A Study of AGS-16C3F vs. Axitinib in Metastatic Renal Cell Carcinoma

• Sponsor: Astellas Pharma Global Development, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02639182
• Collaborator: (none)
• Enrollment: 133
• Locations: 26
• Arms: 2
• Actual Duration (Months): 53
• Patients Per Site: 5.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study was to evaluate the progression free survival (PFS), based on investigator radiologic review, of AGS-16C3F compared to axitinib in subjects with metastatic renal cell carcinoma.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Renal Cell Carcinoma	Drug: AGS-16C3F; Drug: Axitinib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 133 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-Center, Open Label, Randomized Phase 2 Study of AGS-16C3F vs. Axitinib in Metastatic Renal Cell Carcinoma
• Actual Study Start Date: May 3, 2016
• Actual Primary Completion Date: Oct 2, 2020
• Actual Study Completion Date: Oct 2, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AGS-16C3F Participants received 1.8 milligram per kilogram (mg/kg) of AGS-16C3F once every three weeks by single intravenous (IV) infusion.	Drug: AGS-16C3F; Intravenous (IV) infusion
Active Comparator: Axitinib Participants received 2 to 10 milligram (mg) of axitinib twice daily by oral administration as defined in the product label and per local institutional guidelines.	Drug: Axitinib; Oral; Other Names: Inlyta®

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Investigator Radiologic Review [From date of randomization to the earliest of either documented disease progression or death from any cause (up to 53 months)]

   PFS was defined as the time from the date of randomization to the earliest of documented disease progression as defined by RECIST v.1.1 or death from any cause. PFS was analysed using Kaplan-Meier estimates. Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters (longest for non-nodal lesions, short axis for nodal lesions) of the target lesions taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The appearance of 1 or more new lesions is also considered progression. Participants were censored if there were 2 or more than 2 consecutive missing assesments immediately prior to death or progression; or no death and no postebaseline assesments; or if ininitiated non protocol anticancer treatment prior to death or prior to documentation of disease progression; or alive and not progressed.

Secondary Outcome Measures

1. PFS Per RECIST v1.1 as Assessed by Blinded Central Radiology Assessment [From date of randomization to the earliest of either documented disease progression or death from any cause (up to 40 months)]

   PFS was defined as the time from the date of randomization to the earliest of documented disease progression as defined by RECIST v.1.1 or death from any cause. PFS was analysed using Kaplan-Meier estimates. PD was defined as at least a 20% increase in the sum of diameters (longest for non-nodal lesions, short axis for nodal lesions) of the target lesions taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. The appearance of 1 or more new lesions is also considered progression. Participants were censored if there were 2 or more than 2 consecutive missing assessments immediately prior to death or progression; or no death and no postebaseline assessments; or if initiated non protocol anticancer treatment prior to death or prior to documentation of disease progression; or alive and not progressed.

2. Objective Response Rate (ORR) Based on the Investigator's Radiographic Assessment [From date of randomization until data cutoff date of 21 August 2019 (up to 40 months)]

   ORR was defined as the percentage of participants who had a best overall response of complete response (CR) or partial response (PR). CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) with reduction in short axis to <10mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters.

3. Duration of Response (DOR) Based on the Investigator's Radiographic Assessment [From date of first objective response until data cutoff date of 21 August 2019 (up to 40 months)]

   DOR was defined as the time from the date of the first response of CR or PR (whichever was first recorded) to the first date of documented PD or death due to any cause. DOR was analysed using Kaplan-Meier estimates. CR and PR were defined in outcome measure 3 and PD was defined in outcome measures 1 and 2. Participants were censored if there were 2 or more than 2 consecutive missing assesments immediately prior to death or progression; or no death and no postebaseline assesments; or if ininitiated non protocol anticancer treatment prior to death or prior to documentation of disease progression; or alive and not progressed.

4. Overall Survival (OS) [Date of randomization until the date of death from any cause (up to 53 months)]

   OS was defined as the time from the date of randomization until the date of death from any cause. OS was analysed using Kaplan-Meier estimates. Participants were censored if there was no death and no postbaseline contact or no death and at least one postbaseline follow-up.

5. Disease Control Rate (DCR) Based on the Investigator's Radiographic Assessment [Date of randomization until data cutoff date of 21 August 2019 (up to 40 months)]

   DCR was defined as the percentage of patients who had a best overall response of CR, PR or at least 6 months with stable disease (SD). CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) with reduction in short axis to <10mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters. SD was defined as neither sufficient decrease to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference the smallest sum of diameters while on study drug.

6. Number of Participants With Adverse Events [From first dose up to 53 months]

   AE was defined as any untoward medical occurrence in a participant administered a study drug or has undergone study procedures and which did not necessarily have a causal relationship with this treatment. An abnormality identified during a medical test (e.g., laboratory parameter, vital sign, ECG data, and physical exam) was defined as an AE only if the abnormality induces clinical signs or symptoms or requires active intervention or requires interruption or discontinuation of study medication or the abnormality or investigational value is clinically significant in the opinion of the investigator. AE was considered "serious" if it results in death or is life threatening results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions or results in congenital anomaly, or birth defect requires inpatient hospitalization or leads to prolongation of hospitalization or other medically important events.

7. Maximum Observed Serum Concentration (Cmax) of Antibody Drug Conjugate (ADC) [Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)]

   Cmax of ADC was reported.

8. Mean Predose Serum Concentration (Ctrough) of ADC [Predose on cycle 2, 3, 4, 6, 14, and 18 (each cycle is 21 days)]

   Ctrough of ADC was reported.

9. Time to Maximum Observed Serum Concentration (Tmax) of ADC [Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)]

   Tmax of ADC was reported.

10. Area Under the Concentration Versus Time Curve From Time Zero to 21days (AUC0 to 21) of ADC [Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)]

    AUC (0 to 21) of ADC was reported.

11. Terminal Elimination Half-life (t1/2) of ADC [Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)]

    t1/2 of ADC was reported.

12. Maximum Serum Concentration (Cmax) of Total Antibody (TAb) [Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)]

    Cmax of TAb was reported.

13. Mean Predose Serum Concnetration (Ctrough) of TAb [Predose on cycle 2, 3, 4, 6, 14, and 18 (each cycle is 21 days)]

    Ctrough of TAb was reported.

14. Time to Maximum Observed Serum Concentration (Tmax) of Tab [Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)]

    Tmax of TAb was reported.

15. Area Under the Concentration Versus Time Curve From Time Zero to 21days (AUC0 to 21) of TAb [Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)]

    AUC (0 to 21) of TAb was reporetd.

16. Terminal Elimination Half-life (t1/2) of Tab [Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)]

    t1/2 of TAb was reported.

17. Maximum Serum Concentration (Cmax) of Cysteine Adduct of Maleimidocaproyl Monomethyl Auristatin F (Cys-mcMMAF) [Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)]

    Cmax of Cys-mcMMAF was reported.

18. Mean Predose Serum Concnetration (Ctrough) of Cys-mcMMAF [Predose on cycle 2, 3, 4, 6, 14, and 18 (each cycle is 21 days)]

    Ctrough of Cys-mcMMAF was reported.

19. Time to Maximum Observed Serum Concentration (Tmax) of Cys-mcMMAF [Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)]

    Tmax of Cys-mcMMAF was reported.

20. Area Under the Concentration Versus Time Curve From Time Zero to 21days (AUC0 to 21) of Cys-mcMMAF [Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)]

    AUC (0 to 21) of Cys-mcMMAF was reporetd.

21. Terminal Elimination Half-life (t1/2) of Cys-mcMMAF [Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)]

    t1/2 of Cys-mcMMAF was reported

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed diagnosis of RCC

• Non-clear subjects must be ENPP3 positive, defined as IHC H-score ≥15

• Has evidence of progression on or after the last regimen received:

• Clear cell subject: must have received at least 2 prior systemic regimens, one of which is an anti-VEGF agent.

• Non-clear cell subject: must have received at least one prior anti-VEGF regimen

• Has measurable disease according to Response Criteria for Solid Tumors (RECIST v.1.1)

• Has Eastern Cooperative Group (ECOG) performance status of 0 or 1

• Has archive tumor tissue from primary tumor or metastatic site (excluding bone), for which the source and availability have been confirmed.

• If no archive tissue is available, the subject may elect to have a biopsy performed to obtain tissue.

• Has adequate organ function including:

• Hematopoietic function as follows:

1. Absolute neutrophil count (ANC) ≥ 1.5 x 10 9/L

2. Platelet count ≥ 100 x 10 9/L

3. Hemoglobin ≥ 9 g/dL (transfusions are allowed)

• Renal Function as follows:

1. Creatinine ≤ 1.5 x upper limit of normal (ULN), or calculated glomerular filtration rate (GFR) > 40 mL/min (Cockcroft-Gault) if creatinine > 1.5x ULN

• Hepatic function, as follows:

1. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 x ULN or ≤ 5x ULN if known liver metastases

2. Total bilirubin ≤ 1.5 x ULN

• Prothrombin time (PT) and activated partial thromboplastin time (aPTT) levels ≤1.5 x ULN. If institution does not report PT value, the international normalization ratio (INR) must be ≤ ULN.

• If subject is receiving Coumadin (warfarin), a stable international normalization ratio (INR) of 2-3 is required.

• No clinical symptoms of hypothyroidism

• Urine Protein to Creatinine Ratio (uPCR) < 2.0

• If uPCR ≥ 2.0 then a 24-hour urine collection can be performed to qualify. If this is performed to qualify, the protein result must be < 2 g per 24 hours.

• Female subject must either:

• Be of non-childbearing potential:

1. post-menopausal (defined as at least 1 year without any menses) prior to Screening, or

2. documented surgically sterile

• Or, if of childbearing potential,

1. Agree not to try to become pregnant during the study and for 6 months after the final study drug administration

2. And have a negative serum pregnancy test ≤ 10 days of cycle 1, day 1 (C1D1)

• And, if heterosexually active, agree to consistently use 2 forms of highly effective birth control* (at least one of which must be a barrier method) starting at Screening and throughout the study period and for 6 months after the final study drug administration.

• Female subject must agree not to breastfeed starting at Screening and throughout the study period, and for 6 months after the final study drug administration.

• Female subject must not donate ova starting at Screening and throughout the study period, and for 6 months after the final study drug administration.

• Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception* consisting of 2 forms of birth control (at least one of which must be a barrier method) starting at Screening and continue throughout the study period, and for 6 months after the final study drug administration

• Male subject must not donate sperm starting at Screening and throughout the study period and, for 6 months after the final study drug administration

Note: *Highly effective forms of birth control include:

• Consistent and correct usage of established oral contraception.

• Established intrauterine device (IUD) or intrauterine system (IUS).

• Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository

Exclusion Criteria:

• Has previously been treated with axitinib, AGS-16C3F, or AGS-16M8F

• Has untreated brain metastasis. In the case of a solitary brain metastasis which has been resected, there must be evidence of a disease-free interval of at least 3 months post-surgery. For brain metastases treated with whole brain or stereotactic radiation therapy, brain imaging must be stable > 3 months. All subjects previously treated for brain metastases must be stable off corticosteroid therapy for at least 28 days prior to C1D1.

• Has uncontrolled hypertension defined as blood pressure > 150/90 on medication(s) by 2 blood pressure readings taken at least 1 hour apart.

• Has gastrointestinal abnormalities including:

• inability to take oral medication;

• requirement for intravenous alimentation;

• prior surgical procedures affecting absorption including total gastric resection;

• active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy;

• malabsorption syndromes such as celiac disease, cystic fibrosis, inflammatory bowel disease, systemic sclerosis, and carcinoid syndrome

• Has ocular conditions such as:

• Active infection or corneal ulcer

• Monocularity

• Visual acuity of 20/70 or worse in both eyes

• History of corneal transplantation

• Contact lens dependent (if using contact lens, must be able to switch to glasses during the entire study duration)

• Uncontrolled glaucoma (topical medications allowed)

• Uncontrolled or active ocular problems (e.g., retinopathy, macular edema, active uveitis, wet macular degeneration) requiring surgery, laser treatment, or intravitreal injections

• Papilledema or other active optic nerve disorder

• Has used any investigational drug (including marketed drugs not approved for this indication) ≤ 14 days of C1D1. No time limit applies to the use of marketed drugs approved for this indication provided that the subject has progressed on the treatment and all toxicities attributable to the drug have resolved, returned to baseline or stabilized.

• Has known sensitivity to any of the ingredients of:

• investigational product AGS-16C3F and/or,

• Inlyta® (axitinib) and/or,

• 1% prednisolone acetate ophthalmic suspension and any other corticosteroids.

• Is currently using (i.e., within 14-days prior to first dose) drugs that are known strong CYP3A4/5 inhibitors / inducers.

• Thromboembolic event (e.g., deep vein thrombosis [DVT] and pulmonary embolism [PE]) ≤ 4 weeks of C1D1.

• Subjects who had a thromboembolic event ≤ 4 weeks of C1D1 must be receiving adequate anticoagulation treatment for at least 2 weeks before C1D1 and must continue as clinically indicated post first dose

• Has history bleeding disorders (e.g., pulmonary hemorrhage, significant hemoptysis, menometrorrhagia not responding to hormonal treatment) ≤ 2 months before C1D1

• Has active angina or Class III or IV Congestive Heart Failure (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 6 months of randomization, including myocardial infarction, unstable angina, Grade 2 or greater peripheral vascular disease, congestive heart failure, or arrhythmias not controlled by medication.

• Had major surgery ≤ 4 weeks of C1D1

• Is pregnant (confirmed by positive serum pregnancy test) or lactating

• Has active infection requiring treatment with systemic (intravenous or oral) anti-infectives (antibiotic, antifungal, or antiviral agent) ≤ 10 days of C1D1

• Is unwilling or unable to comply with study requirements

• Has any medical or psychiatric disorder that compromises the ability of the subject to give written informed consent, and/or comply with the study procedures.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site US01026	Tucson	Arizona	United States	85719
2	Site US01008	La Jolla	California	United States	92093
3	Site US01007	Los Angeles	California	United States	90033
4	Site US01020	Los Angeles	California	United States	90095
5	Site US01019	Palo Alto	California	United States	94305
6	Site US01010	Atlanta	Georgia	United States	30322
7	Site US01023	Baltimore	Maryland	United States	21201
8	Site US01002	Boston	Massachusetts	United States	02215
9	Site US01004	Ann Arbor	Michigan	United States	48109
10	Site US01013	Detroit	Michigan	United States	48202
11	Site US01012	Omaha	Nebraska	United States	68130
12	Site US01006	Buffalo	New York	United States	14263
13	Site US01022	Durham	North Carolina	United States	27710
14	Site US01017	Portland	Oregon	United States	97213
15	Site US01021	Pittsburgh	Pennsylvania	United States	15232
16	Site US01011	Charleston	South Carolina	United States	29425
17	Site US01003	Houston	Texas	United States	77030
18	Site US01014	Temple	Texas	United States	76508
19	Site US01001	Seattle	Washington	United States	98109
20	Site US01009	Milwaukee	Wisconsin	United States	53226
21	Site CA02006	Calgary	Alberta	Canada	T2N 4N2
22	Site CA02004	Edmonton	Alberta	Canada	T6G 1Z2
23	Site CA02005	Kelowna	British Columbia	Canada	V1Y 5L3
24	Site CA02001	Vancouver	British Columbia	Canada	V5Z 4E6
25	Site CA02002	Hamilton	Ontario	Canada	L8V 5C2
26	Site CA02008	London	Ontario	Canada	N6A 5W9

Sponsors and Collaborators

• Astellas Pharma Global Development, Inc.

Investigators

• Study Director: Associate Medical Director, Astellas Pharma Global Development, Inc.

Study Documents (Full-Text)

• Study Protocol - Aug 12, 2020
• Statistical Analysis Plan - Jun 10, 2019

More Information

Additional Information:

• Link to results and other applicable study documents on the Astellas Clinical Trials website
• Link to plain language summary of the study on the Trial Results Summaries website

Publications

None provided.

• Responsible Party: Astellas Pharma Global Development, Inc.
• ClinicalTrials.gov Identifier: NCT02639182
• Other Study ID Numbers: AGS-16C3F-15-3
• First Posted: Dec 24, 2015
• Last Update Posted: Nov 10, 2021
• Last Verified: Nov 1, 2021

• 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 Astellas Pharma Global Development, Inc.: Axitinib; Metastatic Renal Cell Carcinoma; AGS-16C3F
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Axitinib

Study Results

Participant Flow

Recruitment Details	Participants who were atleast 18 years of age with all histologies of confirmed renal cell carcinoma and evidence of progression on or after the last regimen received were enrolled.
Pre-assignment Detail	Randomization was stratified by Eastern Cooperative Oncology Group (ECOG) performance status (0 or 1), the number of prior systemic RCC regimens (2 or > 2) and Renal cell carcinoma (RCC), histology (clear or nonclear cell).

Arm/Group Title	AGS-16C3F	Axitinib
Arm/Group Description	Participants received 1.8 milligram per kilogram (mg/kg) of AGS-16C3F once every three weeks by single (60-minute) intravenous (IV) infusion.	Participants received axitinib at a starting dose of 5 milligram (mg) orally twice daily and then adjusted to 2 to 10 mg orally twice daily, as defined in the product label and per local institutional guidelines.
Period Title: Overall Study
STARTED	67	66
Treated	66	65
COMPLETED	0	0
NOT COMPLETED	67	66

Baseline Characteristics

Arm/Group Title	AGS-16C3F	Axitinib	Total
Arm/Group Description	Participants received 1.8 mg/kg of AGS-16C3F once every three weeks by single (60-minute) IV infusion.	Participants received axitinib at a starting dose of 5 mg orally twice daily and then adjusted to 2 to 10 mg orally twice daily, as defined in the product label and per local institutional guidelines.	Total of all reporting groups
Overall Participants	67	66	133
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	62.3 (9.1)	61.1 (8.9)	61.7 (9)
Sex: Female, Male (Count of Participants)
Female	18 26.9%	17 25.8%	35 26.3%
Male	49 73.1%	49 74.2%	98 73.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 4.5%	3 4.5%	6 4.5%
Not Hispanic or Latino	64 95.5%	62 93.9%	126 94.7%
Unknown or Not Reported	0 0%	1 1.5%	1 0.8%
Race/Ethnicity, Customized (Count of Participants)
White	59 88.1%	56 84.8%	115 86.5%
Asian	6 9%	7 10.6%	13 9.8%
American Indian or Alaska Native	1 1.5%	1 1.5%	2 1.5%
Other	1 1.5%	2 3%	3 2.3%
Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants)
0	19 28.4%	19 28.8%	38 28.6%
1	48 71.6%	47 71.2%	95 71.4%
Histological Type (Count of Participants)
Clear cell	55 82.1%	55 83.3%	110 82.7%
Non-clear cell	12 17.9%	11 16.7%	23 17.3%
Prognostic Risk Group (Count of Participants)
Favorable (0 risk factors)	5 7.5%	10 15.2%	15 11.3%
Intermediate (1-2 risk factors)	48 71.6%	43 65.2%	91 68.4%
Poor (>=3 risk factors)	14 20.9%	13 19.7%	27 20.3%
Number of Prior Systemic Renal cell carcinoma (RCC) Treatment Regimens (Count of Participants)
2 if clear cell or 1 if non-clear cell histology	35 52.2%	33 50%	68 51.1%
>2 if clear cell or >1 if non-clear cell histology	32 47.8%	33 50%	65 48.9%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Investigator Radiologic Review
Description	PFS was defined as the time from the date of randomization to the earliest of documented disease progression as defined by RECIST v.1.1 or death from any cause. PFS was analysed using Kaplan-Meier estimates. Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters (longest for non-nodal lesions, short axis for nodal lesions) of the target lesions taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The appearance of 1 or more new lesions is also considered progression. Participants were censored if there were 2 or more than 2 consecutive missing assesments immediately prior to death or progression; or no death and no postebaseline assesments; or if ininitiated non protocol anticancer treatment prior to death or prior to documentation of disease progression; or alive and not progressed.
Time Frame	From date of randomization to the earliest of either documented disease progression or death from any cause (up to 53 months)

Outcome Measure Data

Analysis Population Description

FAS Population

Arm/Group Title	AGS-16C3F	Axitinib
Arm/Group Description	Participants received 1.8 mg/kg of AGS-16C3F once every three weeks by single (60-minute) IV infusion.	Participants received axitinib at a starting dose of 5 mg orally twice daily and then adjusted to 2 to 10 mg orally twice daily, as defined in the product label and per local institutional guidelines.
Measure Participants	67	66
Median (95% Confidence Interval) [Months]	2.9	5.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AGS-16C3F, Axitinib
	Comments
	Type of Statistical Test	Superiority
	Comments	The difference between treatment groups was tested using a stratified log rank test at a one-sided 0.1 significance level.
Statistical Test of Hypothesis	p-Value	0.983
	Comments	The stratification factors were the ECOG PS at baseline and the number of prior systemic renal cell carcinoma (RCC) regimens, without any other covariate(s). The model contained terms for treatment group and stratum.
	Method	Log Rank
	Comments

2. Secondary Outcome

Title	PFS Per RECIST v1.1 as Assessed by Blinded Central Radiology Assessment
Description	PFS was defined as the time from the date of randomization to the earliest of documented disease progression as defined by RECIST v.1.1 or death from any cause. PFS was analysed using Kaplan-Meier estimates. PD was defined as at least a 20% increase in the sum of diameters (longest for non-nodal lesions, short axis for nodal lesions) of the target lesions taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. The appearance of 1 or more new lesions is also considered progression. Participants were censored if there were 2 or more than 2 consecutive missing assessments immediately prior to death or progression; or no death and no postebaseline assessments; or if initiated non protocol anticancer treatment prior to death or prior to documentation of disease progression; or alive and not progressed.
Time Frame	From date of randomization to the earliest of either documented disease progression or death from any cause (up to 40 months)

Outcome Measure Data

Analysis Population Description

FAS Population

Arm/Group Title	AGS-16C3F	Axitinib
Arm/Group Description	Participants received 1.8 mg/kg of AGS-16C3F once every three weeks by single (60-minute) IV infusion.	Participants received axitinib at a starting dose of 5 mg orally twice daily and then adjusted to 2 to 10 mg orally twice daily, as defined in the product label and per local institutional guidelines.
Measure Participants	67	66
Median (95% Confidence Interval) [Months]	3.5	4.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AGS-16C3F, Axitinib
	Comments
	Type of Statistical Test	Superiority
	Comments	The difference between treatment groups was tested using a stratified log rank test at a one-sided 0.1 significance level.
Statistical Test of Hypothesis	p-Value	0.110
	Comments	The stratification factors were the ECOG PS at baseline and the number of prior systemic RCC regimens, without any other covariate(s). The model contained terms for treatment group and stratum.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.423
	Confidence Interval	(2-Sided) 95%; 0.924 to 2.192
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Objective Response Rate (ORR) Based on the Investigator's Radiographic Assessment
Description	ORR was defined as the percentage of participants who had a best overall response of complete response (CR) or partial response (PR). CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) with reduction in short axis to <10mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters.
Time Frame	From date of randomization until data cutoff date of 21 August 2019 (up to 40 months)

Outcome Measure Data

Analysis Population Description

FAS Population

Arm/Group Title	AGS-16C3F	Axitinib
Arm/Group Description	Participants received 1.8 mg/kg of AGS-16C3F once every three weeks by single (60-minute) IV infusion.	Participants received axitinib at a starting dose of 5 mg orally twice daily and then adjusted to 2 to 10 mg orally twice daily, as defined in the product label and per local institutional guidelines.
Measure Participants	67	66
Number (95% Confidence Interval) [Percentage of Participants]	7.5 11.2%	18.2 27.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AGS-16C3F, Axitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.062
	Comments	A Cochran-Mantel-Haenszel (CMH) analysis of the ORR, stratified for baseline ECOG-PS and number of prior systemic therapies for RCC, was conducted at a two-sided significance level of 0.05.
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified Mantel-Haenszel estimate of the odds ratio for experiencing objective response, with the axitinib arm as the reference level, was reported.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; 0.1 to 1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Duration of Response (DOR) Based on the Investigator's Radiographic Assessment
Description	DOR was defined as the time from the date of the first response of CR or PR (whichever was first recorded) to the first date of documented PD or death due to any cause. DOR was analysed using Kaplan-Meier estimates. CR and PR were defined in outcome measure 3 and PD was defined in outcome measures 1 and 2. Participants were censored if there were 2 or more than 2 consecutive missing assesments immediately prior to death or progression; or no death and no postebaseline assesments; or if ininitiated non protocol anticancer treatment prior to death or prior to documentation of disease progression; or alive and not progressed.
Time Frame	From date of first objective response until data cutoff date of 21 August 2019 (up to 40 months)

Outcome Measure Data

Analysis Population Description

FAS Population

Arm/Group Title	AGS-16C3F	Axitinib
Arm/Group Description	Participants received 1.8 mg/kg of AGS-16C3F once every three weeks by single (60-minute) IV infusion.	Participants received axitinib at a starting dose of 5 mg orally twice daily and then adjusted to 2 to 10 mg orally twice daily, as defined in the product label and per local institutional guidelines.
Measure Participants	67	66
Median (95% Confidence Interval) [Months]	6.8	6.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AGS-16C3F, Axitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.439
	Comments	The stratification factors were the ECOG PS at baseline and the number of prior systemic RCC regimens, without any other covariate(s). The model contained terms for treatment group and stratum.
	Method	Log Rank
	Comments	The difference between treatment groups was tested using a stratified log rank test at a one-sided 0.1 significance level.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.376
	Confidence Interval	() 95%; 0.031 to 4.482
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from the date of randomization until the date of death from any cause. OS was analysed using Kaplan-Meier estimates. Participants were censored if there was no death and no postbaseline contact or no death and at least one postbaseline follow-up.
Time Frame	Date of randomization until the date of death from any cause (up to 53 months)

Outcome Measure Data

Analysis Population Description

FAS Population

Arm/Group Title	AGS-16C3F	Axitinib
Arm/Group Description	Participants received 1.8 mg/kg of AGS-16C3F once every three weeks by single (60-minute) IV infusion.	Participants received axitinib at a starting dose of 5 mg orally twice daily and then adjusted to 2 to 10 mg orally twice daily, as defined in the product label and per local institutional guidelines.
Measure Participants	67	66
Median (95% Confidence Interval) [Months]	13.1	15.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AGS-16C3F, Axitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.746
	Comments	Test conducted at a 2-sided significance level of 0.05. The stratification factors were the ECOG PS at baseline and number of prior systemic RCC regimens.
	Method	Log Rank
	Comments

6. Secondary Outcome

Title	Disease Control Rate (DCR) Based on the Investigator's Radiographic Assessment
Description	DCR was defined as the percentage of patients who had a best overall response of CR, PR or at least 6 months with stable disease (SD). CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) with reduction in short axis to <10mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters. SD was defined as neither sufficient decrease to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference the smallest sum of diameters while on study drug.
Time Frame	Date of randomization until data cutoff date of 21 August 2019 (up to 40 months)

Outcome Measure Data

Analysis Population Description

FAS Population

Arm/Group Title	AGS-16C3F	Axitinib
Arm/Group Description	Participants received 1.8 mg/kg of AGS-16C3F once every three weeks by single (60-minute) IV infusion.	Participants received axitinib at a starting dose of 5 mg orally twice daily and then adjusted to 2 to 10 mg orally twice daily, as defined in the product label and per local institutional guidelines.
Measure Participants	67	66
Number (95% Confidence Interval) [Percentage of Participants]	13.4 20%	22.7 34.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AGS-16C3F, Axitinib
	Comments
	Type of Statistical Test	Superiority
	Comments	A CMH analysis of the DCR, stratified for baseline ECOG-PS and number of prior systemic therapies for RCC, was conducted at a two-sided significance level of 0.05.
Statistical Test of Hypothesis	p-Value	0.152
	Comments	The stratified Mantel-Haenszel estimate of the odds ratio for experiencing objective response, with the axitinib arm as the reference level, was reported as a measure of relative treatment effect, along with its two-sided 95% CI.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 95%; 0.2 to 1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	AE was defined as any untoward medical occurrence in a participant administered a study drug or has undergone study procedures and which did not necessarily have a causal relationship with this treatment. An abnormality identified during a medical test (e.g., laboratory parameter, vital sign, ECG data, and physical exam) was defined as an AE only if the abnormality induces clinical signs or symptoms or requires active intervention or requires interruption or discontinuation of study medication or the abnormality or investigational value is clinically significant in the opinion of the investigator. AE was considered "serious" if it results in death or is life threatening results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions or results in congenital anomaly, or birth defect requires inpatient hospitalization or leads to prolongation of hospitalization or other medically important events.
Time Frame	From first dose up to 53 months

Outcome Measure Data

Analysis Population Description

Safety Population: All randomized participants who received at least one dose of study drug.

Arm/Group Title	AGS-16C3F	Axitinib
Arm/Group Description	Participants received 1.8 mg/kg of AGS-16C3F once every three weeks by single (60-minute) IV infusion.	Participants received axitinib at a starting dose of 5 mg orally twice daily and then adjusted to 2 to 10 mg orally twice daily, as defined in the product label and per local institutional guidelines.
Measure Participants	66	65
Number [Participants]	65 97%	64 97%

8. Secondary Outcome

Title	Maximum Observed Serum Concentration (Cmax) of Antibody Drug Conjugate (ADC)
Description	Cmax of ADC was reported.
Time Frame	Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population (PKAS): (included all participants who were randomized to receive AGS-16C3F and had sufficient serum concentration data to facilitate derivation of at least 1 pharmacokinetic parameter, and for whom the time of dosing on the day of sampling was known) with available data at specified time point.

Arm/Group Title	AGS-16C3F
Arm/Group Description	Participants received 1.8 mg/kg of AGS-16C3F once every three weeks by single (60-minute) IV infusion.
Measure Participants	59
Cycle 1	52.21 (58.407)
Cycle 4	48.66 (38.820)

9. Secondary Outcome

Title	Mean Predose Serum Concentration (Ctrough) of ADC
Description	Ctrough of ADC was reported.
Time Frame	Predose on cycle 2, 3, 4, 6, 14, and 18 (each cycle is 21 days)

Outcome Measure Data

Analysis Population Description

PKAS Population. Here, number of participants analyzed signifies participants who had quantifiable data.

Arm/Group Title	AGS-16C3F
Arm/Group Description	Participants received 1.8 mg/kg of AGS-16C3F once every three weeks by single (60-minute) IV infusion.
Measure Participants	50
Cycle 2	3429.39 (1402.334)
Cycle 3	5194.21 (3602.012)
Cycle 4	7731.38 (11171.906)
Cycle 6	5695.13 (3899.222)
Cycle 14	8698.26 (4239.327)
Cycle 18	7213.32 (2082.501)

10. Secondary Outcome

Title	Time to Maximum Observed Serum Concentration (Tmax) of ADC
Description	Tmax of ADC was reported.
Time Frame	Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)

Outcome Measure Data

Analysis Population Description

PKAS Population with available data at specified time point.

Arm/Group Title	AGS-16C3F
Arm/Group Description	Participants received 1.8 mg/kg of AGS-16C3F once every three weeks by single (60-minute) IV infusion.
Measure Participants	59
Cycle 1	0.04
Cycle 4	0.05

11. Secondary Outcome

Title	Area Under the Concentration Versus Time Curve From Time Zero to 21days (AUC0 to 21) of ADC
Description	AUC (0 to 21) of ADC was reported.
Time Frame	Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)

Outcome Measure Data

Analysis Population Description

PKAS Population with available data at specified time point.

Arm/Group Title	AGS-16C3F
Arm/Group Description	Participants received 1.8 mg/kg of AGS-16C3F once every three weeks by single (60-minute) IV infusion.
Measure Participants	52
Cycle 1	199.80 (68.821)
Cycle 4	293.90 (100.190)

12. Secondary Outcome

Title	Terminal Elimination Half-life (t1/2) of ADC
Description	t1/2 of ADC was reported.
Time Frame	Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)

Outcome Measure Data

Analysis Population Description

PKAS Population with available data at specified time point.

Arm/Group Title	AGS-16C3F
Arm/Group Description	Participants received 1.8 mg/kg of AGS-16C3F once every three weeks by single (60-minute) IV infusion.
Measure Participants	49
Cycle 1	6.93
Cycle 4	7.40

13. Secondary Outcome

Title	Maximum Serum Concentration (Cmax) of Total Antibody (TAb)
Description	Cmax of TAb was reported.
Time Frame	Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)

Outcome Measure Data

Analysis Population Description

PKAS Population with available data at specified time point.

Arm/Group Title	AGS-16C3F
Arm/Group Description	Participants received 1.8 mg/kg of AGS-16C3F once every three weeks by single (60-minute) IV infusion.
Measure Participants	59
Cycle 1	37.49 (12.515)
Cycle 4	42.84 (12.345)

14. Secondary Outcome

Title	Mean Predose Serum Concnetration (Ctrough) of TAb
Description	Ctrough of TAb was reported.
Time Frame	Predose on cycle 2, 3, 4, 6, 14, and 18 (each cycle is 21 days)

Outcome Measure Data

Analysis Population Description

PKAS Population. Here, number of participants analyzed signifies participants who had quantifiable data.

Arm/Group Title	AGS-16C3F
Arm/Group Description	Participants received 1.8 mg/kg of AGS-16C3F once every three weeks by single (60-minute) IV infusion.
Measure Participants	50
Cycle 2	4966.69 (2571.410)
Cycle 3	6943.11 (3666.956)
Cycle 4	8660.94 (4176.472)
Cycle 6	8777.51 (4131.388)
Cycle 14	12491.90 (6593.131)
Cycle 18	11726.15 (5572.172)

15. Secondary Outcome

Title	Time to Maximum Observed Serum Concentration (Tmax) of Tab
Description	Tmax of TAb was reported.
Time Frame	Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)

Outcome Measure Data

Analysis Population Description

PKAS Population with available data at specified time point.

Arm/Group Title	AGS-16C3F
Arm/Group Description	Participants received 1.8 mg/kg of AGS-16C3F once every three weeks by single (60-minute) IV infusion.
Measure Participants	60
Cycle 1	0.05
Cycle 4	0.05

16. Secondary Outcome

Title	Area Under the Concentration Versus Time Curve From Time Zero to 21days (AUC0 to 21) of TAb
Description	AUC (0 to 21) of TAb was reporetd.
Time Frame	Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)

Outcome Measure Data

Analysis Population Description

PKAS Population with available data at specified time point.

Arm/Group Title	AGS-16C3F
Arm/Group Description	Participants received 1.8 mg/kg of AGS-16C3F once every three weeks by single (60-minute) IV infusion.
Measure Participants	48
Cycle 1	246.06 (88.815)
Cycle 4	346.07 (158.029)

17. Secondary Outcome

Title	Terminal Elimination Half-life (t1/2) of Tab
Description	t1/2 of TAb was reported.
Time Frame	Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)

Outcome Measure Data

Analysis Population Description

PKAS Population with available data at specified time point.

Arm/Group Title	AGS-16C3F
Arm/Group Description	Participants received 1.8 mg/kg of AGS-16C3F once every three weeks by single (60-minute) IV infusion.
Measure Participants	45
Cycle 1	8.70
Cycle 4	9.15

18. Secondary Outcome

Title	Maximum Serum Concentration (Cmax) of Cysteine Adduct of Maleimidocaproyl Monomethyl Auristatin F (Cys-mcMMAF)
Description	Cmax of Cys-mcMMAF was reported.
Time Frame	Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)

Outcome Measure Data

Analysis Population Description

PKAS Population with available data at specified time point.

Arm/Group Title	AGS-16C3F
Arm/Group Description	Participants received 1.8 mg/kg of AGS-16C3F once every three weeks by single (60-minute) IV infusion.
Measure Participants	64
Cycle 1	6.09 (4.08)
Cycle 4	3.78 (1.70)

19. Secondary Outcome

Title	Mean Predose Serum Concnetration (Ctrough) of Cys-mcMMAF
Description	Ctrough of Cys-mcMMAF was reported.
Time Frame	Predose on cycle 2, 3, 4, 6, 14, and 18 (each cycle is 21 days)

Outcome Measure Data

Analysis Population Description

PKAS Population. Here, number of participants analyzed signifies participants who had quantifiable data.

Arm/Group Title	AGS-16C3F
Arm/Group Description	Participants received 1.8 mg/kg of AGS-16C3F once every three weeks by single (60-minute) IV infusion.
Measure Participants	1
Cycle 6	0.307 (NA)

20. Secondary Outcome

Title	Time to Maximum Observed Serum Concentration (Tmax) of Cys-mcMMAF
Description	Tmax of Cys-mcMMAF was reported.
Time Frame	Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)

Outcome Measure Data

Analysis Population Description

PKAS Population with available data at specified time point.

Arm/Group Title	AGS-16C3F
Arm/Group Description	Participants received 1.8 mg/kg of AGS-16C3F once every three weeks by single (60-minute) IV infusion.
Measure Participants	64
Cycle 1	0.207
Cycle 4	0.208

21. Secondary Outcome

Title	Area Under the Concentration Versus Time Curve From Time Zero to 21days (AUC0 to 21) of Cys-mcMMAF
Description	AUC (0 to 21) of Cys-mcMMAF was reporetd.
Time Frame	Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)

Outcome Measure Data

Analysis Population Description

PKAS Population with available data at specified time point. Not calculated at cycle 4 due to an insufficient number of participants.

Arm/Group Title	AGS-16C3F
Arm/Group Description	Participants received 1.8 mg/kg of AGS-16C3F once every three weeks by single (60-minute) IV infusion.
Measure Participants	21
Cycle 1	9.61 (10.3)

22. Secondary Outcome

Title	Terminal Elimination Half-life (t1/2) of Cys-mcMMAF
Description	t1/2 of Cys-mcMMAF was reported
Time Frame	Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)

Outcome Measure Data

Analysis Population Description

PKAS Population with available data at specified time point. Not calculated at cycle 4 due to an insufficient number of samples.

Arm/Group Title	AGS-16C3F
Arm/Group Description	Participants received 1.8 mg/kg of AGS-16C3F once every three weeks by single (60-minute) IV infusion.
Measure Participants	1
Cycle 1	2.72

Adverse Events

Time Frame	From first dose up to 53 months
Adverse Event Reporting Description	All-cause mortality data was reported for FAS population. Serious and non-serious adverse events were reported for safety population.
Arm/Group Title	AGS-16C3F		Axitinib
Arm/Group Description	Participants received 1.8 mg/kg of AGS-16C3F once every three weeks by single (60-minute) IV infusion.		Participants received axitinib at a starting dose of 5 mg orally twice daily and then adjusted to 2 to 10 mg orally twice daily, as defined in the product label and per local institutional guidelines.
All Cause Mortality
	AGS-16C3F		Axitinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/67 (53.7%)		44/66 (66.7%)
Serious Adverse Events
	AGS-16C3F		Axitinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/66 (39.4%)		31/65 (47.7%)
Blood and lymphatic system disorders
Anaemia	1/66 (1.5%)	1	0/65 (0%)	0
Iron deficiency anaemia	1/66 (1.5%)	1	0/65 (0%)	0
Thrombocytopenia	2/66 (3%)	2	0/65 (0%)	0
Cardiac disorders
Angina pectoris	1/66 (1.5%)	2	0/65 (0%)	0
Angina unstable	1/66 (1.5%)	1	0/65 (0%)	0
Aortic valve disease	1/66 (1.5%)	1	0/65 (0%)	0
Cardiac arrest	1/66 (1.5%)	1	1/65 (1.5%)	1
Cardiac tamponade	0/66 (0%)	0	1/65 (1.5%)	1
Cardio-respiratory arrest	0/66 (0%)	0	1/65 (1.5%)	1
Pericardial effusion	0/66 (0%)	0	1/65 (1.5%)	1
Sinus tachycardia	0/66 (0%)	0	1/65 (1.5%)	1
Endocrine disorders
Adrenal insufficiency	1/66 (1.5%)	1	0/65 (0%)	0
Gastrointestinal disorders
Abdominal hernia	0/66 (0%)	0	1/65 (1.5%)	1
Abdominal pain	3/66 (4.5%)	4	0/65 (0%)	0
Abdominal pain upper	0/66 (0%)	0	1/65 (1.5%)	1
Diarrhoea	1/66 (1.5%)	1	2/65 (3.1%)	2
Gastrointestinal haemorrhage	1/66 (1.5%)	2	0/65 (0%)	0
Inguinal hernia	0/66 (0%)	0	1/65 (1.5%)	1
Pancreatitis	0/66 (0%)	0	1/65 (1.5%)	1
Pneumoperitoneum	0/66 (0%)	0	1/65 (1.5%)	1
Small intestinal haemorrhage	1/66 (1.5%)	1	0/65 (0%)	0
Small intestinal obstruction	0/66 (0%)	0	1/65 (1.5%)	1
General disorders
Asthenia	0/66 (0%)	0	1/65 (1.5%)	1
Device failure	0/66 (0%)	0	1/65 (1.5%)	1
Fatigue	0/66 (0%)	0	1/65 (1.5%)	1
Influenza like illness	1/66 (1.5%)	1	0/65 (0%)	0
Non-cardiac chest pain	1/66 (1.5%)	1	0/65 (0%)	0
Pyrexia	1/66 (1.5%)	1	0/65 (0%)	0
Hepatobiliary disorders
Cholecystitis	0/66 (0%)	0	1/65 (1.5%)	1
Hepatic failure	1/66 (1.5%)	1	0/65 (0%)	0
Infections and infestations
Clostridium difficile infection	1/66 (1.5%)	1	0/65 (0%)	0
Osteomyelitis	0/66 (0%)	0	1/65 (1.5%)	1
Pneumonia	0/66 (0%)	0	2/65 (3.1%)	2
Sepsis	0/66 (0%)	0	1/65 (1.5%)	1
Sinusitis	0/66 (0%)	0	1/65 (1.5%)	1
Wound infection staphylococcal	0/66 (0%)	0	1/65 (1.5%)	1
Injury, poisoning and procedural complications
Fall	0/66 (0%)	0	1/65 (1.5%)	1
Hip fracture	0/66 (0%)	0	1/65 (1.5%)	1
Humerus fracture	1/66 (1.5%)	1	0/65 (0%)	0
Infusion related reaction	1/66 (1.5%)	1	0/65 (0%)	0
Post procedural haematoma	0/66 (0%)	0	1/65 (1.5%)	1
Investigations
Liver function test abnormal	1/66 (1.5%)	1	0/65 (0%)	0
Platelet count decreased	1/66 (1.5%)	1	0/65 (0%)	0
Transaminases increased	1/66 (1.5%)	1	0/65 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/66 (0%)	0	4/65 (6.2%)	4
Failure to thrive	1/66 (1.5%)	1	0/65 (0%)	0
Hypercalcaemia	0/66 (0%)	0	1/65 (1.5%)	1
Hyperglycaemia	1/66 (1.5%)	1	0/65 (0%)	0
Hyponatraemia	1/66 (1.5%)	1	0/65 (0%)	0
Malnutrition	0/66 (0%)	0	1/65 (1.5%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	2/66 (3%)	2	0/65 (0%)	0
Back pain	0/66 (0%)	0	2/65 (3.1%)	2
Bone pain	0/66 (0%)	0	1/65 (1.5%)	1
Cervical spinal stenosis	1/66 (1.5%)	1	0/65 (0%)	0
Groin pain	1/66 (1.5%)	1	0/65 (0%)	0
Haemarthrosis	0/66 (0%)	0	1/65 (1.5%)	1
Muscle haemorrhage	1/66 (1.5%)	1	0/65 (0%)	0
Pain in extremity	0/66 (0%)	0	2/65 (3.1%)	2
Pathological fracture	0/66 (0%)	0	1/65 (1.5%)	1
Soft tissue necrosis	0/66 (0%)	0	1/65 (1.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system	1/66 (1.5%)	1	0/65 (0%)	0
Metastatic pain	1/66 (1.5%)	1	0/65 (0%)	0
Prostate cancer	0/66 (0%)	0	1/65 (1.5%)	1
Nervous system disorders
Altered state of consciousness	1/66 (1.5%)	1	0/65 (0%)	0
Cauda equina syndrome	0/66 (0%)	0	1/65 (1.5%)	1
Encephalopathy	1/66 (1.5%)	1	1/65 (1.5%)	1
Haemorrhagic stroke	1/66 (1.5%)	1	0/65 (0%)	0
Hemiparesis	1/66 (1.5%)	1	0/65 (0%)	0
Lethargy	0/66 (0%)	0	1/65 (1.5%)	1
Loss of consciousness	1/66 (1.5%)	1	0/65 (0%)	0
Spinal cord compression	1/66 (1.5%)	2	0/65 (0%)	0
Psychiatric disorders
Confusional state	1/66 (1.5%)	1	2/65 (3.1%)	2
Renal and urinary disorders
Acute kidney injury	1/66 (1.5%)	1	2/65 (3.1%)	3
Haematuria	1/66 (1.5%)	1	1/65 (1.5%)	1
Reproductive system and breast disorders
Vaginal haemorrhage	0/66 (0%)	0	1/65 (1.5%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/66 (1.5%)	1	2/65 (3.1%)	2
Haemoptysis	0/66 (0%)	0	1/65 (1.5%)	1
Hypoxia	1/66 (1.5%)	1	0/65 (0%)	0
Pleural effusion	1/66 (1.5%)	1	1/65 (1.5%)	1
Pneumothorax	0/66 (0%)	0	2/65 (3.1%)	3
Pulmonary venous thrombosis	1/66 (1.5%)	1	0/65 (0%)	0
Tracheal stenosis	0/66 (0%)	0	1/65 (1.5%)	1
Surgical and medical procedures
Craniotomy	0/66 (0%)	0	1/65 (1.5%)	1
Vascular disorders
Deep vein thrombosis	0/66 (0%)	0	1/65 (1.5%)	2
Haematoma	1/66 (1.5%)	1	0/65 (0%)	0
Hypotension	0/66 (0%)	0	1/65 (1.5%)	1
Ischaemia	0/66 (0%)	0	1/65 (1.5%)	1
Peripheral ischaemia	0/66 (0%)	0	1/65 (1.5%)	1
Other (Not Including Serious) Adverse Events
	AGS-16C3F		Axitinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	65/66 (98.5%)		64/65 (98.5%)
Blood and lymphatic system disorders
Anaemia	15/66 (22.7%)	35	4/65 (6.2%)	7
Thrombocytopenia	5/66 (7.6%)	9	0/65 (0%)	0
Endocrine disorders
Hypothyroidism	1/66 (1.5%)	1	7/65 (10.8%)	8
Eye disorders
Diplopia	4/66 (6.1%)	4	0/65 (0%)	0
Dry eye	14/66 (21.2%)	18	6/65 (9.2%)	6
Eye pain	7/66 (10.6%)	7	0/65 (0%)	0
Photophobia	5/66 (7.6%)	5	0/65 (0%)	0
Vision blurred	26/66 (39.4%)	38	7/65 (10.8%)	8
Gastrointestinal disorders
Abdominal distension	4/66 (6.1%)	4	5/65 (7.7%)	5
Abdominal pain	12/66 (18.2%)	20	10/65 (15.4%)	12
Constipation	16/66 (24.2%)	16	21/65 (32.3%)	25
Diarrhoea	12/66 (18.2%)	18	31/65 (47.7%)	70
Dry mouth	6/66 (9.1%)	8	6/65 (9.2%)	10
Dyspepsia	4/66 (6.1%)	6	7/65 (10.8%)	10
Dysphagia	2/66 (3%)	2	5/65 (7.7%)	5
Gastrooesophageal reflux disease	1/66 (1.5%)	2	7/65 (10.8%)	8
Nausea	31/66 (47%)	56	26/65 (40%)	40
Oral pain	0/66 (0%)	0	5/65 (7.7%)	8
Stomatitis	2/66 (3%)	2	15/65 (23.1%)	23
Vomiting	18/66 (27.3%)	25	22/65 (33.8%)	38
General disorders
Asthenia	7/66 (10.6%)	8	5/65 (7.7%)	7
Chills	15/66 (22.7%)	29	2/65 (3.1%)	4
Fatigue	36/66 (54.5%)	48	37/65 (56.9%)	67
Influenza like illness	2/66 (3%)	2	5/65 (7.7%)	5
Mucosal inflammation	1/66 (1.5%)	1	5/65 (7.7%)	9
Non-cardiac chest pain	3/66 (4.5%)	3	4/65 (6.2%)	4
Oedema peripheral	11/66 (16.7%)	13	7/65 (10.8%)	10
Pain	1/66 (1.5%)	1	4/65 (6.2%)	4
Pyrexia	9/66 (13.6%)	18	1/65 (1.5%)	1
Infections and infestations
Pneumonia	1/66 (1.5%)	1	5/65 (7.7%)	5
Upper respiratory tract infection	4/66 (6.1%)	5	4/65 (6.2%)	4
Injury, poisoning and procedural complications
Contusion	5/66 (7.6%)	7	1/65 (1.5%)	1
Fall	5/66 (7.6%)	7	1/65 (1.5%)	1
Infusion related reaction	7/66 (10.6%)	16	0/65 (0%)	0
Investigations
Alanine aminotransferase increased	4/66 (6.1%)	4	3/65 (4.6%)	5
Aspartate aminotransferase increased	5/66 (7.6%)	8	5/65 (7.7%)	7
Blood bilirubin increased	4/66 (6.1%)	10	2/65 (3.1%)	3
Blood creatinine increased	5/66 (7.6%)	8	5/65 (7.7%)	10
Blood thyroid stimulating hormone increased	0/66 (0%)	0	5/65 (7.7%)	5
Platelet count decreased	5/66 (7.6%)	9	2/65 (3.1%)	2
Weight decreased	7/66 (10.6%)	13	19/65 (29.2%)	30
Metabolism and nutrition disorders
Decreased appetite	14/66 (21.2%)	17	24/65 (36.9%)	45
Dehydration	6/66 (9.1%)	7	11/65 (16.9%)	15
Hypercalcaemia	5/66 (7.6%)	6	3/65 (4.6%)	4
Hypomagnesaemia	2/66 (3%)	2	4/65 (6.2%)	5
Hyponatraemia	3/66 (4.5%)	6	5/65 (7.7%)	5
Hypophosphataemia	1/66 (1.5%)	1	4/65 (6.2%)	6
Musculoskeletal and connective tissue disorders
Arthralgia	10/66 (15.2%)	13	9/65 (13.8%)	12
Back pain	11/66 (16.7%)	23	24/65 (36.9%)	27
Flank pain	3/66 (4.5%)	3	7/65 (10.8%)	7
Groin pain	4/66 (6.1%)	4	2/65 (3.1%)	2
Muscular weakness	5/66 (7.6%)	5	10/65 (15.4%)	12
Musculoskeletal chest pain	6/66 (9.1%)	8	6/65 (9.2%)	7
Musculoskeletal pain	11/66 (16.7%)	13	11/65 (16.9%)	13
Neck pain	3/66 (4.5%)	3	7/65 (10.8%)	12
Pain in extremity	6/66 (9.1%)	8	14/65 (21.5%)	22
Nervous system disorders
Dizziness	14/66 (21.2%)	18	12/65 (18.5%)	16
Dysgeusia	3/66 (4.5%)	3	10/65 (15.4%)	11
Headache	16/66 (24.2%)	20	16/65 (24.6%)	23
Memory impairment	4/66 (6.1%)	4	0/65 (0%)	0
Paraesthesia	2/66 (3%)	3	4/65 (6.2%)	4
Peripheral sensory neuropathy	5/66 (7.6%)	6	2/65 (3.1%)	2
Tremor	4/66 (6.1%)	4	0/65 (0%)	0
Psychiatric disorders
Anxiety	4/66 (6.1%)	4	2/65 (3.1%)	2
Confusional state	4/66 (6.1%)	6	5/65 (7.7%)	7
Insomnia	6/66 (9.1%)	6	7/65 (10.8%)	7
Renal and urinary disorders
Pollakiuria	1/66 (1.5%)	1	4/65 (6.2%)	4
Proteinuria	1/66 (1.5%)	1	5/65 (7.7%)	10
Respiratory, thoracic and mediastinal disorders
Cough	17/66 (25.8%)	19	15/65 (23.1%)	20
Dysphonia	1/66 (1.5%)	1	25/65 (38.5%)	26
Dyspnoea	13/66 (19.7%)	19	18/65 (27.7%)	21
Epistaxis	14/66 (21.2%)	23	5/65 (7.7%)	7
Nasal congestion	1/66 (1.5%)	1	5/65 (7.7%)	7
Oropharyngeal pain	4/66 (6.1%)	4	6/65 (9.2%)	7
Pleural effusion	4/66 (6.1%)	8	7/65 (10.8%)	10
Skin and subcutaneous tissue disorders
Decubitus ulcer	1/66 (1.5%)	1	4/65 (6.2%)	4
Night sweats	5/66 (7.6%)	5	2/65 (3.1%)	2
Palmar-plantar erythrodysaesthesia syndrome	0/66 (0%)	0	14/65 (21.5%)	38
Pruritus	11/66 (16.7%)	12	3/65 (4.6%)	3
Rash	6/66 (9.1%)	7	4/65 (6.2%)	4
Rash maculo-papular	5/66 (7.6%)	6	3/65 (4.6%)	5
Vascular disorders
Hypertension	4/66 (6.1%)	10	27/65 (41.5%)	48
Hypotension	4/66 (6.1%)	6	6/65 (9.2%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.