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Advanced Malignant Solid NeoplasmPhase 1NCT03725436

ALRN-6924 and Paclitaxel in Treating Patients With Advanced, Metastatic, or Unresectable Solid Tumors

A Phase 1 study testing MDM2/MDMX Inhibitor ALRN-6924 and Paclitaxel in people with Advanced Malignant Solid Neoplasm and Anatomic Stage III Breast Cancer AJCC v8, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase Ib trial studies the side effects and best dose of ALRN-6924 when given together with paclitaxel in treating patients with solid tumors that have spread to other places in the body or cannot be removed by surgery. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
MDM2/MDMX Inhibitor ALRN-6924 and Paclitaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
1 siteUnited States
Study dates
24 Jan 2019to 11 Mar 2026
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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • In order to be eligible to participate in this study, an individual must meet all of the following criteria:
  • 18 years of age or older
  • Histologically- or cytologically-confirmed solid tumors (excluding lymphomas) that are metastatic or unresectable and that meet the following criteria:
  • Escalation and expansion cohorts: wild type (WT) TP53 status defined as no mutation on a Clinical Laboratory Improvement Amendments (CLIA)-certified next-generation sequencing (NGS) assay that has sequenced the full length TP53 gene. Patients can be enrolled based on tissue testing or liquid biopsies. If enrolled based on liquid biopsies, testing should have detected other somatic mutations.
  • Expansion cohort A only: estrogen receptor (ER) positive (> 1%), human epidermal growth factor 2 (HER2) negative, WT TP53 metastatic or inoperable locally advanced or locally recurrent breast cancer regardless of progresterone receptor (PR) status, HER2 status will be defined according to the ASCO/CAP 2018 recommendationa (Patients can be HER2 0+ or 1+ by immunohistochemistry (IHC), 2+ by IHC and fluorescent in situ hybridization (FISH) non-amplified to be considered HER2 negative). Standard treatment with therapies known to confer a survival benefit does not exist, is no longer effective or tolerated, or the patient declines standard treatment. For the dose expansion cohort only, breast cancer patients with ER+, HER2- status must have received prior endocrine therapy and CDK4/6 inhibitors
  • Expansion cohort B only: advanced or metastatic solid tumors with MDM2 or MDM4 amplifications and WT TP53 metastatic for which standard treatment with therapies known to confer a survival benefit does not exist, is no longer effective or tolerated, or the patient declines standard treatment.
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  • Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. In the dose escalation stage, patients without measurable disease by RECIST 1.1, but evaluable disease are also eligible.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (see Section 12, Appendix A).
  • Demonstrate adequate organ function as defined by the parameters listed below:
  • Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or ≥ 45 mL/min/1.73m2 by CKD-EPI equation for subjects with creatinine levels > 1.5 x institutional ULN.
  • Total bilirubin ≤ 1.5 x ULN, or direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 x ULN, or unless due to Gilbert's Syndrome.
  • Alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) ≤ 2.5 x ULN or ≤ 5 x ULN if hepatic abnormalities are related to underlying liver metastases or liver/biliary primary.
  • Absolute neutrophil count (ANC) ≥1500/mm3(without G-CSF in the 2 weeks prior to treatment start)
  • Platelet count ≥ 100,000/mm3
  • Hemoglobin ≥ 9 g/dL (without blood transfusion in the 2 weeks prior to treatment start)
  • All patients (males and females) of childbearing potential must agree to use medically effective contraception during the study and for 6 months after the last dose of study drugs. A negative urine or serum pregnancy test in women of childbearing potential is required within 72 hours prior to first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Have no concomitant medical condition (including, but not limited to, ongoing or active infection or any psychiatric disorder), that in the judgment of the investigator will interfere with the patient's ability to participate in the study or render such participation medically inappropriate.
  • No medical history of another cancer (except basal or squamous cell skin cancer or in situ cervical cancer, or carcinomas in situ or other malignancies with a ≥95% 5-year survival) within 2 years of the start of study treatment.
  • No investigational drug or other anticancer treatments (including chemotherapy or radiation, except palliative radiation) within 21 days or at least 5 half-lives, whichever is shorter, of the start of the study treatment. No palliative radiation within 2 weeks prior to the start of the study treatment. Supportive treatments such as LHRH agonists can be continued for patients with castration-resistant prostate cancer or pre-menopausal breast cancer while on treatment.
  • No major surgery within 1 month of treatment and fully recovered.
  • Willing and able to provide informed consent.

Who cannot join

  • An individual who meets any of the following criteria will be excluded from participation in this study:
  • Previous treatment with investigational agents that inhibit MDM2 or MDMX activity.
  • Known active hepatitis B, hepatitis C and/or human immunodeficiency virus (HIV)-positive patients who have a cluster of differentiation 4 (CD4) count < 200. No antiretroviral medications that are CYP3A4 substrates will be allowed.
  • Pre-existing history of or known cardiovascular risk:
  • History of acute coronary syndromes within 6 months prior to the first dose of ALRN-6924 (including myocardial infarction, unstable angina, coronary artery bypass graft, angioplasty, or stenting).
  • Uncontrolled hypertension
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  • Pre-existing cardiac failure (New York Heart Association class III-IV)
  • Clinically significant uncontrolled arrhythmias
  • Corrected QTcF interval on screening ECG ≥450 msec for males and ≥470 msec for females (QTcF >480 msec for any patient with a bundle branch block).
  • Clinically significant gastrointestinal bleeding within 6 months prior to the start of study treatment.
  • Females who are pregnant or nursing.
  • Symptomatic central nervous system (CNS) metastases by history, clinical signs or radiologic findings. Patients with previously treated brain metastases are eligible if clinically stable and off steroid treatment for 2 weeks prior to study enrollment. Patients with new or progressive brain metastases (active brain metastases) are eligible if the treating physician determines that immediate CNS specific treatment is not required.
  • Known hypersensitivity to any study drug component.
  • The required use of any concomitant medications that are predominantly cleared by hepatobiliary transporters, OATP members OATP1B1 and OATP1B3, on the day of the ALRN-6924 infusion or within 48 hours after an ALRN-6924 infusion.
  • Patients with Grade ≥2 neuropathy will be excluded.
  • Patients with a known Human Papilloma Virus (HPV)-positive malignancy will be excluded from enrollment. This is owing to the fact that HPV-infected tumor cells continue to express the viral E6 protein, which is known to cause degradation of p53, hence rendering the expected ALRN-6924 - mediated dual inhibition of MDM2/MDMX very unlikely to restore p53 function.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase 1b Study of ALRN-6924 in Combination With Paclitaxel in Wild-Type TP53 Advanced or Metastatic Solid Tumors Including Estrogen-Receptor Positive Breast Cancer

This phase Ib trial studies the side effects and best dose of ALRN-6924 when given together with paclitaxel in treating patients with solid tumors that have spread to other places in the body or cannot be removed by surgery. Drugs used in chemotherapy, such as ALRN-6924 and paclitaxel, 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.

Read the detailed description

Primary Objectives:

  • Determine the dose-limiting toxicities (DLT) and the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of ALRN-6924 in combination with paclitaxel in adult patients with advanced or metastatic solid tumors with wild-type (WT) TP53.
  • Evaluate the safety and tolerability of ALRN-6924 in combination with paclitaxel in patients with advanced or metastatic WT TP53 solid tumors.

Secondary Objective:

  • Evaluate the anti-tumor activity of ALRN-6924 in combination with paclitaxel in solid tumors (in dose escalation) and hormone-receptor positive breast cancer (in expansion).

Exploratory objective:

  • Assess predictive and pharmacodynamic (PD) markers of response.
  • Assess the effects of ALRN-6924 and paclitaxel on cell proliferation and apoptosis.
  • Assess the effects of ALRN-6924 and paclitaxel on cell-free DNA (cfDNA) dynamics and macrophage inhibitory cytokine-1 (MIC-1)

OUTLINE: This is a dose-escalation study of MDM2/MDMX inhibitor ALRN-6924.

Patients receive paclitaxel intravenously (IV) over 1 hour and MDM2/MDMX inhibitor ALRN-6924 IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months for 1 year and then every 3 months thereafter.

Being tested
MDM2/MDMX Inhibitor ALRN-6924, Paclitaxel
Medical subject headings
Neoplasm Metastasis, Breast Neoplasms

What participants receive

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

  • MDM2/MDMX Inhibitor ALRN-6924Drug

    Also called ALRN-6924

    Given IV

  • PaclitaxelDrug

    Also called Anzatax, Asotax, Bristaxol, Praxel

    Given IV

Study groups in NCT03725436
Study groupRoleWhat they receive
Treatment (paclitaxel, ALRN-6924)ExperimentalPatients receive paclitaxel IV over 1 hour and MDM2/MDMX inhibitor ALRN-6924 IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: MDM2/MDMX Inhibitor ALRN-6924; Drug: Paclitaxel

What is being measured

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

  1. Maximum tolerated dose (MTD) of combination of ALRN-6924 and paclitaxel, defined as the isotonic estimate of the toxicity rate closest to 0.30

    Measured: Up to 28 days

Secondary outcomes (6)

  1. Objective response rate (ORR) defined as the proportion of patients with complete response (CR) or partial response (PR), as determined by investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST version 1.1)

    Descriptive statistics will be used to summarize all patient data. When applicable, t-tests or Wilcoxon rank-sum tests will be used to make comparisons between patient subgroups of interest for continuous variables for parametric and non-parametric outcomes, respectively. Categorical data will be summarized using frequencies and percentages. Chi-square tests or Fisher's exact tests will be used to make comparisons between patient subgroups of interest for categorical variables. Will be estimated for the expansion cohort of 15 patients treated at the MTD, with corresponding exact 95% confidence intervals.

    Measured: Up to 4 years

  2. Duration of response (DoR)

    Descriptive statistics will be used to summarize all patient data. When applicable, t-tests or Wilcoxon rank-sum tests will be used to make comparisons between patient subgroups of interest for continuous variables for parametric and non-parametric outcomes, respectively. Categorical data will be summarized using frequencies and percentages. Chi-square tests or Fisher's exact tests will be used to make comparisons between patient subgroups of interest for categorical variables. Median DoR will be presented with corresponding Kaplan-Meier curves.

    Measured: Time from documentation of tumor response to disease progression, assessed up to 4 years

  3. Progression-free survival (PFS)

    Descriptive statistics will be used to summarize all patient data. When applicable, t-tests or Wilcoxon rank-sum tests will be used to make comparisons between patient subgroups of interest for continuous variables for parametric and non-parametric outcomes, respectively. Categorical data will be summarized using frequencies and percentages. Chi-square tests or Fisher's exact tests will be used to make comparisons between patient subgroups of interest for categorical variables. Median PFS will be presented with corresponding Kaplan-Meier curves.

    Measured: Time from the start of treatment to disease progression or death, whichever occurs first, assessed up to 4 years

  4. Clinical benefit rate

    Will be defined as the proportion of patients with CR, PR, or stable disease (SD). Descriptive statistics will be used to summarize all patient data. When applicable, t-tests or Wilcoxon rank-sum tests will be used to make comparisons between patient subgroups of interest for continuous variables for parametric and non-parametric outcomes, respectively. Categorical data will be summarized using frequencies and percentages. Chi-square tests or Fisher's exact tests will be used to make comparisons between patient subgroups of interest for categorical variables.

    Measured: At 24 weeks

  5. Overall survival (OS)

    Descriptive statistics will be used to summarize all patient data. When applicable, t-tests or Wilcoxon rank-sum tests will be used to make comparisons between patient subgroups of interest for continuous variables for parametric and non-parametric outcomes, respectively. Categorical data will be summarized using frequencies and percentages. Chi-square tests or Fisher's exact tests will be used to make comparisons between patient subgroups of interest for categorical variables.

    Measured: Time from the start of treatment to death from any cause, assessed up to 4 years

  6. Pharmacokinetics parameters

    Will assess area under the curve (AUC).

    Measured: Up to 4 years

Timeline

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

  1. First posted31 Oct 2018
  2. Study start24 Jan 2019
  3. Primary completion11 Mar 2026
  4. Study completion11 Mar 2026

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
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03725436
Sponsor's protocol ID
2018-0561
Other IDs
NCI-2018-02192, 2018-0561
Status last verified
Mar 2026
First submitted
18 Oct 2018
Last updated
16 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Berglund H, Salomonsson SL, Mohajershojai T, Gago FJF, Lane DP, Nestor M. p53 stabilisation potentiates [177Lu]Lu-DOTATATE treatment in neuroblastoma xenografts. Eur J Nucl Med Mol Imaging. 2024 Feb;51(3):768-778. doi: 10.1007/s00259-023-06462-3. Epub 2023 Oct 12.

    PubMed 37823909

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MDM2/MDMX Inhibitor ALRN-6924 and Paclitaxel in people with Advanced Malignant Solid Neoplasm and Anatomic Stage III Breast Cancer AJCC v8, run by M.D. Anderson Cancer Center at 1 site in United States.

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 21 inclusion and 16 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: finished, as of the sponsor's last update on 16 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 1 site in United States. 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 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Maximum tolerated dose (MTD) of combination of ALRN-6924 and paclitaxel, defined as the isotonic estimate of the toxicity rate closest to 0.30 (time frame: Up to 28 days). 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 NCT03725436, 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 16 Mar 2026.

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