Open-Label Surufatinib in European Patients With NET

An Open-Label Phase 2 Study of Surufatinib in Patients With Neuroendocrine Tumours in Europe

This is a Phase 2, open-label, multi-centre study of surufatinib in patients with low to intermediate grade (Grade 1 or Grade 2), well-differentiated neuroendocrine tumours (NETs).

Study Overview

• Status: Terminated
• Conditions: Neuroendocrine Tumours; Neuroendocrine Tumour of the Lung; Small Intestinal NET
• Intervention / Treatment: Drug: Surufatinib

Detailed Description

This is a Phase 2, open-label, multi-centre study of surufatinib in patients with low- to intermediate-grade (Grade 1 or Grade 2), well-differentiated NETs.

The study will enroll 4 cohorts of varying NETs, as follows:

• Cohort A - NET of lung origin
• Cohort B - NET of small bowel origin
• Cohort C - NET of non-small bowel, non-pancreas, and non-lung origin
• Cohort D - NET of any origin (DDI substudy)

All patients will be treated with oral surufatinib 300 mg QD in treatment cycles of 28 days starting on Cycle 1 Day 1.

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Pessac, France, 33604
    • CHU Bordeaux
  • Villejuif, France, 94800
    • Institut Gustave Roussy
• Germany
  • Berlin, Germany, 13353
    • Charite Universitatsmedizin Berlin
  • Erlangen, Germany, 91054
    • Universitaetsklinikum Erlangen
  • Essen, Germany, 45147
    • Universitatsklinikum Essen, Klinik fur Endokrinologie
• Italy
  • Bari, Italy, 70124
    • Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari
  • Brescia, Italy, 25123
    • Asst-Spedali Civili di Brescia
  • Firenze, Italy, 50134
    • Universita degli Studi di Firenze - Azienda Ospedaliero Universitaria Careggi (AOUC)
  • Milano, Italy, 20141
    • Istituto Europeo di Oncologia
• Norway
  • Bergen, Norway, 5021
    • Haukeland University Hospital
  • Oslo, Norway, 0372
    • Oslo University Hospital Rikshospitalet
• Spain
  • Barcelona, Spain, 8035
    • Hospital Vall Hebron
  • Barcelona, Spain, 8013
    • Institut Catala d'Oncologis (ICO) - Hospital Duran i Reynals
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
• United Kingdom
  • London, United Kingdom, W1G 6AD
    • Sarah Cannon Research Institute
  • Manchester, United Kingdom, M20 4BX
    • Christie Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama, Birmingham (UAB)
  • California
    • Orange, California, United States, 92868
      • University of California Irvine Medical Center UCIMC - H.H. Chao Comprehensive Digestive Disease Center CDDC
  • Georgia
    • Atlanta, Georgia, United States, 30322-1013
      • Emory University, Winship Cancer Institute
  • New York
    • Stony Brook, New York, United States, 11794
      • Stony Brook Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. Has histologically or cytologically documented, locally advanced, or metastatic NET and has progressed on at least 1 prior line of therapy, but no more than 3 therapies;
2. Has radiologic evidence of progressive tumour within 12 months of study enrolment
3. Is willing and able to provide informed consent
4. Is ≥18 years of age
5. Has measurable lesions according to RECIST Version 1.1
6. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
7. Female patients of childbearing potential and male patients with partners of childbearing potential agree to use a highly effective form(s) of contraception

Key Exclusion Criteria:

1. Has an AE due to previous anti-tumour therapy that has not recovered to ≤CTCAE Grade 1, except alopecia and peripheral neurotoxicity with ≤CTCAE Grade 2 caused by platinum chemotherapy
2. Major surgery within previous 4 weeks or radiation therapy within 2 weeks prior to the start of treatment.
3. Prior VEGF/VEGFR-targeted therapy
4. Uncontrollable hypertension, defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, despite antihypertensive medication
5. Gastrointestinal disease or condition within 6 months prior to first dose
6. Has a history or presence of a serious haemorrhage (>30 mL within 3 months) or haemoptysis (>5 mL blood within 4 weeks) within 6 months of first dose of study drug.
7. Clinically significant cardiovascular disease.
8. Brain metastases and/or spinal cord compression untreated with surgery and/or radiotherapy, and without clinical imaging evidence of stable disease (SD) for 14 days or longer; patients requiring steroids within 4 weeks prior to start of study treatment will be excluded.
9. A high risk of bleeding at screening due to tumour invasion into major vessels, such as pulmonary artery, the superior vena cava, or the inferior vena cava, as determined by investigators.
10. Has arterial thrombosis or deep venous thrombosis within 6 months prior to first dosing, or thromboembolic events (including stroke and/or transient ischaemic attack) within 12 months.
11. Has a clinically meaningful ongoing infection (eg, requiring intravenous treatment with anti-infective therapy)

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: Surufatinib; Cohorts A, B, and C: oral surufatinib 300 mg once daily in treatment cycles of 28 days starting at Cycle 1 Day1 Cohort D: Surufatinib 300 mg once daily in treatment cycles of 28 days starting at Cycle 1 Day and single doses of drug cocktail on Day-2 and Day 15 Cycle 1	Drug: Surufatinib; Surufatinib 300 mg oral once daily; Other Names: HMPL-012, sulfatinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate (DCR)	The DCR was defined as the percentage of patients who achieved a best overall response (BOR) of complete response (CR), partial response (PR) or stable disease (SD) as determined by the Investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum on study.	RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentrations of Surufatinib	Blood samples were collected at specified timepoints to obtain plasma concentrations of surufatinib at steady state on Cycle 1 Day 15.	Cohorts A, B and C: Pre-dose and 1, 2, 3, 4 hours post-dose on Cycle 1 Day 15; Cohort D: Pre-dose and 30 minutes, 1, 2, 3, 4, 5, 6, 8 and 10 hours post-dose on Cycle 1 Day 15
Number of Patients With Potentially Clinically Significant Corrected QT Interval (QTc) During Treatment	The QT interval data was corrected for heart rate using 2 correction methods (Fridericia - QTcF and Bazett - QTcB). The treatment period was defined as the period from first administration of study drug up 30 days after last administration. msec=milliseconds, IFB=increase from baseline.	From the first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 33 months
Objective Response Rate (ORR)	The ORR was defined as the percentage of patients with a BOR of CR or PR as determined by the Investigator using RECIST v1.1. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.	RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months
Time to Response (TTR)	The TTR was defined as the time from the start of study drug until the date of first documented objective response, either CR or PR (whichever was recorded first) according to RECIST v.1.1 for responders only. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.	RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months
Duration of Response (DOR)	The DoR was defined as the time from the first time that the objective response reached CR or PR, whichever came first (and later confirmed), until the occurrence of PD or death. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters. The appearance of 1 or more new lesions was also considered progression.	RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months
Progression-Free Survival (PFS)	The PFS was defined as the time from the start of study drug until the first objective PD as defined by RECIST v1.1 or death, whichever came first. The PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters. The appearance of 1 or more new lesions was also considered progression.	RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months
Cohort D: Geometric Least Squares (LS) Mean Ratio of Cytochrome P450 (CYP3A4), P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) Substrates at Cycle 1 Day 15 to Baseline	Participants were administered midazolam, fexofenadine and rosuvastatin (as part of the drug cocktail) as a single dose on Day -2 (without surufatinib) and on Cycle 1 Day 15 (with surufatinib). Separate blood samples were collected for measurement of plasma concentrations of each probe substrate and surufatinib. Probe substrate of midazolam was CYP3A4, fexofenadine was P-gp and rosuvastatin was BCRP. Ratio of LS Mean for maximum plasma concentration (Cmax), area under the plasma concentration-time curve from time 0 to time of last measurable concentration (AUC0-t) and area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) are presented as Cycle 1 Day 15/Day -2.	Baseline (Day -2) and Cycle 1 Day 15
Number of Patients With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	An AE is any untoward medical occurrence in a clinical study patient temporally associated with the use of a study drug, whether or not considered related to the drug. An SAE was an AE that resulted in any of the following outcomes: death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; a congenital anomaly/birth defect or was any important medical event. TEAEs were defined as any AEs that started or worsened in severity on or after the first administration date of study drug and no later than 30 (+7) days after the last administration date of study drug or initiation of new anti-tumor therapy (whichever occurred first).	From the first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 33 months

Collaborators and Investigators

• Sponsor: Hutchmed
• Investigators: Study Director: William Schelman, MD, PhD, Hutchmed

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2021
• Primary Completion (Actual): September 6, 2024
• Study Completion (Actual): October 15, 2024

Study Registration Dates

• First Submitted: September 23, 2020
• First Submitted That Met QC Criteria: October 4, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Actual): July 25, 2025
• Last Update Submitted That Met QC Criteria: July 8, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: VEGF
• Additional Relevant MeSH Terms: Neoplasms by Site; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplasms; Lung Neoplasms; Neuroendocrine Tumors
• Other Study ID Numbers: 2020-012-00EU1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No