Trial of Nab-sirolimus in Patients With Well-differentiated Neuroendocrine Tumors (NETs) of the Gastrointestinal Tract, Lung, or Pancreas Who Have Not Received Prior Treatment With mTOR Inhibitors

A Phase 2 Multi-center, Open-label, Single Arm Study of Nab-sirolimus in Patients With Well-differentiated Neuroendocrine Tumors (NETs) of the Gastrointestinal Tract, Lung, or Pancreas Who Have Not Received Prior Treatment With mTOR Inhibitors

A Phase 2 multi-center, open-label, single arm study of nab-sirolimus in patients with well-differentiated neuroendocrine tumors (NETs) of the gastrointestinal tract, lung, or pancreas who have not received prior treatment with mTOR inhibitors

Study Overview

• Status: Completed
• Conditions: Neuroendocrine Tumors; Pancreatic Neuroendocrine Tumor; Gastrointestinal Neuroendocrine Tumor; NET; Pulmonary Neuroendocrine Tumor
• Intervention / Treatment: Drug: nab-sirolimus

Detailed Description

This is a prospective phase 2 single arm, open-label, multi-institutional study to determine the efficacy and safety prospective of nab-sirolimus and patients with functional or non-functional, well-differentiated, locally advanced unresectable in metastatic NETs of the GI tract, lung, or pancreas.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Newport Beach, California, United States, 92663
      • Hoag Memorial Hospital Presbyterian
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with functional or non-functional, well-differentiated, locally advanced unresectable or metastatic NETs of the GI tract, lung, or pancreas who have received 2 or less prior lines of therapy excluding somatostatin analogs

2. Patients with functional NETs may enroll if:

   1. the patient has been on a stable dose of an somatostatin analogs for ≥12 weeks and
   2. the patient has experienced disease progression while on stable somatostatin analogs dose
3. Patients must have 1 or more measurable target lesions by RECIST v1.1
4. Age: 18 years or older
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 or Karnofsky Performance Status (KPS) ≥80

6. Adequate liver function:

   1. Total bilirubin ≤1.5 × upper limit of normal (ULN) (unless due to Gilbert's syndrome or attributable to liver metastases, then ≤3 × ULN)
   2. Aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤2.5 × ULN (≤5 × ULN if attributable to liver metastases)
7. Adequate renal function: creatinine clearance ≥30 mL/min, Cockcroft-Gault creatinine clearance = ((140-age) × weight[kg]) / (72 × serum creatinine [mL/min]) × 0.85, if female.

8. Adequate hematologic parameters:

   1. Absolute neutrophil count (ANC) ≥1.0 × 10^9/L (growth factor support allowed)
   2. Platelet count ≥100,000/mm^3 (100 × 10^9/L) (transfusion and/or growth factor support allowed)
   3. Hemoglobin ≥8.0 g/dL (transfusion and/or growth factor support allowed)
9. Fasting serum triglyceride must be ≤300 mg/dL; fasting serum cholesterol must be less than or equal to 350 mg/dL
10. Minimum of 4 weeks since any major surgery, completion of radiation, and adequately recovered from the acute toxicities of any prior therapy, including neuropathy, to Grade ≤1

11. Male or non-pregnant and non-breastfeeding female:

    1. Females of childbearing potential must agree to use effective contraception or abstinence without interruption from 28 days prior to starting study medication throughout 3 months after last dose of study medication and have a negative serum pregnancy test (beta human chorionic gonadotropin [β-hCG]) result at screening and agree to ongoing pregnancy testing during the course of the study, and after the EOS treatment. A second form of birth control is required even if she has had a tubal ligation.
    2. Male patients must agree not to donate sperm and must practice abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study and throughout 3 months after last dose of study medication. A second form of birth control is required even if he has undergone a successful vasectomy.
    3. Sexual abstinence is considered a highly effective contraceptive method only if defined as refraining from heterosexual intercourse from 28 days prior to starting study medication throughout 3 months after last dose of study medication. The reliability of sexual abstinence should be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the patient.
12. The patient or the patient's legal guardian(s) understand(s) and sign(s) the informed consent
13. Willingness and ability to comply with scheduled visits, laboratory tests, and other study procedures

14. Patients with a known history of human immunodeficiency virus (HIV) infection are eligible if:

    1. There has been no acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection in 12 months prior to enrollment.
    2. The patient has been receiving an antiretroviral therapy regimen for ≥4 weeks and the HIV viral load is <400 copies/mL prior to enrollment.
    3. Antiretroviral therapy regimen does not include strong cytochrome (CYP)3A4 inhibitors or inducers

Exclusion Criteria:

1. Prior treatment with mTOR inhibitors including nab-sirolimus

   Note: Patients who have previously received locoregional or liver-directed therapies (radiofrequency or microwave ablation, transarterial chemoembolization, etc.) are eligible to enroll in the study.

2. Patients with functional NETs who are experiencing uncontrolled symptoms attributed to hormones and other vasoactive substances secreted by the tumor
3. Patients with inactivating TSC1 or TSC2 alterations (based on tissue or liquid NGS)
4. Severe (Grade ≥3) ongoing infection requiring parenteral or oral anti-infective treatment, either ongoing or completed ≤7 days prior to enrollment

5. Patients who have any severe and/or uncontrolled medical or psychiatric conditions or other conditions that could affect their participation including:

   1. Known or suspected brain metastases
   2. Severe heart disease defined as unstable angina pectoris, NYHA Class III or IV congestive heart failure, myocardial infarction ≤6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease.

   3. Severe lung disease defined as a diffusing capacity for carbon monoxide that is ≤50% of normal predicted value and/or an O2 saturation ≤88% at rest on room air

      (Note: Spirometry and pulmonary function tests are not required to be performed unless clinically indicated.)

   4. Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy
   5. A history of malignancies other than the one under treatment unless the patient is disease-free for more than 5 years from diagnosis. Controlled non-melanoma skin cancers, carcinoma in situ of the cervix, resected incidental prostate cancer, certain low-grade hematologic malignancies (eg, chronic lymphocytic leukemia, follicular lymphoma, etc), or other adequately treated carcinoma in situ may be eligible, after discussion with the medical monitor.
   6. Uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg)
   7. Patients with history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension
   8. Active Hepatitis B and/or Hepatitis C infection and detectable viral load despite antiviral therapy.
6. Required use of concomitant medications with strong CYP3A4 interactions (induction or inhibition) should be discontinued (strong inhibitors include ketoconazole, itraconazole, voriconazole, erythromycin, clarithromycin, telithromycin; strong inducers include rifampin and rifabutin). These agents must be discontinued prior to first dose of nab-sirolimus.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: neuroendocrine tumors; Patients with well-differentiated neuroendocrine tumors of the gastrointestinal tract, lung, or pancreas.	Drug: nab-sirolimus; Prospective phase 2 single arm, open-label, multi-institutional study to determine the efficacy and safety prospective of nab-sirolimus administered by IV infusion; Other Names: ABI-009

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Objective Response Rate	Objective Response Rate (ORR) is defined as the proportion of patients with best overall response (BOR) of confirmed partial response (PR) or complete response (CR) from the time of study treatment initiation until progression of disease (PD) as determined by the Investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Progression (PD) is defined per RECIST v1.1 as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or the appearance of one or more new lesions.	From the start of study treatment to radiographically confirmed disease progression (PD) per RECIST v1.1, assessed at screening, every 6 weeks (±7 days) for the first 12 weeks, and every 12 weeks (±7 days) thereafter, up to 22 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events.	The percentage of participants experiencing at least one treatment-emergent adverse event (TEAE) and treatment-related adverse event. Adverse events are defined as treatment-emergent (TEAEs) if they began or worsened on or after the first administration of study drug through 28 days after the last administration. Severity of adverse events is graded per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.	From first dose of study treatment through end of treatment (estimated up to 18 months) plus safety follow-up of 30 days after the last dose.
Duration of Response (DOR)	Duration of Response (DOR) is determined for patients with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR), defined as the time from the scan first showing response by RECIST v1.1 to disease progression (PD) or death from any cause. Progression (PD) is defined per RECIST v1.1 as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or the appearance of one or more new lesions.	From first documented response (CR or PR) to radiographically confirmed disease progression (PD) per RECIST v1.1 or death from any cause, assessed at screening, every 6 weeks for the first 12 weeks, and every 12 weeks thereafter, up to 22 months
Disease Control Rate (DCR)	Disease Control Rate (DCR) is defined as the proportion of patients achieving a best overall response (BOR) of confirmed complete response (CR), partial response (PR) (either of any duration), or stable disease (SD) lasting >=12 weeks by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 following study treatment initiation. Progression (PD) is defined per RECIST v1.1 as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or the appearance of one or more new lesions.	From the start of study treatment to radiographically confirmed disease progression (PD) per RECIST v1.1, assessed at screening, every 6 weeks for the first 12 weeks, and every 12 weeks thereafter, up to 22 months
Time to Response (TTR)	Time to Response (TTR) is defined as the time from the first dose of study medication to the initial measurement of complete response (CR) or partial response (PR), where CR or PR is subsequently confirmed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Progression (PD) is defined per RECIST v1.1 as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or the appearance of one or more new lesions.	From the first dose of study treatment to the initial documentation of complete response (CR) or partial response (PR) per RECIST v1.1 , assessed at screening, every 6 weeks for the first 12 weeks, and every 12 weeks thereafter, up to 22 months
Progression-free Survival（PFS）	Number of months from study treatment initiation to the date of disease progression or death due to any cause	From first dose of study treatment until the date of first documented disease progression or death from any cause, whichever occurs first, assessed every 6 weeks for the first 12 weeks and every 12 weeks thereafter, up to approximately 21 months
Overall Survival（OS）	Number of months from study treatment initiation to the date of death due to any cause	From first dose of study treatment until the date of death from any cause, assessed approximately every 12 weeks following the end-of-treatment visit, up to approximately 24 months.

Collaborators and Investigators

• Sponsor: Aadi Bioscience, Inc.
• Investigators: Study Director: Leonor Nazareno, Aadi Bioscience

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2023
• Primary Completion (Actual): October 3, 2025
• Study Completion (Actual): October 3, 2025

Study Registration Dates

• First Submitted: August 10, 2023
• First Submitted That Met QC Criteria: August 10, 2023
• First Posted (Actual): August 18, 2023

Study Record Updates

• Last Update Posted (Actual): August 25, 2026
• Last Update Submitted That Met QC Criteria: July 31, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Pancreatic Neuroendocrine Tumor; NET; nab-sirolimus; ABI-009; FYARRO; Neuroendocrine Tumors; Gastrointestinal Neuroendocrine Tumor; Pulmonary Neuroendocrine Tumor
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplasms, Glandular and Epithelial; Adenoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Pancreatic Neoplasms; Neuroendocrine Tumors; Adenoma, Islet Cell; Gastro-enteropancreatic neuroendocrine tumor; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: NET-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No