5-HT3 blockers, such as granisetron, ondansetron, or an equivalent agent, is allowed as needed, as long as corrected QT (QTc) interval on baseline electrocardiogram (ECG) < 480 msec
  • Patients must be willing to have biopsies for this study in order to be enrolled in the dose expansion
  • The effects of ASTX660 (tolinapant) on the developing human fetus are unknown. For this reason and because dual IAP antagonist agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential must agree to practice 1 highly effective contraceptive measure of birth control (with a failure rate of < 1% per year; preferably with low user dependency) during the study and for 6 months after the last dose of study treatment and must agree not to become pregnant for 6 months after completing treatment. Men with female partners of childbearing potential must agree to use a condom and advise their partners to practice 1 highly effective contraceptive measure of birth control (user dependent or with low user dependency) during the study and for at least 3 months after completing treatment, and must agree not to father a child while receiving study treatment and for at least 3 months after completing treatment
  • Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants

Who cannot join

  • Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia
  • Patients who are receiving any other investigational agents or concurrent anticancer therapy
  • Patients who have had prior treatment with eribulin mesylate
  • Patients with pre-existing neuropathy of grade 2 or higher
  • Myeloid growth factors within 7 days prior to treatment start
  • Platelet transfusion within 7 days prior to treatment start
Show all 21Show fewer
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ASTX660 (tolinapant) or other agents used in study
  • Immunosuppressive therapy is not allowed while on study
  • Systemic corticosteroid therapy at a daily dose higher than 15 mg prednisone or equivalent is not permitted while on study. Previous corticosteroid therapy must be stopped or reduced to the allowed dose at least 7 days prior to the CT/MRI screening. If a patient is on chronic corticosteroid therapy, corticosteroids should be de-escalated to the maximum allowed dose before the screening. Patients may be using topical or inhaled corticosteroids. Short-term (up to 7 days) systemic corticosteroids above 15 mg prednisolone or equivalent will be allowed for the management of acute conditions (e.g., treatment non-infectious pneumonitis)
  • Patients with non-healing wound, ulcer, or bone fracture. Patients with compression or pathologic fractures that are stable in the opinion of the investigator may be enrolled, as long as the bone fracture is not felt to pose a high likelihood of treatment delay or difficulties in treatment adherence as per the judgement of the investigator
  • Patients with active, clinically serious infections > grade 2 (Common Terminology Criteria for Adverse Events [CTCAE] version [v]5.0) (viral, bacterial or fungal infection)
  • History of known pneumocystis jiroveci pneumonia (PJP) infection or documented non-infectious pneumonitis/interstitial lung disease (ILD)
  • Patients with arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before the start of study medication
  • Uncontrolled hypertension (defined as blood pressure ≥ 150/90 mm/Hg) despite optimal medical management (per investigator's opinion)
  • Proteinuria as estimated by urine protein/creatinine ratio > 3.5 g/g on random urine sample or grade ≥ 3 as assessed by 24-hour urine protein collection
  • Patients with history of, or current uncontrolled autoimmune disease. Patients who have adrenal or pituitary insufficiency who are stable on replacement therapy (i.e., thyroxine or physiologic corticosteroid replacement therapy that meets concomitant medication restrictions) are allowed
  • Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
  • Pregnant women are excluded from this study because ASTX660 (tolinapant) and eribulin mesylate are anti-cancer agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ASTX660 (tolinapant) and eribulin mesylate, breastfeeding should be discontinued until 2 weeks after the mother's last dose of study drugs
  • The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest
  • Patients with congenital long QT syndrome, bradyarrhythmias, or taking drugs known to prolong the QT interval
  • Patients unable to stop using any medication which is a moderate or strong CYP3A4 inhibitor or inducer within 2 weeks of the start of the study

About this study

Official title: Phase I/Ib Study of Eribulin in Combination With ASTX660 (Tolinapant) in Metastatic Triple Negative Breast Cancer (TNBC)

This phase I/Ib trial tests the safety, side effects, best dose, and effectiveness of ASTX660 (tolinapant) in combination with eribulin mesylate (eribulin) in treating patients with triple negative breast cancer that cannot be removed by surgery (unresectable) or that has spread to nearby tissues or lymph nodes (locally advanced) or to other places in the body (metastatic). Tolinapant may stop the growth of tumor cells by blocking proteins, such as XIAP and cIAP1, needed for tumor cell survival. Chemotherapy drugs, such as eribulin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving tolinapant in combination with eribulin may be safe, tolerable, and/or effective in treating patients with unresectable, locally advanced, or metastatic triple negative breast cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the safety and tolerability of ASTX660 (tolinapant) in combination with eribulin in patients with metastatic breast cancer.

II. Determine the maximum tolerated dose (MTD) of ASTX660 (tolinapant) in combination with eribulin.

SECONDARY OBJECTIVES:

  1. To observe and record anti-tumor activity. II. Determine the pharmacokinetic parameters of ASTX660 (tolinapant) and eribulin when used in combination.

III. Determine the pharmacodynamic parameters of antitumor activity of ASTX660 (tolinapant) and eribulin combination.

EXPLORATORY OBJECTIVES:

  1. Develop biomarkers predictive of response and resistance to ASTX660 (tolinapant) in combination with eribulin in metastatic triple negative breast cancer.

II. Investigate biomarkers and mechanisms of primary and secondary resistance to ASTX660 (tolinapant) in combination with eribulin in metastatic triple negative breast cancer.

OUTLINE: This is a dose-escalation study of tolinapant in combination with eribulin followed by a dose-expansion study.

Patients receive tolinapant orally (PO) once daily (QD) on days 1-7 and 15-21 and eribulin intravenously (IV) over 2-5 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, tissue biopsy, chest X-ray, and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study.

After completion of study treatment, patients are followed for up to 3 months.

Being tested
Biopsy Procedure, Biospecimen Collection, Computed Tomography, Eribulin Mesylate, Magnetic Resonance Imaging
Medical subject headings
Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biopsy ProcedureProcedure or surgery

    Also called Biopsy, BIOPSY_TYPE, Bx

    Undergo tissue biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • Eribulin MesylateDrug

    Also called B1939 Mesylate, E7389, ER-086526 Mesylate, Halaven

    Given IV

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • TolinapantDrug

    Also called ASTX 660, ASTX660, XIAP/cIAP1 Antagonist ASTX660

    Given PO

  • X-Ray ImagingProcedure or surgery

    Also called Conventional X-Ray, Diagnostic Radiology, Medical Imaging, X-Ray, Plain film radiographs

    Undergo chest X-ray

Study groups in NCT06590558
Study groupRoleWhat they receive
Treatment (tolinapant, eribulin)ExperimentalPatients receive tolinapant PO QD on days 1-7 and 15-21 and eribulin IV over 2-5 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, tissue biopsy, chest X-ray, and CT or MRI throughout the study.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Eribulin Mesylate; Procedure: Magnetic Resonance Imaging; Drug: Tolinapant; Procedure: X-Ray Imaging

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of adverse events (AEs)

    Medical Dictionary for Regulatory Activities (MedDRA) terms will be used to characterized AEs which will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. Descriptive statistics will be used to report the frequency according to severity of the AEs.

    Measured: Up to 3 months after last dose of study drug

  2. Dose-limiting toxicities (DLT)

    MedDRA terms will be used to characterized the AEs which will be graded according to the NCI CTCAE v5.0. Descriptive statistics will be used to report the frequency according to the severity of the AEs.

    Measured: Up to 4 weeks following the first administration (cycle 1 day 1) of the investigational therapy

  3. Maximum tolerated dose (MTD)

    The MTD will be defined as the highest dose at which 0 out of first 3 or 1 out of total of 6 patients experience a DLT during the first cycle of therapy, collectively 4 weeks of the investigational therapy.

    Measured: Up to 4 weeks

Secondary outcomes (10)

  1. Overall response rate (ORR)

    The best ORR is the best response recorded from the start of the treatment until disease progression/recurrence. Will be estimated along with two-sided 95% confidence intervals with the exact method of Clopper-Pearson intervals for all evaluable patients who received the investigational therapy as well as for all evaluable patients who received the investigational therapy at the MTD.

    Measured: At start of treatment until disease progression/recurrent, assessed up to 3 years

  2. Duration of response (DOR)

    DOR will be measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. DOR will be analyzed using the Kaplan-Meier method.

    Measured: At complete response (CR) or partial response (PR) to recurrent or progressive disease, assessed up to 3 years

  3. Progression-free survival (PFS)

    PFS will be defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. PFS will be analyzed using the Kaplan-Meier method.

    Measured: At start of treatment to progression or death, assessed up to 3 years

  4. Overall survival (OS)

    OS will be defined as the duration of time from start of treatment to time of death of any cause. OS will be analyzed using the Kaplan-Meier method.

    Measured: At start of treatment to death, assessed up to 3 years

  5. Maximum concentration (Cmax) of ASTX660 (tolinapant) and eribulin

    Cmax will be derived from the measured concentrations of eribulin and tolinapant by performing noncompartmental analysis or pharmacometrics. Descriptive statistics will be used to report pharmacokinetics.

    Measured: Up to day 8

  6. Time of maximum concentration (Tmax) of ASTX660 (tolinapant) and eribulin

    Tmax will be derived from the measured concentrations of eribulin and tolinapant by performing noncompartmental analysis or pharmacometrics. Descriptive statistics will be used to report pharmacokinetics.

    Measured: Up to day 8

  7. Area under the curve (AUC) of ASTX660 (tolinapant) and eribulin

    AUC will be derived from the measured concentrations of eribulin and tolinapant by performing noncompartmental analysis or pharmacometrics. Descriptive statistics will be used to report pharmacokinetics.

    Measured: Up to day 8

  8. Half Tmax (T½) of ASTX660 (tolinapant) and eribulin

    T½ will be derived from the measured concentrations of eribulin and tolinapant by performing noncompartmental analysis or pharmacometrics. Descriptive statistics will be used to report pharmacokinetics.

    Measured: Up to day 8

  9. Clearance of ASTX660 (tolinapant) and eribulin

    Clearance will be derived from the measured concentrations of eribulin and tolinapant by performing noncompartmental analysis or pharmacometrics. Descriptive statistics will be used to report pharmacokinetics.

    Measured: Up to day 8

  10. Change in cleaved caspase 3 levels

    Change in cleaved caspase 3 levels assessed in an apoptosis multiplex immunoassay on a Luminex platform in paired pre- and on-treatment tumor biopsies. The measured levels of caspase 3 in paired pre- and on-treatment biopsies will be compared using a nonparametric paired t-test.

    Measured: At pre-study and at week 5

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Sep 2024
  2. Study start4 Aug 2025 (estimated)
  3. Primary completion17 May 2027 (estimated)
  4. Study completion17 May 2027 (estimated)

Why it stopped: Manually added per CS0177524- Weekly CTEP status report.

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06590558
Sponsor's protocol ID
NCI-2024-05666
Other IDs
NCI-2024-05666, 10647, 10647, UM1CA186712
Status last verified
Jul 2025
First submitted
6 Sep 2024
Last updated
3 Jul 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Anatomic Stage III Breast Cancer AJCC v8 and Anatomic Stage IV Breast Cancer AJCC v8, run by National Cancer Institute (NCI).

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 31 inclusion and 21 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: withdrawn, as of the sponsor's last update on 3 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

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 withdrawn before enrolling participants, so there are no results.

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?

Incidence of adverse events (AEs) (time frame: Up to 3 months after last dose of study drug). 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 NCT06590558.

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 3 Jul 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in