Dose-escalation Study to Assess Safety and Pharmacokinetics of Nab-Sirolimus in Patients With Locally Advanced or Metastatic Solid Tumors and Moderate Liver Impairment

NCT05661461 | Recruiting Phase 1 FDA Drug

• 1 other identifier: HEP-001
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase 1, multi-center, open-label, dose-escalation study of nab-sirolimus in adult patients with locally advanced or metastatic solid tumors and moderate hepatic impairment or normal hepatic function.

Conditions

Tumor, Solid; Tumor; Advanced Solid Tumor

Outcome Measures

Primary Outcomes (4)

• MTD for patients with moderate hepatic impairment

  Through Day 22

• Maximum concentration (Cmax)

  Time 0

• Area under the serum concentration-time curve

  Time 0 to time of the last quantifiable concentration (AUC 0-last)

• Area under the serum concentration-time curve

  Time 0 to 168 hours (AUC 0-168)

Secondary Outcomes (10)

• Area under the serum concentration-time curve

  Time 0 extrapolated to infinity (AUC0-inf)

• Time to maximum observed serum concentration (T max)

  Time 0 to 168 hours (AUC 0-168)

• Clearance (CL)

  Time 0 to 168 hours (AUC 0-168)

• Total volume of distribution during the terminal phase (V z )

  Time 0 to 168 hours (AUC 0-168)

• Steady-state volume of distribution (V ss)

  Time 0 to 168 hours (AUC 0-168)

Study Arms (1)

Experimental

EXPERIMENTAL

nab-Sirolimus

Drug: nab-sirolimus

Interventions

nab-sirolimus DRUG

This is a phase 1, multi-center, open-label, dose-escalation study of nab-sirolimus in adult patients with locally advanced or metastatic solid tumors and moderate hepatic impairment or normal hepatic function.

Also known as: ABI-009, nab-rapamycin, albumin-bound rapamycin

Experimental

Eligibility Criteria

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

You may qualify if:

• For All Patients
• Willing and able to provide informed consent and comply with protocol requirements for the duration of the study.
• Male or female patients at least 18 years of age at the time of signing the informed consent form.
• Histologically confirmed locally advanced or metastatic solid tumors that is measurable or non-measurable.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
• Adequate hematologic counts:
• Absolute neutrophil count (ANC) ≥1.0 × 109 /L (growth factor support allowed)
• Platelet count ≥75,000/mm 3 (75 × 10 9 /L) (transfusion and/or growth factor support allowed)
• Hemoglobin ≥8.0 g/dL (transfusion and/or growth factor support allowed)
• Creatinine clearance ≥30 mL/min as assessed by the Cockcroft-Gault equation:
• Creatinine Clearance ≥30 = (140 - age) × (weight\[kg\] / (72 x SCr\[mL/min\]\_ x 0.85, if female
• Fasting serum triglyceride must be ≤300 mg/dL; fasting serum cholesterol must be
• ≤350 mg/dL.
• Male or non-pregnant and non-breastfeeding female:
• Females of child-bearing potential must agree to use highly effective contraception or abstinence without interruption from 28 days prior to first dose throughout 3 months after last dose and have a negative pregnancy test (urine or serum) result at screening and after the end of study treatment. A second form of birth control is required even if she has had a tubal ligation.

You may not qualify if:

• Received prior treatment with an mTOR inhibitor within 4 weeks prior to first dose.
• Patients who have any severe and/or uncontrolled medical or psychiatric conditions or other conditions that could affect their participation including:
• Patients with meningeal carcinomatosis, leptomeningeal carcinomatosis, spinal cord compression, untreated brain metastases or symptomatic or unstable brain metastases. Note: Patients with stable brain metastases (defined as asymptomatic or no requirement for high-dose \[defined as dexamethasone 10 mg daily or higher\] or increasing dose of systemic corticosteroids) and without imminent need of radiation therapy are eligible. If applicable, patients must have completed brain radiation therapy and recovered adequately from any associated toxicity and/or complications prior to eligibility assessment. For patients who have received prior radiation therapy, post-treatment magnetic resonance imaging (MRI) scan should show no increase in brain lesion size/volume.
• Unstable angina pectoris, symptomatic congestive heart failure (New York Heart Association, NYHA class III or IV), myocardial infarction ≤6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease.
• Pre-existing severely impaired lung function. If a patient has a pre-existing pulmonary condition, eligible patients should have a spirometry and diffusing capacity for carbon monoxide (DLCO) that is \>50% of the normal predicted value and/or O2 saturation that is \>88% at rest on room air (Note: spirometry and pulmonary function tests \[PFTs\] not required to be performed unless clinically indicated).
• Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy. Note, controlled non melanoma skin cancers, carcinoma in situ of the cervix, resected incidental prostate cancer, or other adequately treated carcinoma-in-situ may be eligible, after documented discussion with the Medical Monitor.
• Uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg).
• Patients with history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension.
• Individuals with known human immunodeficiency virus (HIV) infection are excluded from this study as combination antiretroviral therapy could potentially result in significant pharmacokinetic interactions. In addition, these individuals are at increased risk of serious infections due to the immunosuppressive effects of mTOR inhibition.
• Active Hepatitis B or Hepatitis C, with detectable viral load. Note: A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients.
• Have active severe (Grade ≥3) infection requiring intravenous (IV) antibiotics (contact medical monitor for clarification).
• High-dose systemic corticosteroids (\>10 mg of prednisone or its equivalent) are not permitted within 2 weeks of first dose. However, inhaled, intranasal, intra articular, and topical steroids are allowed.
• Have a history of Gilbert's disease.
• Any condition that in the opinion of the Investigator would place the patient at an unacceptable risk or cause the patient to be unlikely to fully participate or comply with study procedures.
• For Patients with Moderate Hepatic Impairment

Sponsors & Collaborators

• Aadi Bioscience, Inc.: lead

Study Sites (2)

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, 78229, United States

RECRUITING

START Mountain Region

West Valley City, Utah, 84119, United States

RECRUITING

MeSH Terms

Conditions

Neoplasms

Central Study Contacts

Aadi Medical Information

CONTACT

1-888-246-2234; MedInfo@aadibio.com

Study Design

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

Study Record Dates

• First Submitted: December 14, 2022
• First Posted: December 22, 2022
• Study Start: November 23, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: November 13, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)