Trial Outcomes & Findings for Open-Label Surufatinib in European Patients With NET (NCT NCT04579679)

Last Updated: 2025-07-25

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

78 participants

Primary outcome timeframe

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

Results posted on

2025-07-25

Participant Flow

This Phase 2, multicenter, open-label study was conducted in patients with locally advanced or metastatic low to intermediate grade (Grade 1 or Grade 2), well-differentiated neuroendocrine tumors (NETs).

The study enrolled patients in 4 cohorts of varying NETs as follows: * Cohort A - NET of lung origin (NET, lung) * Cohort B - NET of small bowel origin (NET, small bowel) * Cohort C - NET of non-small bowel, non-pancreas, and non-lung origin (NET, other) * Cohort D - NET of any origin/drug-drug interaction sub-study (NET, any) The study was terminated early based on the strategic re-evaluation of the clinical development program for surufatinib and not due to any safety concerns.

Participant milestones

Participant milestones
Measure	Cohort A (NET, Lung) Patients with NET of lung origin received surufatinib 300 milligrams (mg) orally once daily (QD) in treatment cycles of 28 days starting on Cycle (C)1 Day (D)1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort B (NET, Small Bowel) Patients with NET of small bowel origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort C (NET, Other) Patients with NET of non-small bowel, non-pancreas, and non-lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort D (NET, Any) Patients with NET of any origin received a single dose of drug cocktail (midazolam 2.5 mg, fexofenadine 30 mg and rosuvastatin 10 mg) on Day -2 followed by surufatinib 300 mg orally QD from C1D1 to C1D14. On C1D15, a single dose of surufatinib 300 mg and a single dose of drug cocktail as above was administered. Patients received surufatinib 300 mg orally QD from C1D16 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.
Overall Study STARTED	20	32	20	6
Overall Study COMPLETED	0	1	0	2
Overall Study NOT COMPLETED	20	31	20	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort A (NET, Lung) Patients with NET of lung origin received surufatinib 300 milligrams (mg) orally once daily (QD) in treatment cycles of 28 days starting on Cycle (C)1 Day (D)1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort B (NET, Small Bowel) Patients with NET of small bowel origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort C (NET, Other) Patients with NET of non-small bowel, non-pancreas, and non-lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort D (NET, Any) Patients with NET of any origin received a single dose of drug cocktail (midazolam 2.5 mg, fexofenadine 30 mg and rosuvastatin 10 mg) on Day -2 followed by surufatinib 300 mg orally QD from C1D1 to C1D14. On C1D15, a single dose of surufatinib 300 mg and a single dose of drug cocktail as above was administered. Patients received surufatinib 300 mg orally QD from C1D16 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.
Overall Study New Antitumor Therapy	6	4	7	0
Overall Study Withdrawal of Consent	1	1	2	4
Overall Study Death	2	2	2	0
Overall Study Adverse Event	0	4	0	0
Overall Study Disease Progression	9	13	7	0
Overall Study Physician Decision	0	0	1	0
Overall Study Study Terminated by Sponsor	2	7	1	0

Baseline Characteristics

Open-Label Surufatinib in European Patients With NET

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A (NET, Lung) n=20 Participants Patients with NET of lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort B (NET, Small Bowel) n=32 Participants Patients with NET of small bowel origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort C (NET, Other) n=20 Participants Patients with NET of non-small bowel, non-pancreas, and non-lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort D (NET, Any) n=6 Participants Patients with NET of any origin received a single dose of drug cocktail (midazolam 2.5 mg, fexofenadine 30 mg and rosuvastatin 10 mg) on Day -2 followed by surufatinib 300 mg orally QD from C1D1 to C1D14. On C1D15, a single dose of surufatinib 300 mg and a single dose of drug cocktail as above was administered. Patients received surufatinib 300 mg orally QD from C1D16 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Total n=78 Participants Total of all reporting groups
Age, Continuous	63.5 years STANDARD_DEVIATION 12.77 • n=99 Participants	62.1 years STANDARD_DEVIATION 10.44 • n=107 Participants	57.3 years STANDARD_DEVIATION 15.52 • n=206 Participants	63.5 years STANDARD_DEVIATION 7.40 • n=7 Participants	61.3 years STANDARD_DEVIATION 12.37 • n=31 Participants
Sex: Female, Male Female	7 Participants n=99 Participants	20 Participants n=107 Participants	9 Participants n=206 Participants	4 Participants n=7 Participants	40 Participants n=31 Participants
Sex: Female, Male Male	13 Participants n=99 Participants	12 Participants n=107 Participants	11 Participants n=206 Participants	2 Participants n=7 Participants	38 Participants n=31 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants	3 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	3 Participants n=31 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants n=99 Participants	26 Participants n=107 Participants	13 Participants n=206 Participants	6 Participants n=7 Participants	60 Participants n=31 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=99 Participants	3 Participants n=107 Participants	7 Participants n=206 Participants	0 Participants n=7 Participants	15 Participants n=31 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	1 Participants n=31 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	3 Participants n=7 Participants	3 Participants n=31 Participants
Race/Ethnicity, Customized White	15 Participants n=99 Participants	28 Participants n=107 Participants	13 Participants n=206 Participants	3 Participants n=7 Participants	59 Participants n=31 Participants
Race/Ethnicity, Customized Not Reported	4 Participants n=99 Participants	1 Participants n=107 Participants	7 Participants n=206 Participants	0 Participants n=7 Participants	12 Participants n=31 Participants
Race/Ethnicity, Customized Other	0 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	1 Participants n=31 Participants
Race/Ethnicity, Customized Missing	1 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	2 Participants n=31 Participants

PRIMARY outcome

Timeframe: 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

Population: The efficacy analysis set included all patients who received at least 1 dose of surufatinib and had at least 1 post-baseline tumor assessment.

Outcome measures

Outcome measures
Measure	Cohort A (NET, Lung) n=20 Participants Patients with NET of lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort B (NET, Small Bowel) n=31 Participants Patients with NET of small bowel origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort C (NET, Other) n=19 Participants Patients with NET of non-small bowel, non-pancreas, and non-lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort D (NET, Any) n=5 Participants Patients with NET of any origin received a single dose of drug cocktail (midazolam 2.5 mg, fexofenadine 30 mg and rosuvastatin 10 mg) on Day -2 followed by surufatinib 300 mg orally QD from C1D1 to C1D14. On C1D15, a single dose of surufatinib 300 mg and a single dose of drug cocktail as above was administered. Patients received surufatinib 300 mg orally QD from C1D16 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.
Disease Control Rate (DCR)	95.0 percentage of participants Interval 75.1 to 99.9	90.3 percentage of participants Interval 74.2 to 98.0	89.5 percentage of participants Interval 66.9 to 98.7	100 percentage of participants Interval 47.8 to 100.0

SECONDARY outcome

Timeframe: 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

Population: The pharmacokinetic (PK) analysis set included all patients who received at least 1 dose of the study drug and had at least 1 measurable plasma concentration data point for at least 1 PK analyte without protocol violations or events with potential to affect the PK concentration. Only those participants with data collected at specified timepoints are reported.

Blood samples were collected at specified timepoints to obtain plasma concentrations of surufatinib at steady state on Cycle 1 Day 15.

Outcome measures

Outcome measures
Measure	Cohort A (NET, Lung) n=17 Participants Patients with NET of lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort B (NET, Small Bowel) n=29 Participants Patients with NET of small bowel origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort C (NET, Other) n=18 Participants Patients with NET of non-small bowel, non-pancreas, and non-lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort D (NET, Any) n=6 Participants Patients with NET of any origin received a single dose of drug cocktail (midazolam 2.5 mg, fexofenadine 30 mg and rosuvastatin 10 mg) on Day -2 followed by surufatinib 300 mg orally QD from C1D1 to C1D14. On C1D15, a single dose of surufatinib 300 mg and a single dose of drug cocktail as above was administered. Patients received surufatinib 300 mg orally QD from C1D16 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.
Plasma Concentrations of Surufatinib Pre-dose	73.123 nanogram/milliliter Geometric Coefficient of Variation 70.1	57.593 nanogram/milliliter Geometric Coefficient of Variation 136.8	49.258 nanogram/milliliter Geometric Coefficient of Variation 54.7	28.913 nanogram/milliliter Geometric Coefficient of Variation 130.5
Plasma Concentrations of Surufatinib 30 minutes post-dose	—	—	—	50.439 nanogram/milliliter Geometric Coefficient of Variation 190.5
Plasma Concentrations of Surufatinib 1 hour post-dose	130.456 nanogram/milliliter Geometric Coefficient of Variation 118.3	96.163 nanogram/milliliter Geometric Coefficient of Variation 115.2	101.464 nanogram/milliliter Geometric Coefficient of Variation 125.6	129.719 nanogram/milliliter Geometric Coefficient of Variation 303.6
Plasma Concentrations of Surufatinib 2 hours post-dose	234.498 nanogram/milliliter Geometric Coefficient of Variation 122.1	174.799 nanogram/milliliter Geometric Coefficient of Variation 138.1	194.654 nanogram/milliliter Geometric Coefficient of Variation 80.5	321.942 nanogram/milliliter Geometric Coefficient of Variation 99.9
Plasma Concentrations of Surufatinib 3 hours post-dose	287.237 nanogram/milliliter Geometric Coefficient of Variation 95.0	250.348 nanogram/milliliter Geometric Coefficient of Variation 101.8	245.379 nanogram/milliliter Geometric Coefficient of Variation 55.1	477.653 nanogram/milliliter Geometric Coefficient of Variation 118.6
Plasma Concentrations of Surufatinib 4 hours post-dose	293.236 nanogram/milliliter Geometric Coefficient of Variation 85.6	268.619 nanogram/milliliter Geometric Coefficient of Variation 65.9	232.657 nanogram/milliliter Geometric Coefficient of Variation 42.6	389.597 nanogram/milliliter Geometric Coefficient of Variation 102.8
Plasma Concentrations of Surufatinib 5 hours post-dose	—	—	—	357.045 nanogram/milliliter Geometric Coefficient of Variation 105.4
Plasma Concentrations of Surufatinib 6 hours post-dose	—	—	—	280.691 nanogram/milliliter Geometric Coefficient of Variation 105.2
Plasma Concentrations of Surufatinib 8 hours post-dose	—	—	—	202.345 nanogram/milliliter Geometric Coefficient of Variation 102.7
Plasma Concentrations of Surufatinib 10 hours post-dose	—	—	—	174.079 nanogram/milliliter Geometric Coefficient of Variation 84.1

SECONDARY outcome

Timeframe: From the first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 33 months

Population: The safety analysis set included all patients who received at least 1 dose of surufatinib. Only those patients with data collected are reported.

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.

Outcome measures

Outcome measures
Measure	Cohort A (NET, Lung) n=19 Participants Patients with NET of lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort B (NET, Small Bowel) n=31 Participants Patients with NET of small bowel origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort C (NET, Other) n=19 Participants Patients with NET of non-small bowel, non-pancreas, and non-lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort D (NET, Any) n=6 Participants Patients with NET of any origin received a single dose of drug cocktail (midazolam 2.5 mg, fexofenadine 30 mg and rosuvastatin 10 mg) on Day -2 followed by surufatinib 300 mg orally QD from C1D1 to C1D14. On C1D15, a single dose of surufatinib 300 mg and a single dose of drug cocktail as above was administered. Patients received surufatinib 300 mg orally QD from C1D16 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.
Number of Patients With Potentially Clinically Significant Corrected QT Interval (QTc) During Treatment QTcF: >450 msec to <=480 msec	0 Participants	2 Participants	0 Participants	2 Participants
Number of Patients With Potentially Clinically Significant Corrected QT Interval (QTc) During Treatment QTcF: >480 msec to <=500 msec	0 Participants	4 Participants	1 Participants	0 Participants
Number of Patients With Potentially Clinically Significant Corrected QT Interval (QTc) During Treatment QTcF: >500 msec	0 Participants	0 Participants	0 Participants	1 Participants
Number of Patients With Potentially Clinically Significant Corrected QT Interval (QTc) During Treatment QTcF: IFB >30 msec to <=60 msec	4 Participants	2 Participants	1 Participants	1 Participants
Number of Patients With Potentially Clinically Significant Corrected QT Interval (QTc) During Treatment QTcF: IFB >60 msec	0 Participants	2 Participants	0 Participants	1 Participants
Number of Patients With Potentially Clinically Significant Corrected QT Interval (QTc) During Treatment QTcB: >450 msec to <=480 msec	3 Participants	6 Participants	3 Participants	4 Participants
Number of Patients With Potentially Clinically Significant Corrected QT Interval (QTc) During Treatment QTcB: >480 msec to <=500 msec	0 Participants	1 Participants	0 Participants	1 Participants
Number of Patients With Potentially Clinically Significant Corrected QT Interval (QTc) During Treatment QTcB: >500 msec	0 Participants	1 Participants	1 Participants	1 Participants
Number of Patients With Potentially Clinically Significant Corrected QT Interval (QTc) During Treatment QTcB: IFB >30 msec to <=60 msec	2 Participants	7 Participants	4 Participants	1 Participants
Number of Patients With Potentially Clinically Significant Corrected QT Interval (QTc) During Treatment QTcB: IFB >60 msec	1 Participants	2 Participants	0 Participants	1 Participants

SECONDARY outcome

Population: The efficacy analysis set included all patients who received at least 1 dose of surufatinib and had at least 1 post-baseline tumor assessment.

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.

Outcome measures

Outcome measures
Measure	Cohort A (NET, Lung) n=20 Participants Patients with NET of lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort B (NET, Small Bowel) n=31 Participants Patients with NET of small bowel origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort C (NET, Other) n=19 Participants Patients with NET of non-small bowel, non-pancreas, and non-lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort D (NET, Any) n=5 Participants Patients with NET of any origin received a single dose of drug cocktail (midazolam 2.5 mg, fexofenadine 30 mg and rosuvastatin 10 mg) on Day -2 followed by surufatinib 300 mg orally QD from C1D1 to C1D14. On C1D15, a single dose of surufatinib 300 mg and a single dose of drug cocktail as above was administered. Patients received surufatinib 300 mg orally QD from C1D16 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.
Objective Response Rate (ORR)	15.0 percentage of participants Interval 3.2 to 37.9	16.1 percentage of participants Interval 5.5 to 33.7	5.3 percentage of participants Interval 0.1 to 26.0	20.0 percentage of participants Interval 0.5 to 71.6

SECONDARY outcome

Population: The efficacy analysis set included all patients who received at least 1 dose of surufatinib and had at least 1 post-baseline tumor assessment. Only those patients who achieved CR or PR (responders) were included in the analysis.

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.

Outcome measures

Outcome measures
Measure	Cohort A (NET, Lung) n=3 Participants Patients with NET of lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort B (NET, Small Bowel) n=5 Participants Patients with NET of small bowel origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort C (NET, Other) n=1 Participants Patients with NET of non-small bowel, non-pancreas, and non-lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort D (NET, Any) n=1 Participants Patients with NET of any origin received a single dose of drug cocktail (midazolam 2.5 mg, fexofenadine 30 mg and rosuvastatin 10 mg) on Day -2 followed by surufatinib 300 mg orally QD from C1D1 to C1D14. On C1D15, a single dose of surufatinib 300 mg and a single dose of drug cocktail as above was administered. Patients received surufatinib 300 mg orally QD from C1D16 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.
Time to Response (TTR)	2.1 months Interval 1.6 to 5.3	3.7 months Interval 1.8 to 14.2	11.1 months Interval 11.1 to 11.1	13.6 months Interval 13.6 to 13.6

SECONDARY outcome

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.

Outcome measures

Outcome measures
Measure	Cohort A (NET, Lung) n=3 Participants Patients with NET of lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort B (NET, Small Bowel) n=5 Participants Patients with NET of small bowel origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort C (NET, Other) n=1 Participants Patients with NET of non-small bowel, non-pancreas, and non-lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort D (NET, Any) n=1 Participants Patients with NET of any origin received a single dose of drug cocktail (midazolam 2.5 mg, fexofenadine 30 mg and rosuvastatin 10 mg) on Day -2 followed by surufatinib 300 mg orally QD from C1D1 to C1D14. On C1D15, a single dose of surufatinib 300 mg and a single dose of drug cocktail as above was administered. Patients received surufatinib 300 mg orally QD from C1D16 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.
Duration of Response (DOR)	16.9 months Interval 8.6 to NA indicates that upper limit of confidence interval (CI) was not estimable due to insufficient number of patients with events at study closure.	15.4 months Interval 3.7 to NA indicates that upper limit of CI was not estimable due to insufficient number of patients with events at study closure.	5.6 months NA indicates that upper and lower limits of CI could not be calculated for 1 patient.	NA months NA indicates that median, upper and lower limit of CI was not estimable due to insufficient number of patients with events at study closure.

SECONDARY outcome

Population: The safety analysis set included all patients who received at least 1 dose of surufatinib.

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.

Outcome measures

Outcome measures
Measure	Cohort A (NET, Lung) n=20 Participants Patients with NET of lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort B (NET, Small Bowel) n=32 Participants Patients with NET of small bowel origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort C (NET, Other) n=20 Participants Patients with NET of non-small bowel, non-pancreas, and non-lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort D (NET, Any) n=6 Participants Patients with NET of any origin received a single dose of drug cocktail (midazolam 2.5 mg, fexofenadine 30 mg and rosuvastatin 10 mg) on Day -2 followed by surufatinib 300 mg orally QD from C1D1 to C1D14. On C1D15, a single dose of surufatinib 300 mg and a single dose of drug cocktail as above was administered. Patients received surufatinib 300 mg orally QD from C1D16 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.
Progression-Free Survival (PFS)	10.2 months Interval 5.4 to 16.6	19.2 months Interval 8.3 to NA indicates that upper limit of CI was not estimable due to insufficient number of patients with events at study closure.	11.4 months Interval 5.7 to 16.7	9.8 months Interval 7.2 to NA indicates that upper limit of CI was not estimable due to insufficient number of patients with events at study closure.

SECONDARY outcome

Timeframe: Baseline (Day -2) and Cycle 1 Day 15

Population: The PK evaluable population included all patients who received at least 1 dose of the study drug and had sufficient concentration data to derive at least 1 PK parameter.

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.

Outcome measures

Outcome measures
Measure	Cohort A (NET, Lung) n=6 Participants Patients with NET of lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort B (NET, Small Bowel) Patients with NET of small bowel origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort C (NET, Other) Patients with NET of non-small bowel, non-pancreas, and non-lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort D (NET, Any) Patients with NET of any origin received a single dose of drug cocktail (midazolam 2.5 mg, fexofenadine 30 mg and rosuvastatin 10 mg) on Day -2 followed by surufatinib 300 mg orally QD from C1D1 to C1D14. On C1D15, a single dose of surufatinib 300 mg and a single dose of drug cocktail as above was administered. Patients received surufatinib 300 mg orally QD from C1D16 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.
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 Midazolam (CYP3A4 substrate), Cmax	1.69 Ratio of geometric LS mean Interval 1.2 to 2.39	—	—	—
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 Midazolam (CYP3A4 substrate), AUC0-t	1.70 Ratio of geometric LS mean Interval 1.14 to 2.52	—	—	—
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 Midazolam (CYP3A4 substrate), AUC0-inf	1.71 Ratio of geometric LS mean Interval 1.16 to 2.53	—	—	—
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 Fexofenadine (P-gp substrate), Cmax	2.03 Ratio of geometric LS mean Interval 1.51 to 2.75	—	—	—
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 Fexofenadine (P-gp substrate), AUC0-t	2.12 Ratio of geometric LS mean Interval 1.65 to 2.73	—	—	—
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 Fexofenadine (P-gp substrate), AUC0-inf	2.14 Ratio of geometric LS mean Interval 1.64 to 2.78	—	—	—
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 Rosuvastatin (BCRP substrate), Cmax	2.23 Ratio of geometric LS mean Interval 1.59 to 3.14	—	—	—
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 Rosuvastatin (BCRP substrate), AUC0-t	2.13 Ratio of geometric LS mean Interval 1.31 to 3.48	—	—	—
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 Rosuvastatin (BCRP substrate), AUC0-inf	2.23 Ratio of geometric LS mean Interval 1.23 to 4.01	—	—	—

SECONDARY outcome

Timeframe: From the first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 33 months

Population: The safety analysis set included all patients who received at least 1 dose of surufatinib.

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).

Outcome measures

Outcome measures
Measure	Cohort A (NET, Lung) n=20 Participants Patients with NET of lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort B (NET, Small Bowel) n=32 Participants Patients with NET of small bowel origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort C (NET, Other) n=20 Participants Patients with NET of non-small bowel, non-pancreas, and non-lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.	Cohort D (NET, Any) n=6 Participants Patients with NET of any origin received a single dose of drug cocktail (midazolam 2.5 mg, fexofenadine 30 mg and rosuvastatin 10 mg) on Day -2 followed by surufatinib 300 mg orally QD from C1D1 to C1D14. On C1D15, a single dose of surufatinib 300 mg and a single dose of drug cocktail as above was administered. Patients received surufatinib 300 mg orally QD from C1D16 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.
Number of Patients With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) TEAEs	20 Participants	32 Participants	20 Participants	6 Participants
Number of Patients With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) TESAEs	4 Participants	12 Participants	8 Participants	2 Participants

Adverse Events

Cohort A (NET, Lung)

Serious events: 4 serious events

Other events: 20 other events

Deaths: 2 deaths

Cohort B (NET, Small Bowel)

Serious events: 12 serious events

Other events: 32 other events

Deaths: 2 deaths

Cohort C (NET, Other)

Serious events: 8 serious events

Other events: 20 other events

Deaths: 2 deaths

Cohort D (NET, Any)

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Nick Lawn

HUTCHMED International Corporation

Phone: +44 7826 422448

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place