Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04522323
Recruitment Status : Recruiting
First Posted : August 21, 2020
Last Update Posted : June 1, 2022
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

Brief Summary:
The purpose of this study is to evaluate MEDI5752 in combination with Lenvatinib (or Axitinib), in subjects with advanced renal cell carcinoma.

Condition or disease Intervention/treatment Phase
Advanced Renal Cell Carcinoma Biological: MEDI5752 Drug: Axitinib Drug: Lenvatinib Phase 1

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 Lenvatinib (or Axitinib) in subjects with advanced renal cell carcinoma.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 5, 2020
Estimated Primary Completion Date : February 9, 2024
Estimated Study Completion Date : February 9, 2024


Arm Intervention/treatment
Experimental: Dose Exploration
The Dose exploration Phase is made up of Part A and Part B. Part A will evaluate the safety and tolerability of MEDI5752 in combination with Axitinib (2 patients), and Part B will evaluate the safety and tolerability of MEDI5752 in combination with Lenvatinib (~27 patients)
Biological: MEDI5752
MEDI5752

Drug: Axitinib
INLYTA

Drug: Lenvatinib
LENVIMA

Experimental: Dose Expansion
Evaluate safety and anti-tumor activity of MEDI5752 in combination with Lenvatinib (~41 patients )
Biological: MEDI5752
MEDI5752

Drug: Axitinib
INLYTA

Drug: Lenvatinib
LENVIMA




Primary Outcome Measures :
  1. Number of subjects experiencing adverse events (AEs)/serious adverse events (SAEs) [ Time Frame: Informed consent through 90-Day Post Last Dose. ]
    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.

  2. Number of Participants With Dose Limiting Toxicities (DLT) of MEDI5752 and Lenvatinib (or Axitinib) during the Dose Exploration period. [ Time Frame: Informed consent through the first 21 days of treatment with MEDI5752 and Lenvatinib (or Axitinib) in the Dose Exploration Period. ]

    Determine the MTD and recommended Phase 2 dose (RP2D) of the combination of MEDI5752 and Lenvatinib.

    A dose limiting toxicity (DLT) is defined as MEDI5752 treatment-related AE of any Grade 3 or higher toxicity (as defined in the protocol) CTCAE v5.0.


  3. Number of subjects experiencing adverse events (AEs) leading to discontinuation. [ Time Frame: Informed consent through 90-Day Post Last Dose. ]
    The primary safety endpoint is as assessed by the number of subjects with serious adverse events (SAEs) graded per NCI CTCAE v5.0.

  4. Number of subjects experiencing abnormal laboratory evaluations. [ Time Frame: Informed Consent through 90 post treatment date. ]
    The primary safety endpoint is as assessed by the number of subjects experiencing changes in laboratory evaluations from baseline.

  5. Number of subjects experiencing changes in vital signs reported as Adverse Events. [ Time Frame: Informed consent through 90-Day Post Last Dose ]
    The primary safety endpoint is assessed by the change in vital signs from baseline.

  6. Number of subjects experiencing abnormal electrocardiograms (ECG) reported as Adverse Events. [ Time Frame: Informed consent through 90-Day Post Last Dose ]
    The primary safety endpoint is as assessed by the change in ECG parameters from baseline.

  7. Preliminary antitumor activity of MEDI5752 combined with Lenvatinib (or Axitinib) by Objective response rate per RECIST version (v) 1.1. [ Time Frame: First subject enrolled through 18 months from last subject enrolled, an average of 30 months. ]
    The primary efficacy endpoint is assessed by the antitumor activity of MEDI5752 combined with Lenvatinib.


Secondary Outcome Measures :
  1. Antitumor activity of MEDI5752 combined with Lenvatinib 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. ]
    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.

  2. Antitumor activity of MEDI5752 combined with Lenvatinib 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. ]
    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

  3. Antitumor activity of MEDI5752 combined with Lenvatinib 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 ]
    The endpoint for assessment of DCR is measured by the proportion of subjects with a BOR of confirmed CR, PR, or SD.

  4. Antitumor activity of MEDI5752 combined with Lenvatinib 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 ]
    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.

  5. Antitumor activity of MEDI5752 combined with Lenvatinib 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 ]
    The endpoint for assessment of TTR is defined as the time from the first dose of treatment until the first documentation of an OR.

  6. Pharmacokinetics of MEDI5752: Cmax [ Time Frame: Day 1, 8, 15, 22, 64 and then Day 1 of every other cycle ]
    The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration.

  7. Pharmacokinetics of MEDI5752: AUC [ Time Frame: Day 1, 8, 15, 22, 64 and then Day 1 of every other cycle ]
    The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration.

  8. Pharmacokinetics of MEDI5752: Cmin [ Time Frame: Day 1, 8, 15, 22, 64 and then Day 1 of every other cycle ]
    The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration.

  9. Pharmacokinetics of MEDI5752: t 1/2 [ Time Frame: Day 1, 8, 15, 22, 64 and then Day 1 of every other cycle ]
    The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration.

  10. Pharmacokinetics of MEDI5752: Clearance [ Time Frame: Day 1, 8, 15, 22, 64 and then Day 1 of every other cycle ]
    The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration.

  11. 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 ]
    The endpoints for the immunogenicity of MEDI5752 include the number of subjects who develop detectable anti-drug antibodies (ADAs) to MEDI5752.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 101 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • 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.
  • Strongly recommend nonsterilized male partners of female subjects of childbearing potential use a male condom plus spermicide from screening to 7.6 months after the last dose of MEDI5752 and 30 days after the last dose of lenvatinib.

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 inhibitor
  • Previous treatment with VEGF inhibitors
  • Evidence of the following infections: active infection including tuberculosis, human immunodeficiency virus, chronic or active hepatitis B or chronic or active hepatitis C
  • 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.
  • Poorly controlled blood pressure (BP) defined as systolic BP ≥ 140/90 mmHg at screening and not able to be controlled prior to Cycle 1 Day 1 and any change in antihypertensive medications within 1 week prior to Cycle 1 Day 1.
  • 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 or has not recovered from AEs due to prior treatment
  • 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, or asymptomatic sustained ventricular tachycardia
  • Uncontrolled intercurrent illness within the last 6 months prior to enrollment
  • Clinically significant gastrointestinal abnormality
  • Serious nonhealing wound, ulcer, or bone fracture
  • Has clinically significant hemoptysis (at least 0.5 teaspoon of bright red blood) or tumor bleeding within 2 weeks before the first dose of investigational product
  • Radiographic evidence of major blood vessel invasion/infiltration/encasement

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04522323


Contacts
Layout table for location contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
Layout table for location information
United States, California
Research Site Not yet recruiting
Duarte, California, United States, 91010
United States, District of Columbia
Research Site Completed
Washington, District of Columbia, United States, 20007
United States, Florida
Research Site Suspended
Fort Myers, Florida, United States, 33908
United States, Missouri
Research Site Suspended
Saint Louis, Missouri, United States, 63156
United States, New Jersey
Research Site Not yet recruiting
Hackensack, New Jersey, United States, 07601
United States, New York
Research Site Recruiting
New York, New York, United States, 10065
United States, Ohio
Research Site Recruiting
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Research Site Recruiting
Hershey, Pennsylvania, United States, 17033
United States, Tennessee
Research Site Recruiting
Nashville, Tennessee, United States, 37232
Australia
Research Site Recruiting
Frankston, Australia, 3199
Research Site Withdrawn
Melbourne, Australia, 3000
Research Site Recruiting
Waratah, Australia, 2298
France
Research Site Recruiting
Villejuif Cedex, France, 94805
Spain
Research Site Recruiting
Barcelona, Spain, 08003
Research Site Recruiting
Barcelona, Spain, 08025
Research Site Recruiting
Barcelona, Spain, 08035
Research Site Recruiting
Barcelona, Spain, 08908
Research Site Not yet recruiting
Córdoba, Spain, 14004
Research Site Not yet recruiting
Madrid, Spain, 28040
Research Site Recruiting
Madrid, Spain, 28041
Research Site Recruiting
Sabadell, Spain, 08208
Research Site Recruiting
Sevilla, Spain, 41013
Research Site Recruiting
Valencia, Spain, 46009
Sponsors and Collaborators
MedImmune LLC
Investigators
Layout table for investigator information
Study Director: AstraZeneca Early Oncology AstraZeneca
Layout table for additonal information
Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT04522323    
Other Study ID Numbers: D7980C00003
First Posted: August 21, 2020    Key Record Dates
Last Update Posted: June 1, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by MedImmune LLC:
renal cell carcinoma
MEDI5752
PD-1/CTLA-4 bispecific
PD-1
CTLA-4
bispecific
axitinib
lenvatinib
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Lenvatinib
Axitinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action