Sirolimus for Injection (Albumin Bound) Combined With Octreotide Long-acting Injection in Patients With Metastatic Gastroenteropancreatic Neuroendocrine Tumors

Phase II/III Study to Evaluate the Safety and Efficacy of Sirolimus for Injection (Albumin Bound) Combined With Octreotide Long-acting Injection in Patients With Metastatic Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)

There is limited evidence regarding the benefit of adding somatostatin analogs to molecular targeted agents for well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) with poor prognostic factors. This trial is conducted to evaluate sirolimus for injection (albumin bound) combined with octreotide long-acting injection in patients with unresectable or recurrent GEP-NETs.

Inclusion Criteria:

• 1. Unresectable locally advanced or metastatic G1/G2 GEP-NETs diagnosed by histology, according to the 2019 WHO histological grading criteria.
• 2. Having poor prognostic factors.
• 3. Non-functional GEP-NETs are required.
• 4. At least one evaluable lesion meets the RECIST V1.1 standard (Applicable only to the phase II safety run-in stage)
• 6. ECOG 0~2.
• 7. Organ function reserve is good.
• 8. Be able to sign a written informed consent form.

Exclusion Criteria:

• 1. Patients who have previously received SSTR-targeted therapies (including somatostatin analogs [SSAs] and peptide receptor radionuclide therapy) and/or mTOR inhibitors (Patients who received SSAs in the adjuvant setting and experienced recurrence ≥6 months after treatment completion may be enrolled)[ Applicable to Phase II dose expansion and Phase III stages].
• 2. Has uncontrolled/severe diarrhea or an axillary temperature > 38.0°C at enrollment.
• 3. Received treatment with other unlisted clinical investigational drugs within 4 weeks prior to the first use of the investigational drug.
• 4. Undergone major surgical procedures within 4 weeks prior to the first use of the investigational drug and have not fully recovered.
• 5. Received systemic use of corticosteroids or other immunosuppressive therapy within 2 weeks prior to the first use of the study drug.
• 6. With an infection that requires systemic anti-infective treatment within 2 weeks prior to the first use of the study drug.
• 7. Those who have used strong inhibitors or inducers of CYP3A4 liver metabolic enzymes within 2 weeks prior to the first use of the investigational drug or still need to continue using such drugs.
• 8. Has a serious history of cardiovascular and cerebrovascular diseases.
• 9. Having active brain metastasis and/or malignant meningitis.
• 10. With a history of severe lung diseases.
• 11. During screening, there may be symptomatic gallstones or a history of symptomatic gallstones but no surgical treatment has been performed.
• 12. Abnormal thyroid function during screening.
• 13. Known to have hypersensitivity reactions or intolerance to any component of all investigational drugs or their excipients.
• 14. Active hepatitis B, active hepatitis C virus infection, or active syphilis infection.
• 15. History of autoimmune diseases (excluding tuberous sclerosis), history of immunodeficiency, including HIV testing positive, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation.