Savolitinib vs. Sunitinib in MET-driven PRCC.

• Sponsor: AstraZeneca (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03091192
• Collaborator: Hutchinson MediPharma (HMP) (Other)
• Enrollment: 60
• Locations: 58
• Arms: 2
• Anticipated Duration (Months): 65.2
• Patients Per Site: 1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study is designed for patients diagnosed with MET-driven, unresectable and locally advanced or metastatic Papillary Renal Cell Carcinoma. The purpose of this study is to see if an investigational new anti-cancer medication, savolitinib, is effective in treating patients with MET-driven PRCC, how it compares with another medication frequently used to treat this disease called sunitinib, and what side effects it might cause.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma; Carcinoma, Renal Cell; Kidney Neoplasms; Urologic Neoplasms; Kidney Diseases; Neoplasms by Site; Enzyme Inhibitors; Protein Kinase Inhibitors	Drug: Savolitinib; Drug: Sunitinib	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III, Open Label, Randomised, Controlled, Multi-Centre Study To Assess the Efficacy and Safety of Savolitinib Versus Sunitinib in Patients With MET-Driven, Unresectable and Locally Advanced, Or Metastatic Papillary Renal Cell Carcinoma (PRCC)
• Actual Study Start Date: Jul 25, 2017
• Actual Primary Completion Date: Aug 18, 2019
• Anticipated Study Completion Date: Dec 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Savolitinib See: intervention description	Drug: Savolitinib; 600 mg (400 mg if <50 kg) by mouth (PO) with a meal once daily (QD), continuously; Other Names: AZD6094 (HMPL-504)/Volitinib
Active Comparator: Sunitinib See: intervention description	Drug: Sunitinib; 50 mg by mouth (PO) once daily (QD), with or w/o food, 4 weeks on/2weeks off

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) [RECIST tumour assessments every 6 weeks from randomisation until disease progression as defined by Recist 1.1 and confirmed by BICR.]

   Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Progressive Disease (PD): >= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. PFS is the time from date of randomisation until the date of PD (defined by Recist 1.1 and confirmed by BICR) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression.

Secondary Outcome Measures

1. Overall Survival (OS) [RECIST tumour assessments every 6 weeks from randomisation until disease progression as defined by Recist 1.1 and confirmed by BICR.]

   Time between the date of randomisation and the date of death due to any cause.

2. Objective Response Rate (ORR) by BICR [RECIST tumour assessments every 6 weeks from randomisation until disease progression as defined by Recist 1.1 and confirmed by BICR.]

   Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. ORR is the percentage of patients with at least 1 visit response of CR or PR prior to progression or any further therapy.

3. Duration of Response (DoR) by BICR [RECIST tumour assessments every 6 weeks from randomisation until disease progression as defined by Recist 1.1 and confirmed by BICR.]

   Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. DoR is the time from the date of first documented response until the date of documented progression or death in the absence of disease progression.

4. Disease Control Rate (DCR) at 6 Months by BICR [RECIST tumour assessments every 6 weeks from randomisation until disease progression as defined by Recist 1.1 and confirmed by BICR.]

   Disease control rate at 6 months is defined as the percentage of patients who have a best objective response of Complete Response or Partial Response in that period or who have demonstrated Stable Disease for a minimum interval of 23 weeks.

5. Disease Control Rate (DCR) at 12 Months by BICR [RECIST tumour assessments every 6 weeks from randomisation until disease progression as defined by Recist 1.1 and confirmed by BICR.]

   Disease control rate at 12 months is defined as the percentage of patients who have a best objective response of complete responses or partial responses in that period or who have demonstrated stable disease for a minimum interval of 47 weeks.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 130 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Histologically confirmed PRCC, which is unresectable/locally advanced or metastatic with measurable disease as per RECIST 1.1. Patients with papillary urothelial carcinoma or renal pelvis cancer of the kidney are not considered PRCC and are not eligible.

2. Confirmation of MET-driven PRCC without co-occurring FH or VHL mutations from an FFPE tumour sample using the sponsor-designated central laboratory validated NGS assay

3. Patients who have received no prior systemic therapy as well as those who have received prior systemic therapy for PRCC in the advanced setting.* Patients can be treatment-naïve, or previously treated, but cannot have previously received sunitinib or a MET inhibitor. Patients who have received prior systemic therapy must have had disease progression in soft tissue disease or bone within 6 months of the last dose of the most recent systemic therapy

4. Adequate haematological, renal, cardiac and liver functions

5. Karnofsky performance status ≥ 80

Exclusion Criteria:

1. Most recent cytotoxic chemotherapy, immunotherapy, chemo-immunotherapy, or investigational agents <28 days from the date of randomisation. Most recent non cytotoxic targeted therapy <14 days from the date of randomisation.

2. Prior treatment with a MET inhibitor (e.g. foretinib, crizotinib, cabozantinib, onartuzumab or previous savolitinib) or sunitinb.

3. Treatment with strong inducers or inhibitors of CYP3A4 or strong inhibitors of CYP1A2, taken within 2 weeks or not possible to be stopped for at least 2 week before the date of randomisation. Herbal medications cannot be taken within 7 days of the date of randomisation (3 weeks for St John's wort).

4. Wide field radiotherapy administered ≤28 days or limited field radiation for palliation ≤7 days prior to the date of randomisation

5. Major surgical procedures ≤28 days of randomisation or minor surgical procedures ≤7 days. No waiting is required following port-a-cath placement.

6. Previously untreated brain metastases

7. Serious active infection or gastrointestinal disease

8. Presence of other active cancers, or history of treatment for invasive cancer within the last 5 years.

9. Mean resting QTcF >470 msec for women and >450 msec for men on the Part 2 screening triplicate ECGs or factors that may increase the risk of QTcF prolongation such as chronic hypokalaemia not correctable with supplements, congenital or familial long QT syndrome, or family history of unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	La Jolla	California	United States	92093
2	Research Site	Atlanta	Georgia	United States	30322
3	Research Site	Chicago	Illinois	United States	60637
4	Research Site	Iowa City	Iowa	United States	52242
5	Research Site	Boston	Massachusetts	United States	02215
6	Research Site	Kansas City	Missouri	United States	64132
7	Research Site	New York	New York	United States	10021
8	Research Site	Nashville	Tennessee	United States	37203
9	Research Site	Barretos		Brazil	14784-400
10	Research Site	Curitiba		Brazil	81520-060
11	Research Site	Passo Fundo		Brazil	99010-080
12	Research Site	Pelotas		Brazil	096015-280
13	Research Site	Porto Alegre		Brazil	90050-170
14	Research Site	Porto Alegre		Brazil	90610-000
15	Research Site	Porto Alegre		Brazil	91350-200
16	Research Site	Rio de Janeiro		Brazil	22793-080
17	Research Site	Sao Paulo		Brazil	01246-000
18	Research Site	Sao Paulo		Brazil	01323-903
19	Research Site	São José do Rio Preto		Brazil	15090-000
20	Research Site	Bordeaux		France	33000
21	Research Site	Vandoeuvre les Nancy		France	54519
22	Research Site	Villejuif		France	94805
23	Research Site	Arezzo		Italy	52100
24	Research Site	Meldola		Italy	47014
25	Research Site	Milano		Italy	20133
26	Research Site	Modena		Italy	41100
27	Research Site	Orbassano		Italy	10043
28	Research Site	Pavia		Italy	27100
29	Research Site	Roma		Italy	00152
30	Research Site	Daejeon		Korea, Republic of	35015
31	Research Site	Goyang-si		Korea, Republic of	10408
32	Research Site	Hwasun-gun		Korea, Republic of	58128
33	Research Site	Incheon		Korea, Republic of	21565
34	Research Site	Seoul		Korea, Republic of	03080
35	Research Site	Seoul		Korea, Republic of	05538
36	Research Site	Seoul		Korea, Republic of	06273
37	Research Site	Seoul		Korea, Republic of	120-752
38	Research Site	Seoul		Korea, Republic of	135-710
39	Research Site	Krasnoyarsk		Russian Federation	660133
40	Research Site	Moscow		Russian Federation	105077
41	Research Site	Moscow		Russian Federation	115478
42	Research Site	Moscow		Russian Federation	115522
43	Research Site	Moscow		Russian Federation	RU-121356
44	Research Site	Murmansk		Russian Federation	183047
45	Research Site	Nizhnii Novgorod		Russian Federation	603109
46	Research Site	Obninsk		Russian Federation	249036
47	Research Site	Omsk		Russian Federation	644013
48	Research Site	Saint Petersburg		Russian Federation	195271
49	Research Site	St. Petersburg		Russian Federation	194017
50	Research Site	Volgograd		Russian Federation	400138
51	Research Site	Dnipro		Ukraine	49005
52	Research Site	Dnipro		Ukraine	49102
53	Research Site	Ivano-Frankivsk		Ukraine	76018
54	Research Site	Kharkiv Region		Ukraine	61070
55	Research Site	Kyiv		Ukraine	03022
56	Research Site	Kyiv		Ukraine	03115
57	Research Site	Odesa		Ukraine	65055
58	Research Site	Sumy		Ukraine	40022

Sponsors and Collaborators

• AstraZeneca
• Hutchinson MediPharma (HMP)

Investigators

• Principal Investigator: Toni K Choueiri, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

• Study Protocol - Dec 19, 2018
• Statistical Analysis Plan - Aug 28, 2019

More Information

Additional Information:

• Related Info
• Related Info

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT03091192
• Other Study ID Numbers: D5082C00003
• First Posted: Mar 27, 2017
• Last Update Posted: Aug 18, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by AstraZeneca: Papillary Renal Cell Cancer; AZD6094; Savolitinib
• Additional relevant MeSH terms: Carcinoma; Neoplasms; Carcinoma, Renal Cell; Neoplasms by Site; Kidney Neoplasms; Urologic Neoplasms; Kidney Diseases; Sunitinib

Study Results

Participant Flow

Recruitment Details	First subject enrolled: 25 July 2017. Last subject last visit: 18 August 2019. Data cut off: 19 August 2019. The study was terminated prematurely. Randomized subjects continue to receive IMP as clinically indicated by PI; safety information is being collected for those subjects.

Arm/Group Title	Savolitinib QD	Sunitinib QD
Arm/Group Description	Savolitinib QD	Sunitinib QD
Period Title: Overall Study
STARTED	33	27
COMPLETED	0	0
NOT COMPLETED	33	27

Baseline Characteristics

Arm/Group Title	Savolitinib QD	Sunitinib QD	Total
Arm/Group Description	Savolitinib QD	Sunitinib QD	Total of all reporting groups
Overall Participants	33	27	60
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56.7 (13.81)	63.1 (9.60)	59.6 (12.43)
Sex: Female, Male (Count of Participants)
Female	4 12.1%	10 37%	14 23.3%
Male	29 87.9%	17 63%	46 76.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 6.1%	3 11.1%	5 8.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 3%	1 3.7%	2 3.3%
White	29 87.9%	23 85.2%	52 86.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 3%	0 0%	1 1.7%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS) by Blinded Independent Central Review (BICR)
Description	Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Progressive Disease (PD): >= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. PFS is the time from date of randomisation until the date of PD (defined by Recist 1.1 and confirmed by BICR) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression.
Time Frame	RECIST tumour assessments every 6 weeks from randomisation until disease progression as defined by Recist 1.1 and confirmed by BICR.

Outcome Measure Data

Analysis Population Description

Full Analysis Set (All randomised patients)

Arm/Group Title	Savolitinib QD	Sunitinib QD
Arm/Group Description	Savolitinib QD	Sunitinib QD
Measure Participants	33	27
Measure Events	17	20
Median (95% Confidence Interval) [Months]	7.0	5.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Savolitinib QD, Sunitinib QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.313
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 95%; 0.37 to 1.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Overall Survival (OS)
Description	Time between the date of randomisation and the date of death due to any cause.
Time Frame	RECIST tumour assessments every 6 weeks from randomisation until disease progression as defined by Recist 1.1 and confirmed by BICR.

Outcome Measure Data

Analysis Population Description

Full Analysis Set (All randomised patients)

Arm/Group Title	Savolitinib QD	Sunitinib QD
Arm/Group Description	Savolitinib QD	Sunitinib QD
Measure Participants	33	27
Died	9 27.3%	13 48.1%
Terminated study prior to death	24 72.7%	14 51.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Savolitinib QD, Sunitinib QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.110
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.51
	Confidence Interval	(2-Sided) 95%; 0.21 to 1.17
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1 favours Savolitinib

3. Secondary Outcome

Title	Objective Response Rate (ORR) by BICR
Description	Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. ORR is the percentage of patients with at least 1 visit response of CR or PR prior to progression or any further therapy.
Time Frame	RECIST tumour assessments every 6 weeks from randomisation until disease progression as defined by Recist 1.1 and confirmed by BICR.

Outcome Measure Data

Analysis Population Description

Full Analysis Set (All randomised patients)

Arm/Group Title	Savolitinib QD	Sunitinib QD
Arm/Group Description	Savolitinib QD	Sunitinib QD
Measure Participants	33	27
Number (95% Confidence Interval) [% of participants]	27.3 82.7%	7.4 27.4%

4. Secondary Outcome

Title	Duration of Response (DoR) by BICR
Description	Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. DoR is the time from the date of first documented response until the date of documented progression or death in the absence of disease progression.
Time Frame	RECIST tumour assessments every 6 weeks from randomisation until disease progression as defined by Recist 1.1 and confirmed by BICR.

Outcome Measure Data

Analysis Population Description

Duration of Response (DoR) by BICR was calculated for all responders (N=11)

Arm/Group Title	Savolitinib QD	Sunitinib QD
Arm/Group Description	Savolitinib QD	Sunitinib QD
Measure Participants	9	2
Median (95% Confidence Interval) [Months]	NA	8.3

5. Secondary Outcome

Title	Disease Control Rate (DCR) at 6 Months by BICR
Description	Disease control rate at 6 months is defined as the percentage of patients who have a best objective response of Complete Response or Partial Response in that period or who have demonstrated Stable Disease for a minimum interval of 23 weeks.
Time Frame	RECIST tumour assessments every 6 weeks from randomisation until disease progression as defined by Recist 1.1 and confirmed by BICR.

Outcome Measure Data

Analysis Population Description

Full Analysis Set (All randomised patients)

Arm/Group Title	Savolitinib QD	Sunitinib QD
Arm/Group Description	Savolitinib QD	Sunitinib QD
Measure Participants	33	27
Number (95% Confidence Interval) [% of participants]	48.5 147%	37.0 137%

6. Secondary Outcome

Title	Disease Control Rate (DCR) at 12 Months by BICR
Description	Disease control rate at 12 months is defined as the percentage of patients who have a best objective response of complete responses or partial responses in that period or who have demonstrated stable disease for a minimum interval of 47 weeks.
Time Frame	RECIST tumour assessments every 6 weeks from randomisation until disease progression as defined by Recist 1.1 and confirmed by BICR.

Outcome Measure Data

Analysis Population Description

Full Analysis Set (All randomised patients)

Arm/Group Title	Savolitinib QD	Sunitinib QD
Arm/Group Description	Savolitinib QD	Sunitinib QD
Measure Participants	33	27
Number (95% Confidence Interval) [% of participants]	30.3 91.8%	22.2 82.2%

Adverse Events

Time Frame	Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected throughout the study, from date of informed consent until 30 days after the last dose of study treatment.
Adverse Event Reporting Description	Systematic assessment due to regular investigator assessment at study visits.
Arm/Group Title	Savolitinib QD		Sunitinib QD
Arm/Group Description	Savolitinib QD		Sunitinib QD
All Cause Mortality
	Savolitinib QD		Sunitinib QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/33 (27.3%)		13/27 (48.1%)
Serious Adverse Events
	Savolitinib QD		Sunitinib QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/33 (24.2%)		8/27 (29.6%)
Blood and lymphatic system disorders
Thrombocytopenia	0/33 (0%)	0	1/27 (3.7%)	1
Cardiac disorders
Atrial fibrillation	0/33 (0%)	0	1/27 (3.7%)	1
Cardiac failure	0/33 (0%)	0	1/27 (3.7%)	1
Myocardial infarction	0/33 (0%)	0	1/27 (3.7%)	1
Ventricular tachycardia	1/33 (3%)	1	0/27 (0%)	0
Gastrointestinal disorders
Anal fistula	0/33 (0%)	0	1/27 (3.7%)	1
Ascites	1/33 (3%)	1	0/27 (0%)	0
Incarcerated umbilical hernia	1/33 (3%)	1	0/27 (0%)	0
Intestinal obstruction	1/33 (3%)	1	0/27 (0%)	0
General disorders
Condition aggravated	0/33 (0%)	0	1/27 (3.7%)	1
Oedema peripheral	1/33 (3%)	1	0/27 (0%)	0
Hepatobiliary disorders
Biliary dilatation	1/33 (3%)	1	0/27 (0%)	0
Cholangitis	1/33 (3%)	1	0/27 (0%)	0
Jaundice	1/33 (3%)	1	0/27 (0%)	0
Immune system disorders
Drug hypersensitivity	1/33 (3%)	1	0/27 (0%)	0
Infections and infestations
Pneumonia	1/33 (3%)	1	1/27 (3.7%)	1
Investigations
Alanine aminotransferase increased	1/33 (3%)	1	0/27 (0%)	0
Aspartate aminotransferase increased	1/33 (3%)	1	0/27 (0%)	0
Nervous system disorders
Thrombotic cerebral infarction	1/33 (3%)	1	0/27 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/33 (3%)	1	0/27 (0%)	0
Pleural effusion	1/33 (3%)	1	0/27 (0%)	0
Pulmonary embolism	0/33 (0%)	0	1/27 (3.7%)	1
Vascular disorders
Hypertensive urgency	0/33 (0%)	0	1/27 (3.7%)	1
Thrombophlebitis	1/33 (3%)	1	0/27 (0%)	0
Other (Not Including Serious) Adverse Events
	Savolitinib QD		Sunitinib QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/33 (75.8%)		27/27 (100%)
Blood and lymphatic system disorders
Anaemia	2/33 (6.1%)	2	12/27 (44.4%)	18
Leukopenia	1/33 (3%)	1	2/27 (7.4%)	3
Neutropenia	0/33 (0%)	0	5/27 (18.5%)	11
Thrombocytopenia	0/33 (0%)	0	6/27 (22.2%)	8
Cardiac disorders
Tachycardia	2/33 (6.1%)	2	1/27 (3.7%)	1
Gastrointestinal disorders
Abdominal pain upper	0/33 (0%)	0	4/27 (14.8%)	4
Constipation	2/33 (6.1%)	2	2/27 (7.4%)	2
Diarrhoea	0/33 (0%)	0	6/27 (22.2%)	19
Dyspepsia	1/33 (3%)	2	3/27 (11.1%)	3
Nausea	2/33 (6.1%)	3	9/27 (33.3%)	13
Odynophagia	0/33 (0%)	0	2/27 (7.4%)	2
Stomatitis	1/33 (3%)	1	2/27 (7.4%)	2
Vomiting	1/33 (3%)	1	4/27 (14.8%)	6
General disorders
Asthenia	1/33 (3%)	1	5/27 (18.5%)	5
Face oedema	0/33 (0%)	0	3/27 (11.1%)	3
Fatigue	2/33 (6.1%)	2	5/27 (18.5%)	5
Mucosal inflammation	0/33 (0%)	0	3/27 (11.1%)	4
Oedema peripheral	11/33 (33.3%)	17	3/27 (11.1%)	4
Peripheral swelling	2/33 (6.1%)	2	0/27 (0%)	0
Pyrexia	2/33 (6.1%)	2	2/27 (7.4%)	2
Infections and infestations
Conjuntivitis	0/33 (0%)	0	2/27 (7.4%)	2
Urinary tract infection	0/33 (0%)	0	4/27 (14.8%)	4
Investigations
Alanine aminotransferase increased	7/33 (21.2%)	11	3/27 (11.1%)	5
Amylase increased	1/33 (3%)	1	2/27 (7.4%)	2
Aspartate aminotransferase increased	7/33 (21.2%)	9	5/27 (18.5%)	7
Blood creatinine increased	9/33 (27.3%)	10	2/27 (7.4%)	2
Blood thyroid stimulating hormone decreased	0/33 (0%)	0	3/27 (11.1%)	3
Blood thyroid stimulating hormone increased	0/33 (0%)	0	4/27 (14.8%)	7
Body temperature increased	3/33 (9.1%)	3	2/27 (7.4%)	2
Ejection fraction decreased	0/33 (0%)	0	3/27 (11.1%)	3
Lipase increased	0/33 (0%)	0	2/27 (7.4%)	2
Neutrophil count decreased	0/33 (0%)	0	5/27 (18.5%)	11
Platelet count decreased	1/33 (3%)	2	4/27 (14.8%)	5
Thyroxine increased	0/33 (0%)	0	2/27 (7.4%)	2
Weight decreased	0/33 (0%)	0	2/27 (7.4%)	2
White blood cell count decreased	1/33 (3%)	1	3/27 (11.1%)	5
Metabolism and nutrition disorders
Decreased appetite	1/33 (3%)	1	8/27 (29.6%)	10
Dyslipidaemia	0/33 (0%)	0	2/27 (7.4%)	2
Hyperglycaemia	2/33 (6.1%)	2	0/27 (0%)	0
Hypoalbuminaemia	3/33 (9.1%)	3	2/27 (7.4%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	1/33 (3%)	1	2/27 (7.4%)	2
Back pain	2/33 (6.1%)	3	2/27 (7.4%)	4
Bone pain	0/33 (0%)	0	5/27 (18.5%)	5
Myalgia	0/33 (0%)	0	2/27 (7.4%)	2
Pain in extremity	2/33 (6.1%)	2	3/27 (11.1%)	4
Nervous system disorders
Dysgeusia	0/33 (0%)	0	2/27 (7.4%)	2
Headache	3/33 (9.1%)	3	4/27 (14.8%)	4
Taste disorder	0/33 (0%)	0	2/27 (7.4%)	3
Renal and urinary disorders
Chronic kidney disease	2/33 (6.1%)	2	1/27 (3.7%)	1
Proteinuria	1/33 (3%)	1	2/27 (7.4%)	2
Respiratory, thoracic and mediastinal disorders
Cough	4/33 (12.1%)	5	6/27 (22.2%)	6
Dyspnoea	7/33 (21.2%)	7	4/27 (14.8%)	4
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome	0/33 (0%)	0	7/27 (25.9%)	7
Pruritus	1/33 (3%)	1	2/27 (7.4%)	2
Rash	2/33 (6.1%)	3	1/27 (3.7%)	1
Yellow skin	0/33 (0%)	0	4/27 (14.8%)	4
Vascular disorders
Capillary leak syndrome	3/33 (9.1%)	3	0/27 (0%)	0
Hypertension	1/33 (3%)	1	6/27 (22.2%)	9

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.