Clinical Trials /

A Study to Evaluate MEDI5752 and Axitinib in Subjects With Advanced Renal Cell Carcinoma

NCT04522323

Description:

The purpose of this study is to evaluate MEDI5752 in combination with axitinib.in subjects with advanced renal cell carcinoma.

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

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate MEDI5752 and Axitinib in Subjects With Advanced Renal Cell Carcinoma
  • Official Title: A Phase 1b, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI5752 in Combination With Axitinib in Subjects With Advanced Renal Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: D7980C00003
  • NCT ID: NCT04522323

Conditions

  • Advanced Renal Cell Carcinoma

Interventions

DrugSynonymsArms
MEDI5752Dose Expansion
AxitinibDose Expansion

Purpose

The purpose of this study is to evaluate MEDI5752 in combination with axitinib.in subjects with advanced renal cell carcinoma.

Detailed Description

      The purpose of this Phase 1b study is to evaluate the safety, tolerability, pharmacokinetics,
      immunogenicity, and antitumor activity of MEDI5752 in combination with axitinib in subjects
      with advanced renal cell carcinoma.
    

Trial Arms

NameTypeDescriptionInterventions
Dose ExplorationExperimentalThe Dose exploration Phase will evaluate the safety and tolerability of MEDI5752 in combination with axitinib (18 patients)
  • MEDI5752
  • Axitinib
Dose ExpansionExperimentalEvaluate safety and anti-tumor activity of MEDI5752 in combination with axitinib (50 pts)
  • MEDI5752
  • Axitinib

Eligibility Criteria

        Inclusion Criteria:

          -  Age ≥ 18 at the time of screening

          -  Body weight > 35 kg

          -  Written informed consent

          -  Histologically or cytologically proven advanced RCC with clear cell component

          -  Advanced RCC not previously treated in that setting

          -  Provision of tumor material (≥ 5 unstained slides or tissue block) from an archival or
             fresh tissue sample if clinically feasible

          -  ECOG performance status of 0 or 1

          -  Subjects must have at least 1 measurable lesion according to RECIST v1.1

          -  Life expectancy ≥ 12 weeks

          -  Adequate organ and marrow function

          -  Female subjects of childbearing potential must have negative pregnancy test at
             screening and prior to each administration of investigational product, and must use at
             least one highly effective method of contraception.

        Exclusion Criteria:

          -  Any condition that, in the opinion of the investigator, would interfere with
             evaluation of the investigational product or interpretation of subject safety or study
             results

          -  Concurrent enrollment in another clinical study, unless it is an observational study.

          -  Previous treatment with mTOR inhibitors, PD-1, PD-L1, or CTLA-4 inhibitors for RCC or
             any other immune checkpoint inhibitors

          -  Previous treatment with axitinib; other VEGF TKIs used in the adjuvant setting are
             allowed if last dose > 6 months prior to the first dose of investigational product

          -  History of active primary immunodeficiency:

          -  History of organ transplant

          -  Active or prior documented autoimmune or inflammatory disorders

          -  Current or prior use of immunosuppressive medication within 14 days prior to the first
             dose of investigational product.

          -  Has poorly controlled hypertension defined as systolic BP ≥ 140 mm Hg and/or diastolic
             BP ≥ 90 mm Hg.

          -  Thromboembolic (arterial or venous) events within previous 6 months

          -  Any concurrent therapy for cancer

          -  Receipt of live attenuated vaccine within 30 days prior to the first dose of
             investigational product

          -  Known allergy or hypersensitivity to investigational product(s) or any of the
             excipients of the investigational product(s)

          -  Untreated or progressive CNS metastatic disease, any leptomeningeal disease, or cord
             compression

          -  History of another primary malignancy

          -  Unresolved toxicities from previous anticancer therapy

          -  Major surgery within 4 weeks prior to enrollment or radiation therapy within 2 weeks
             prior to enrollment,

          -  Female subjects who are pregnant or breastfeeding as well as male or female subjects
             of reproductive potential who are not willing to employ one highly effective method of
             birth control as described in inclusion criteria

          -  History of arrhythmia which is symptomatic or requires treatment symptomatic or
             uncontrolled atrial fibrillation despite treatment

          -  Uncontrolled intercurrent illness within the last 6 months prior to enrollment

          -  Clinically significant gastrointestinal abnormality

          -  Evidence of inadequate wound healing

          -  Current use or anticipated need for treatment with drugs or foods that are known
             strong CYP3A4/5 inhibitors
      
Maximum Eligible Age:101 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of subjects experiencing advese events (AEs)/serious adverse events (SAEs)
Time Frame:Informed consent through 90-Day Post Last Dose.
Safety Issue:
Description:The primary safety endpoint is as assessed by the number of subjects with adverse events and serious adverse events (SAEs) graded per NCI CTCAE v5.0.

Secondary Outcome Measures

Measure:Antitumor activity of MEDI5752 and axitinib by measuring the progression free survival (PFS) according to RECIST v1.1.
Time Frame:Last Subject Enrolled through study completion, an average of 48 months.
Safety Issue:
Description:The endpoint for assessment of PFS is defined as the time from the first dose of treatment until the documentation of PD or death due to any cause, whichever occurs first.
Measure:Antitumor activity of MEDI5752 and axitinib by measuring the Best Overall Response (BOR) according to RECIST v1.1.
Time Frame:First subject enrolled through 18 months from last subject enrolled, an average of 30 months.
Safety Issue:
Description:The endpoint for assessment of BOR will be based on all post-baseline disease assessments that occur prior to the initiation of subsequent anticancer treatment
Measure:Antitumor activity of MEDI5752 and axitinib by measuring the Disease Control Rate (DCR).
Time Frame:Informed Consent through the date of first documented progression, end of study, date of death, or two years after last subject starts treatment whichever should occur first
Safety Issue:
Description:The endpoint for assessment of DCR is measured by the proportion of subjects with a BOR of confirmed CR, PR, or SD.
Measure:Antitumor activity of MEDI5752 and axitinib by measuring the Duration of Response (DOR) according to RECIST v1.1.
Time Frame:Informed Consent through the date of first documented progression, end of study, date of death, or two years after last subject starts treatment whichever should occur first
Safety Issue:
Description:The endpoint for assessment of DOR is measured by the duration from the first documented OR to the first documented PD or death due to any cause, whichever occurs first.
Measure:Antitumor activity of MEDI5752 and axitinib by measuring the Time to Response (TTR) according to RECIST v1.1.
Time Frame:Informed Consent through the date of first documented progression, end of study, date of death, or two years after last subject starts treatment whichever should occur first
Safety Issue:
Description:The endpoint for assessment of TTR is defined as the time from the first dose of treatment until the first documentation of an OR.
Measure:Pharmacokinetics of MEDI5752: Cmax
Time Frame:Day 1,8,15, 22,64 and then Day 1 of every other cycle
Safety Issue:
Description:The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration.
Measure:Pharmacokinetics of MEDI5752: AUC
Time Frame:Day 1,8,15, 22,64 and then Day 1 of every other cycle
Safety Issue:
Description:The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration.
Measure:Pharmacokinetics of MEDI5752: Cmin
Time Frame:Day 1,8,15, 22,64 and then Day 1 of every other cycle
Safety Issue:
Description:The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration.
Measure:Pharmacokinetics of MEDI5752: t 1/2
Time Frame:Day 1,8,15, 22,64 and then Day 1 of every other cycle
Safety Issue:
Description:The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration.
Measure:Pharmacokinetics of MEDI5752: Clearance
Time Frame:Day 1,8,15, 22,64 and then Day 1 of every other cycle
Safety Issue:
Description:The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration.
Measure:Immunogencity of MEDI572: Incidence of ADAs against MEDI5752
Time Frame:Day 1,8,15, 22,30,64 and then Day 1 of every other cycle
Safety Issue:
Description:Immunogenicity of MEDI5752: The endpoints for the immunogenicity of MEDI5752 include the number of subjects who develop detectable anti-drug antibodies (ADAs) to MEDI5752.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:MedImmune LLC

Trial Keywords

  • renal cell carcinoma

Last Updated

August 19, 2020