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

NCT03725436 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 2018-0561NCI-2018-02192
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Advanced Malignant Solid Neoplasm; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8; Estrogen Receptor Positive; HER2/Neu Negative; Metastatic Malignant Solid Neoplasm; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8; Recurrent Breast Carcinoma; TP53 wt Allele; Unresectable Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (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

  Up to 28 days

Secondary Outcomes (6)

• 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)

  Up to 4 years

• Duration of response (DoR)

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

• Progression-free survival (PFS)

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

• Clinical benefit rate

  At 24 weeks

• Overall survival (OS)

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

Other Outcomes (8)

• Response

  Up to 4 years

• Gene mutations

  Up to 4 years

• Gene expression profiling

  Up to 4 years

Study Arms (1)

Treatment (paclitaxel, ALRN-6924)

EXPERIMENTAL

Patients 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.

Drug: MDM2/MDMX Inhibitor ALRN-6924; Drug: Paclitaxel

Interventions

MDM2/MDMX Inhibitor ALRN-6924 DRUG

Given IV

Also known as: ALRN-6924

Treatment (paclitaxel, ALRN-6924)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Treatment (paclitaxel, ALRN-6924)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• 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.
• 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)

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Neoplasm Metastasis; Breast Neoplasms

Interventions

Paclitaxel; Taxes

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Study Officials

• Ecaterina E Dumbrava

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2018
• First Posted: October 31, 2018
• Study Start: January 24, 2019
• Primary Completion: March 11, 2026
• Study Completion: March 11, 2026
• Last Updated: March 16, 2026

Record last verified: 2026-03

Locations

US (1)