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CompletedNCT02639182Updated Nov 18, 2024Results posted

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

A Phase 2 interventional study of AGS-16C3F and Axitinib in Metastatic Renal Cell Carcinoma, sponsored by Astellas Pharma Global Development, Inc.. Completed at 26 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-11-18.

Sponsored by Astellas Pharma Global Development, Inc. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
133
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Metastatic Renal Cell Carcinoma

Keywords

  • Axitinib
  • Metastatic Renal Cell Carcinoma
  • AGS-16C3F
03

In context

Carcinoma

6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.

This study's enrollment of 133 is above the median of 45 across 5,170 interventional studies indexed under Carcinoma.

Browse Carcinoma studies →

Lead sponsor

Astellas Pharma Global Development, Inc. is the lead sponsor of 204 studies on the registry; 25 are open to participants now.

Of its 80 completed or terminated interventional studies of FDA-regulated products, 38 (48%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
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

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.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
133 participants (actual)

Study arms

  • 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

  • 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

Interventions

  • DrugAGS-16C3F

    Intravenous (IV) infusion

  • DrugAxitinib

    Oral

    Also known as: Inlyta®

06

What researchers measure

Primary outcomes

  1. Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Investigator Radiologic Review

    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)

Secondary outcomes

  1. PFS Per RECIST v1.1 as Assessed by Blinded Central Radiology Assessment

    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)

  2. Objective Response Rate (ORR) Based on the Investigator's Radiographic Assessment

    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)

  3. Duration of Response (DOR) Based on the Investigator's Radiographic Assessment

    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)

  4. Overall Survival (OS)

    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)

  5. Disease Control Rate (DCR) Based on the Investigator's Radiographic Assessment

    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)

  6. Number of Participants With Adverse Events

    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

  7. Maximum Observed Serum Concentration (Cmax) of Antibody Drug Conjugate (ADC)

    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)

  8. Mean Predose Serum Concentration (Ctrough) of ADC

    Ctrough of ADC was reported.

    Time frame: Predose on cycle 2, 3, 4, 6, 14, and 18 (each cycle is 21 days)

  9. Time to Maximum Observed Serum Concentration (Tmax) of ADC

    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)

  10. Area Under the Concentration Versus Time Curve From Time Zero to 21days (AUC0 to 21) of ADC

    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)

  11. Terminal Elimination Half-life (t1/2) of ADC

    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)

  12. Maximum Serum Concentration (Cmax) of Total Antibody (TAb)

    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)

  13. Mean Predose Serum Concnetration (Ctrough) of TAb

    Ctrough of TAb was reported.

    Time frame: Predose on cycle 2, 3, 4, 6, 14, and 18 (each cycle is 21 days)

  14. Time to Maximum Observed Serum Concentration (Tmax) of Tab

    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)

  15. Area Under the Concentration Versus Time Curve From Time Zero to 21days (AUC0 to 21) of TAb

    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)

  16. Terminal Elimination Half-life (t1/2) of Tab

    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)

  17. Maximum Serum Concentration (Cmax) of Cysteine Adduct of Maleimidocaproyl Monomethyl Auristatin F (Cys-mcMMAF)

    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)

  18. Mean Predose Serum Concnetration (Ctrough) of Cys-mcMMAF

    Ctrough of Cys-mcMMAF was reported.

    Time frame: Predose on cycle 2, 3, 4, 6, 14, and 18 (each cycle is 21 days)

  19. Time to Maximum Observed Serum Concentration (Tmax) of Cys-mcMMAF

    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)

  20. Area Under the Concentration Versus Time Curve From Time Zero to 21days (AUC0 to 21) of Cys-mcMMAF

    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)

  21. Terminal Elimination Half-life (t1/2) of Cys-mcMMAF

    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)

07

Results

Posted Sep 23, 2020

Participant flow

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.

Participant flow — Overall Study
MilestoneAGS-16C3FAxitinib
Started6766
Treated6665
Completed00
Not completed6766
Withdrew: Disease progression5049
Withdrew: Adverse event75
Withdrew: Physician decision33
Withdrew: Withdrew consent54
Withdrew: Lost to follow-up01
Withdrew: Study closure12
Withdrew: Sponsor ended study01
Withdrew: Randomized but did not receive study drug11

Outcome measures

PrimaryProgression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Investigator Radiologic Review

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)
Reported as:
Median · Months
Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Investigator Radiologic Review
MonthsAGS-16C3FAxitinib
Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Investigator Radiologic Review2.9 (2.0 to 4.0)5.7 (5.3 to 9.1)
Statistical analysis
  • AGS-16C3F vs Axitinib · Log Rank · p = 0.983 (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.)
SecondaryPFS Per RECIST v1.1 as Assessed by Blinded Central Radiology Assessment

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)
Reported as:
Median · Months
PFS Per RECIST v1.1 as Assessed by Blinded Central Radiology Assessment
MonthsAGS-16C3FAxitinib
PFS Per RECIST v1.1 as Assessed by Blinded Central Radiology Assessment3.5 (2.1 to 3.8)4.5 (3.5 to 7.6)
Statistical analysis
  • AGS-16C3F vs Axitinib · Log Rank · p = 0.110 (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.) · Hazard ratio (hr): 1.423 · 95% CI 0.924 to 2.192
SecondaryObjective Response Rate (ORR) Based on the Investigator's Radiographic Assessment

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)
Reported as:
Number · Percentage of Participants
Objective Response Rate (ORR) Based on the Investigator's Radiographic Assessment
Percentage of ParticipantsAGS-16C3FAxitinib
Objective Response Rate (ORR) Based on the Investigator's Radiographic Assessment7.5 (2.5 to 16.6)18.2 (9.8 to 29.6)
Statistical analysis
  • AGS-16C3F vs Axitinib · Cochran-Mantel-Haenszel · p = 0.062 (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.) · Odds ratio (or): 0.4 · 95% CI 0.1 to 1.1Stratified Mantel-Haenszel estimate of the odds ratio for experiencing objective response, with the axitinib arm as the reference level, was reported.
SecondaryDuration of Response (DOR) Based on the Investigator's Radiographic Assessment

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)
Reported as:
Median · Months
Duration of Response (DOR) Based on the Investigator's Radiographic Assessment
MonthsAGS-16C3FAxitinib
Duration of Response (DOR) Based on the Investigator's Radiographic Assessment6.8 (3.8 to 18.4)6.7 (1.8 to 9.2)
Statistical analysis
  • AGS-16C3F vs Axitinib · Log Rank · p = 0.439 (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.) · Hazard ratio (hr): 0.376 · 95% CI 0.031 to 4.482The difference between treatment groups was tested using a stratified log rank test at a one-sided 0.1 significance level.
SecondaryOverall Survival (OS)

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)
Reported as:
Median · Months
Overall Survival (OS)
MonthsAGS-16C3FAxitinib
Overall Survival (OS)13.1 (10.1 to 23.0)15.5 (12.7 to 21.6)
Statistical analysis
  • AGS-16C3F vs Axitinib · Log Rank · p = 0.746 (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.)
SecondaryDisease Control Rate (DCR) Based on the Investigator's Radiographic Assessment

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)
Reported as:
Number · Percentage of Participants
Disease Control Rate (DCR) Based on the Investigator's Radiographic Assessment
Percentage of ParticipantsAGS-16C3FAxitinib
Disease Control Rate (DCR) Based on the Investigator's Radiographic Assessment13.4 (6.3 to 24.0)22.7 (13.3 to 34.7)
Statistical analysis
  • AGS-16C3F vs Axitinib · Cochran-Mantel-Haenszel · p = 0.152 (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.) · Odds ratio (or): 0.5 · 95% CI 0.2 to 1.3
SecondaryNumber of Participants With Adverse Events

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
Reported as:
Number · Participants
Number of Participants With Adverse Events
ParticipantsAGS-16C3FAxitinib
Number of Participants With Adverse Events6564
SecondaryMaximum Observed Serum Concentration (Cmax) of Antibody Drug Conjugate (ADC)

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)
Reported as:
Mean · Microgram per Milliliter (μg/mL)
Maximum Observed Serum Concentration (Cmax) of Antibody Drug Conjugate (ADC)
Microgram per Milliliter (μg/mL)AGS-16C3F
Cycle 152.21 ± 58.407
Cycle 448.66 ± 38.820
SecondaryMean Predose Serum Concentration (Ctrough) of ADC

Ctrough of ADC was reported.

Time frame:
Predose on cycle 2, 3, 4, 6, 14, and 18 (each cycle is 21 days)
Reported as:
Mean · Nanogram per Milliliter (ng/mL)
Mean Predose Serum Concentration (Ctrough) of ADC
Nanogram per Milliliter (ng/mL)AGS-16C3F
Cycle 23429.39 ± 1402.334
Cycle 35194.21 ± 3602.012
Cycle 47731.38 ± 11171.906
Cycle 65695.13 ± 3899.222
Cycle 148698.26 ± 4239.327
Cycle 187213.32 ± 2082.501
SecondaryTime to Maximum Observed Serum Concentration (Tmax) of ADC

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)
Reported as:
Median · Days
Time to Maximum Observed Serum Concentration (Tmax) of ADC
DaysAGS-16C3F
Cycle 10.04 (0.0 to 1.0)
Cycle 40.05 (0.0 to 3.9)
SecondaryArea Under the Concentration Versus Time Curve From Time Zero to 21days (AUC0 to 21) of ADC

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)
Reported as:
Mean · Day*Microgram per Milliliter (day*μg/mL)
Area Under the Concentration Versus Time Curve From Time Zero to 21days (AUC0 to 21) of ADC
Day*Microgram per Milliliter (day*μg/mL)AGS-16C3F
Cycle 1199.80 ± 68.821
Cycle 4293.90 ± 100.190
SecondaryTerminal Elimination Half-life (t1/2) of ADC

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)
Reported as:
Median · Days
Terminal Elimination Half-life (t1/2) of ADC
DaysAGS-16C3F
Cycle 16.93 (3.9 to 19.6)
Cycle 47.40 (3.6 to 14.5)
SecondaryMaximum Serum Concentration (Cmax) of Total Antibody (TAb)

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)
Reported as:
Mean · μg/mL
Maximum Serum Concentration (Cmax) of Total Antibody (TAb)
μg/mLAGS-16C3F
Cycle 137.49 ± 12.515
Cycle 442.84 ± 12.345
SecondaryMean Predose Serum Concnetration (Ctrough) of TAb

Ctrough of TAb was reported.

Time frame:
Predose on cycle 2, 3, 4, 6, 14, and 18 (each cycle is 21 days)
Reported as:
Mean · ng/mL
Mean Predose Serum Concnetration (Ctrough) of TAb
ng/mLAGS-16C3F
Cycle 24966.69 ± 2571.410
Cycle 36943.11 ± 3666.956
Cycle 48660.94 ± 4176.472
Cycle 68777.51 ± 4131.388
Cycle 1412491.90 ± 6593.131
Cycle 1811726.15 ± 5572.172
SecondaryTime to Maximum Observed Serum Concentration (Tmax) of Tab

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)
Reported as:
Median · Days
Time to Maximum Observed Serum Concentration (Tmax) of Tab
DaysAGS-16C3F
Cycle 10.05 (0.0 to 2.2)
Cycle 40.05 (0.0 to 3.9)
SecondaryArea Under the Concentration Versus Time Curve From Time Zero to 21days (AUC0 to 21) of TAb

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)
Reported as:
Mean · day*μg/mL
Area Under the Concentration Versus Time Curve From Time Zero to 21days (AUC0 to 21) of TAb
day*μg/mLAGS-16C3F
Cycle 1246.06 ± 88.815
Cycle 4346.07 ± 158.029
SecondaryTerminal Elimination Half-life (t1/2) of Tab

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)
Reported as:
Median · Days
Terminal Elimination Half-life (t1/2) of Tab
DaysAGS-16C3F
Cycle 18.70 (4.3 to 16.6)
Cycle 49.15 (1.8 to 38.1)
SecondaryMaximum Serum Concentration (Cmax) of Cysteine Adduct of Maleimidocaproyl Monomethyl Auristatin F (Cys-mcMMAF)

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)
Reported as:
Mean · ng/mL
Maximum Serum Concentration (Cmax) of Cysteine Adduct of Maleimidocaproyl Monomethyl Auristatin F (Cys-mcMMAF)
ng/mLAGS-16C3F
Cycle 16.09 ± 4.08
Cycle 43.78 ± 1.70
SecondaryMean Predose Serum Concnetration (Ctrough) of Cys-mcMMAF

Ctrough of Cys-mcMMAF was reported.

Time frame:
Predose on cycle 2, 3, 4, 6, 14, and 18 (each cycle is 21 days)
Reported as:
Mean · ng/mL
Mean Predose Serum Concnetration (Ctrough) of Cys-mcMMAF
ng/mLAGS-16C3F
Cycle 60.307 ± NA
SecondaryTime to Maximum Observed Serum Concentration (Tmax) of Cys-mcMMAF

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)
Reported as:
Median · Days
Time to Maximum Observed Serum Concentration (Tmax) of Cys-mcMMAF
DaysAGS-16C3F
Cycle 10.207 (0.139 to 0.954)
Cycle 40.208 (0.197 to 1.11)
SecondaryArea Under the Concentration Versus Time Curve From Time Zero to 21days (AUC0 to 21) of Cys-mcMMAF

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)
Reported as:
Mean · day*ng/mL
Area Under the Concentration Versus Time Curve From Time Zero to 21days (AUC0 to 21) of Cys-mcMMAF
day*ng/mLAGS-16C3F
Cycle 19.61 ± 10.3
SecondaryTerminal Elimination Half-life (t1/2) of Cys-mcMMAF

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)
Reported as:
Median · Days
Terminal Elimination Half-life (t1/2) of Cys-mcMMAF
DaysAGS-16C3F
Cycle 12.72 (2.72 to 2.72)

Adverse events

Collected over From first dose up to 53 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
AGS-16C3F36/67 (53.7%)26/66 (39.4%)65/66 (98.5%)
Axitinib44/66 (66.7%)31/65 (47.7%)64/65 (98.5%)
Most frequent serious events
Showing 10 of 88
Most frequent serious events
EventAGS-16C3FAxitinib
DehydrationMetabolism and nutrition disorders0/664/65
Abdominal painGastrointestinal disorders3/660/65
DiarrhoeaGastrointestinal disorders1/662/65
PneumoniaInfections and infestations0/662/65
Back painMusculoskeletal and connective tissue disorders0/662/65
Pain in extremityMusculoskeletal and connective tissue disorders0/662/65
Confusional statePsychiatric disorders1/662/65
Acute kidney injuryRenal and urinary disorders1/662/65
DyspnoeaRespiratory, thoracic and mediastinal disorders1/662/65
PneumothoraxRespiratory, thoracic and mediastinal disorders0/662/65
Most frequent other events
Showing 10 of 83
Most frequent other events
EventAGS-16C3FAxitinib
FatigueGeneral disorders36/6637/65
DiarrhoeaGastrointestinal disorders12/6631/65
NauseaGastrointestinal disorders31/6626/65
HypertensionVascular disorders4/6627/65
Vision blurredEye disorders26/667/65
DysphoniaRespiratory, thoracic and mediastinal disorders1/6625/65
Decreased appetiteMetabolism and nutrition disorders14/6624/65
Back painMusculoskeletal and connective tissue disorders11/6624/65
VomitingGastrointestinal disorders18/6622/65
ConstipationGastrointestinal disorders16/6621/65

Baseline characteristics

Full Analysis Set (FAS): All participants who were randomized to study drug.

Age, Continuous
Age, Continuous(Years)AGS-16C3FAxitinibTotal
Mean62.3 ± 9.161.1 ± 8.961.7 ± 9
Sex: Female, Male
Sex: Female, Male(Participants)AGS-16C3FAxitinibTotal
Female181735
Male494998
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)AGS-16C3FAxitinibTotal
Hispanic or Latino336
Not Hispanic or Latino6462126
Unknown or Not Reported011
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)AGS-16C3FAxitinibTotal
Race — White5956115
Race — Asian6713
Race — American Indian or Alaska Native112
Race — Other123
Eastern Cooperative Oncology Group (ECOG) Performance Status
Eastern Cooperative Oncology Group (ECOG) Performance Status(Participants)AGS-16C3FAxitinibTotal
0191938
1484795
Histological Type
Histological Type(Participants)AGS-16C3FAxitinibTotal
Clear cell5555110
Non-clear cell121123
Prognostic Risk Group
Prognostic Risk Group(Participants)AGS-16C3FAxitinibTotal
Favorable (0 risk factors)51015
Intermediate (1-2 risk factors)484391
Poor (>=3 risk factors)141327
Number of Prior Systemic Renal cell carcinoma (RCC) Treatment Regimens
Number of Prior Systemic Renal cell carcinoma (RCC) Treatment Regimens(Participants)AGS-16C3FAxitinibTotal
2 if clear cell or 1 if non-clear cell histology353368
>2 if clear cell or >1 if non-clear cell histology323365
08

Study locations

26 sites
  • Site US01026
    Tucson, Arizona 85719, United States
  • Site US01008
    La Jolla, California 92093, United States
  • Site US01007
    Los Angeles, California 90033, United States
  • Site US01020
    Los Angeles, California 90095, United States
  • Site US01019
    Palo Alto, California 94305, United States
  • Site US01010
    Atlanta, Georgia 30322, United States
  • Site US01023
    Baltimore, Maryland 21201, United States
  • Site US01002
    Boston, Massachusetts 02215, United States
  • Site US01004
    Ann Arbor, Michigan 48109, United States
  • Site US01013
    Detroit, Michigan 48202, United States
  • Site US01012
    Omaha, Nebraska 68130, United States
  • Site US01006
    Buffalo, New York 14263, United States
  • Site US01022
    Durham, North Carolina 27710, United States
  • Site US01017
    Portland, Oregon 97213, United States
  • Site US01021
    Pittsburgh, Pennsylvania 15232, United States
  • Site US01011
    Charleston, South Carolina 29425, United States
  • Site US01003
    Houston, Texas 77030, United States
  • Site US01014
    Temple, Texas 76508, United States
  • Site US01001
    Seattle, Washington 98109, United States
  • Site US01009
    Milwaukee, Wisconsin 53226, United States
  • Site CA02006
    Calgary, Alberta T2N 4N2, Canada
  • Site CA02004
    Edmonton, Alberta T6G 1Z2, Canada
  • Site CA02005
    Kelowna, British Columbia V1Y 5L3, Canada
  • Site CA02001
    Vancouver, British Columbia V5Z 4E6, Canada
  • Site CA02002
    Hamilton, Ontario L8V 5C2, Canada
  • Site CA02008
    London, Ontario N6A 5W9, Canada
09

References and documents

Study documents

  • Study protocol · Aug 12, 2020
  • Statistical analysis plan · Jun 10, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Supporting information: Study protocol, Sap, Csr

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 18, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02639182
Lead sponsor
Astellas Pharma Global Development, Inc.
Responsible party
Sponsor
First posted
Dec 24, 2015
Start date
May 3, 2016
Primary completion
Oct 2, 2020
Completion
Oct 2, 2020
Results posted
Sep 23, 2020
Last update
Nov 18, 2024

Study contacts

Associate Medical Director
study director · Astellas Pharma Global Development, Inc.

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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