Clinical Trials /

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

NCT02639182

Description:

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.

Related Conditions:
  • Clear Cell Renal Cell Carcinoma
  • Renal Cell Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of AGS-16C3F vs. Axitinib in Metastatic Renal Cell Carcinoma
  • Official Title: A Multi-Center, Open Label, Randomized Phase 2 Study of AGS-16C3F vs. Axitinib in Metastatic Renal Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: AGS-16C3F-15-3
  • NCT ID: NCT02639182

Conditions

  • Metastatic Renal Cell Carcinoma

Interventions

DrugSynonymsArms
AGS-16C3FAGS-16C3F
AxitinibInlyta®Axitinib

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
AGS-16C3FExperimentalParticipants received 1.8 milligram per kilogram (mg/kg) of AGS-16C3F once every three weeks by single intravenous (IV) infusion.
  • AGS-16C3F
AxitinibActive ComparatorParticipants received 2 to 10 milligram (mg) of axitinib twice daily by oral administration as defined in the product label and per local institutional guidelines.
  • Axitinib

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Investigator Radiologic Review
Time Frame:From date of randomization to the earliest of either documented disease progression or death from any cause (up to 40 months)
Safety Issue:
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.

Secondary Outcome Measures

Measure:PFS Per RECIST v1.1 as Assessed by Blinded Central Radiology Assessment
Time Frame:From date of randomization to the earliest of either documented disease progression or death from any cause (up to 40 months)
Safety Issue:
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.
Measure:Objective Response Rate (ORR) Based on the Investigator's Radiographic Assessment
Time Frame:From date of randomization until data cutoff date of 21 August 2019 (up to 40 months)
Safety Issue:
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.
Measure:Duration of Response (DOR) Based on the Investigator's Radiographic Assessment
Time Frame:From date of first objective response until data cutoff date of 21 August 2019 (up to 40 months)
Safety Issue:
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.
Measure:Overall Survival (OS)
Time Frame:Date of randomization until the date of death from any cause (up to 40 months)
Safety Issue:
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.
Measure:Disease Control Rate (DCR) Based on the Investigator's Radiographic Assessment
Time Frame:Date of randomization until data cutoff date of 21 August 2019 (up to 40 months)
Safety Issue:
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.
Measure:Number of Participants With Adverse Events
Time Frame:From first dose Up to 40 months
Safety Issue:
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.
Measure:Maximum Observed Serum Concentration (Cmax) of Antibody Drug Conjugate (ADC)
Time Frame:Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)
Safety Issue:
Description:Cmax of ADC was reported.
Measure:Mean Predose Serum Concentration (Ctrough) of ADC
Time Frame:Predose on cycle 2, 3, 4, 6, 14, and 18 (each cycle is 21 days)
Safety Issue:
Description:Ctrough of ADC was reported.
Measure:Time to Maximum Observed Serum Concentration (Tmax) of ADC
Time Frame:Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)
Safety Issue:
Description:Tmax of ADC was reported.
Measure:Area Under the Concentration Versus Time Curve From Time Zero to 21days (AUC0 to 21) of ADC
Time Frame:Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)
Safety Issue:
Description:AUC (0 to 21) of ADC was reported.
Measure:Terminal Elimination Half-life (t1/2) of ADC
Time Frame:Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)
Safety Issue:
Description:t1/2 of ADC was reported.
Measure:Maximum Serum Concentration (Cmax) of Total Antibody (TAb)
Time Frame:Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)
Safety Issue:
Description:Cmax of TAb was reported.
Measure:Mean Predose Serum Concnetration (Ctrough) of TAb
Time Frame:Predose on cycle 2, 3, 4, 6, 14, and 18 (each cycle is 21 days)
Safety Issue:
Description:Ctrough of TAb was reported.
Measure:Time to Maximum Observed Serum Concentration (Tmax) of Tab
Time Frame:Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)
Safety Issue:
Description:Tmax of TAb was reported.
Measure:Area Under the Concentration Versus Time Curve From Time Zero to 21days (AUC0 to 21) of TAb
Time Frame:Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)
Safety Issue:
Description:AUC (0 to 21) of TAb was reporetd.
Measure:Terminal Elimination Half-life (t1/2) of Tab
Time Frame:Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)
Safety Issue:
Description:t1/2 of TAb was reported.
Measure:Maximum Serum Concentration (Cmax) of Cysteine Adduct of Maleimidocaproyl Monomethyl Auristatin F (Cys-mcMMAF)
Time Frame:Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)
Safety Issue:
Description:Cmax of Cys-mcMMAF was reported.
Measure:Mean Predose Serum Concnetration (Ctrough) of Cys-mcMMAF
Time Frame:Predose on cycle 2, 3, 4, 6, 14, and 18 (each cycle is 21 days)
Safety Issue:
Description:Ctrough of Cys-mcMMAF was reported.
Measure:Time to Maximum Observed Serum Concentration (Tmax) of Cys-mcMMAF
Time Frame:Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)
Safety Issue:
Description:Tmax of Cys-mcMMAF was reported.
Measure:Area Under the Concentration Versus Time Curve From Time Zero to 21days (AUC0 to 21) of Cys-mcMMAF
Time Frame:Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)
Safety Issue:
Description:AUC (0 to 21) of Cys-mcMMAF was reporetd.
Measure:Terminal Elimination Half-life (t1/2) of Cys-mcMMAF
Time Frame:Predose, end of infusion, 4, 24, 72, 336 hours postdose of cycle 1 and cycle 4 (each cycle is 21 days)
Safety Issue:
Description:t1/2 of Cys-mcMMAF was reported

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Astellas Pharma Global Development, Inc.

Trial Keywords

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

Last Updated

May 19, 2021