Sintilimab Combined With IBI310 and Surufatinib for the Treatment of G3-NET and NEC (NESSIE)

NCT05165407 | Recruiting Phase 2

• 1 other identifier: CGOG-3006/2021-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase II, single arm, open-label, multicenter study to evaluate the efficacy and safety of Sintilimab combined with IBI310 and Surufatinib for the treatment of high-grade advanced-neuroendocrine neoplasm

Conditions

Neuroendocrine Neoplasm

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR, RECIST 1.1)

  The incidence of confirmed complete response or partial response

  From date of first dose of study drug until disease progression, withdrawal of consent, death, new anticancer therapy(up to approximately 2 years)

Secondary Outcomes (6)

• Objective response rate (ORR, iRECIST 1.1)

  From date of first dose of study drug until disease progression, withdrawal of consent, death, new anticancer therapy(up to approximately 2 years)

• Progression-free Survival (PFS)

  From date of first dose of study drug until disease progression, withdrawal of consent, death, new anticancer therapy (up to approximately 2 years)

• Duration of response (DoR)

  From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy (up to approximately 2 years)

• Overall survival (OS)

  From date of first dose of study drug until death caused by any reason (up to approximately 2 years)

• Safety of regimen as measured by incidence of adverse events

  The safety and tolerability of Surufatinib will be evaluated based on adverse events data. Other safety parameters include physical examination, vital signs, laboratory test results

Study Arms (1)

Sintilimab Combined With IBI310 and Surufatinib

EXPERIMENTAL

Surufatinib at a dose of 250mg QD, with Sintilimab injected intravenously 200mg per 3 weeks and IBI310 injected intravenously 1mg/kg per 6 weeks until disease progresses or unacceptable tolerability occurs

Drug: Sintilimab; Drug: IBI310; Drug: Surufatinib

Interventions

Sintilimab DRUG

Sintilimab 200mg will be intravenously administered on Day 1 of each cycle

Sintilimab Combined With IBI310 and Surufatinib

IBI310 DRUG

IBI310 1mg/kg be intravenously administered on Day 1 of every 2 cycle

Sintilimab Combined With IBI310 and Surufatinib

Surufatinib DRUG

Surufatinib 250mg will be taken orally once daily continuously

Also known as: HMPL-012

Sintilimab Combined With IBI310 and Surufatinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who included in this study must fulfil all of the following criteria:
• Fully aware of this study and voluntary to sign the informed consent form (the informed consent form must be signed before any trial-specific procedure is performed);
• Aged 18-75 (inclusive);
• Histologically or cytologically confirmed patients with inoperable or metastatic high-grade neuroendocrine neoplasm (Ki67 index \> 20% or with mitotic count of more than 20 mitoses per high power field);
• Patients who failed to receive standard treatment (Have progressed on previous treatment, or treatment toxicity and side effects are not tolerated), or cannot receive standard treatment (including patients who are intolerant to standard treatment, who are judged by the investigator to be unsuitable for standard treatment or who refuse to receive standard treatment), or who have no standard treatment plan;
• Having clear measurable lesions (according to RECIST 1.1). If the lesion is the only one that has received previous local treatment (radiotherapy, ablation, vascular intervention, etc.), there must be clear imaging evidence of disease progression in that lesion;
• Agree to provide tumor specimens (for further diagnosis of pathological grade, detection of PD-L1 expression and lymphocyte infiltration);
• ECOG performance status of 0 or 1;
• Brain metastases are asymptomatic or stable after local treatment are allowed to be enrolled as long as they meet the following conditions:
• \) Measurable lesions are outside of the central nervous system 2) No central nervous system symptoms or no exacerbation of symptoms for at least 2 weeks 3) No glucocorticoid treatment or discontinuation of glucocorticoid treatment within 7 days before first dose of study treatment.
• \. Patients were allowed to receive palliative radiation therapy, but it ended 14 days before the first dose of study treatment, and the radiation-related toxicity returned to grade 1 or less (CTCAE5.0); 10. Predicted survival ≥ 3 months; 11. Patients with adequate organ functions whose laboratory tests within 7 days before the first dose meet the following requirements:
• Absolute neutrophil count (ANC) ≥1.5x109/L within 14 days, without use of granulocyte colony-stimulating factor or other hematopoietic stimulating factor.
• Platelet count ≥100×109/L within 14 days, without blood transfusion or use of blood product.
• Hemoglobin ≥ 9 g/dL within 14 days, without blood transfusion or erythropoietin.
• Total bilirubin ≤1.5 × upper limit of normal (ULN); Such as total bilirubin \> 1.5×ULN, but direct bilirubin ≤ ULN was also allowed.

You may not qualify if:

• Subjects must be excluded from this study when any one of the following criteria is met:
• Presence of other malignancies in the past 5 years (except for basal cell carcinoma or squamous cell carcinoma of the skin and carcinoma in situ of the cervix, which were effectively controlled);
• Currently participate in an interventional clinical study, or have been treated with another study drug or medical equipment within 4 weeks prior to the first dose;
• Previous use of anti (PD-1), anti-PD-L1, anti-PD-L2 or CTLA-4 antibody or any other antibody acting on T cell co-stimulatory or checkpoint pathways (including but not limited to OX-40, CD137, etc.), anti-VEGF/VEGFR-targeted drugs;
• Having abnormal thyroid function with symptoms ongoing or requiring treatment at screening (only hypothyroidism that can be controlled by thyroid hormone replacement therapy can be included);
• Received systemic therapy with anti-neuroendocrine tumor of proprietary Chinese medicines or immunomodulatory drugs (including thymosin, interferon and interleukin, except for local control of pleural effusion) within 2 weeks prior to the first dose;
• Patients with any active autoimmune disorders requiring systematic treatment (e.g., palliative drugs, glucocorticoids, or immunosuppressants) or a history of autoimmune disease in the past 2 years. Alternative therapies (e.g. thyroxine, insulin, or physiologic glucocorticoids for adrenal or pituitary dysfunction) are not considered systemic;
• Use of immunosuppressant within 7 days prior to the first dose, not including local glucocorticoid via nasal spray, inhalation or other routes or systemic glucocorticoid at physiological dose. Note: Physiological doses of glucocorticoids (≤10 mg/ day of prednisone or equivalent dose) are permitted;
• Uncontrollable malignant hydrothorax, ascites or pericardial effusion (patients who do not need drainage effusion or who stop drainage for 3 days without significant increase in effusion can be included in the group);
• Use of CYP3A potent or moderate inducers during the administration of concomitant medications or within 1 weeks or 5 half-lives (whichever is longer) prior to the first dose (Appendix 3);
• Patients who currently have gastric and duodenal active ulcer, ulcerative colitis, or active bleeding in the unresected tumor, or serious gastrointestinal disorders, or other conditions that may cause haemorrhage of digestive tract or perforation;
• Patients with evidence or history of obvious bleeding tendency within 2 months prior to the first dose. (bleeding within 2 months \> 30 mL, hematemesis, black feces), hemoptysis (within 4 weeks \> 5 mL of fresh blood);
• Allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation;
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drugs (Sintilimab, IBI310, Surufatinib), or a prior history of severe allergy to any other monoclonal antibody.
• Patients with multiple factors affecting oral medication (such as inability to swallow, post-gastrointestinal resection, chronic diarrhea and intestinal obstruction);

Sponsors & Collaborators

• Peking University: lead

Study Sites (2)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

RECRUITING

Bejing cancer hospital

Beijing, Beijing Municipality, 100142, China

RECRUITING

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

sintilimab; surufatinib

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Central Study Contacts

Lin Shen

CONTACT

+86-10-88196561; linshenpku@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: December 7, 2021
• First Posted: December 21, 2021
• Study Start: July 12, 2022
• Primary Completion: September 1, 2025
• Study Completion: September 1, 2025
• Last Updated: March 14, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)