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

• ClinicalTrials.gov Identifier: NCT05997056
• Recruitment Status: Not yet recruiting
• First Posted: August 18, 2023
• Last Update Posted: August 21, 2023
• Sponsor: Aadi Bioscience, Inc.
• Information provided by (Responsible Party): Aadi Bioscience, Inc.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Neuroendocrine Tumors; NET; Pancreatic Neuroendocrine Tumor; Gastrointestinal Neuroendocrine Tumor; Pulmonary Neuroendocrine Tumor	Drug: nab-sirolimus	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Estimated Study Start Date: December 30, 2023
• Estimated Primary Completion Date: May 9, 2025
• Estimated Study Completion Date: December 8, 2025

Arms and Interventions

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 Name: ABI-009

Outcome Measures

Primary Outcome Measures :

1. Efficacy of nab-sirolimus [ Time Frame: 12 Months ]
   Objective Response Rate (ORR), 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 RECIST v1.1

Secondary Outcome Measures :

1. Incidence and severity of treatment [ Time Frame: 12 Months ]
   Incidence and severity of treatment-emergent and treatment-related adverse events (AEs) as assessed by NCI CTCAE v5.0
2. Duration of response [ Time Frame: 12 Months ]
   Determined for patients with BOR of confirmed CR or PR defined as time from scan first showing response by RECIST v1.1 to PD or death
3. Disease control rate [ Time Frame: 12 Months ]
   BOR of confirmed CR or PR (either of any duration) or stable disease (SD) ≥12 weeks by RECISTv1.1 following study treatment initiation
4. Time to response [ Time Frame: 12 Months ]
   Time from first dose of study medication to initial measurement of CR or PR, where CR or PR is subsequently confirmed by RECIST v1.1
5. Progression-free survival [ Time Frame: 12 Months ]
   Number of months from study treatment initiation to the date of disease progression or death due to any cause
6. Overall survival [ Time Frame: 24 Months ]
   Number of months from study treatment initiation to the date of death due to any cause

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Aadi Bioscience Medical Information; 1-888-246-2234; MedInfo@aadibio.com

Locations

United States, California

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States, 92663

Principal Investigator: Michael Demeure, MD

United States, Colorado

Rocky Mountain Cancer Centers

Denver, Colorado, United States, 80218

Principal Investigator: Allen Cohn, MD

United States, Texas

Texas Oncology

Dallas, Texas, United States, 75246

Principal Investigator: Scott Paulson, MD

Sponsors and Collaborators

Aadi Bioscience, Inc.

Investigators

• Study Director: Willis Navarro, MD; Aadi Bioscience

More Information

• Responsible Party: Aadi Bioscience, Inc.
• ClinicalTrials.gov Identifier: NCT05997056
• Other Study ID Numbers: NET-202
• First Posted: August 18, 2023
• Last Update Posted: August 21, 2023
• Last Verified: August 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Aadi Bioscience, Inc.:

FYARRO; nab-sirolimus; ABI-009; Neuroendocrine Tumors; NET; Pancreatic Neuroendocrine Tumor; Gastrointestinal Neuroendocrine Tumor; Pulmonary Neuroendocrine Tumor

Additional relevant MeSH terms:

Neuroendocrine Tumors; Neoplasms; Adenoma, Islet Cell; Intestinal Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Adenoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Stomach Diseases; Sirolimus; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Antifungal Agents; Immunosuppressive Agents; Immunologic Factors