Clinical Trials /

A Study to Evaluate MEDI5752 in Subjects With Advanced Solid Tumors

NCT03530397

Description:

The purpose of this study is to evaluate MEDI5752 in adult subjects with advanced solid tumors, when administered as a single agent or combined with chemotherapy.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate MEDI5752 in Subjects With Advanced Solid Tumors
  • Official Title: A Phase 1, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI5752 in Subjects With Advanced Solid Tumors.

Clinical Trial IDs

  • ORG STUDY ID: D7980C00001
  • NCT ID: NCT03530397

Conditions

  • Selected Advanced Solid Tumors
  • NSCLC
  • Lung Cancer

Interventions

DrugSynonymsArms
MEDI5752Arm A: MEDI5752
DurvalumabArm B: durvalumab
PemetrexedArm C: MEDI5752 and chemotherapy
CarboplatinArm C: MEDI5752 and chemotherapy
PembrolizumabArm D: Pembrolizumab and chemotherapy

Purpose

The purpose of this study is to evaluate MEDI5752 in adult subjects with advanced solid tumors, when administered as a single agent or combined with chemotherapy.

Detailed Description

      This is a phase 1, first-time-in-human, multicenter, open-label, dose-escalation and
      dose-expansion study to evaluate the safety and tolerability, and efficacy, pharmacokinetics
      and Immunogenicity of MEDI5752 in adult subjects with advanced solid tumors, when
      administered as a single agent or combined with chemotherapy.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A: MEDI5752ExperimentalMEDI5752
  • MEDI5752
Arm B: durvalumabActive Comparatordurvalumab
  • Durvalumab
Arm C: MEDI5752 and chemotherapyExperimentalMEDI5752, pemetrexed and carboplatin.
  • MEDI5752
  • Pemetrexed
  • Carboplatin
Arm D: Pembrolizumab and chemotherapyActive Comparatorpembrolizumab, pemetrexed, and carboplatin
  • Pemetrexed
  • Carboplatin
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria

          1. Age ≥ 18 years at the time of screening

          2. World Health Organization/Eastern Cooperative Oncology Group (ECOG) performance status
             of 0 or 1 at enrollment

          3. Life expectancy ≥ 12 weeks

          4. Histologically or cytologically-confirmed advanced solid tumors

          5. Subjects who have received prior anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy or any
             concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy
             for cancer treatment may be eligible to enter the study following a washout period of
             these treatments totaling at least 28 days before the first dose.

          6. Females of childbearing potential who are sexually active with a nonsterilized male
             partner must use at least one highly effective method of contraception

          7. Nonsterilized males who are sexually active with a female partner of childbearing
             potential must use a male condom with spermicide where locally available from Day 1
             and for 90 days after the final dose of investigational product

          8. Subjects must have at least one measurable lesion

          9. Adequate organ and marrow function

         10. Written informed consent and any locally required authorization

         11. Subjects must provide tumor material as applicable

        Exclusion Criteria

          1. Involvement in the planning and/or conduct of the study (applies to both MedImmune
             staff and/or staff at the study site)

          2. Concurrent enrollment in another clinical study, unless it is an observational
             clinical study or the follow-up period of an interventional study

          3. For subjects who have received prior anti-PD-1, anti-PD-L1, or anti-CTLA-4:

               1. Subjects must not have received anti-PD-1, anti-PD-L1, anti-CTLA-4 or any other
                  immunotherapy or immune-oncology (IO) agent within 28 days of commencing
                  treatment with investigational product.

               2. Subject must not have experienced a toxicity that led to permanent
                  discontinuation of prior immunotherapy.

               3. All AEs while receiving prior immunotherapy must have completely resolved or
                  resolved to Grade 1 prior to screening for this study.

          4. Current or prior use of immunosuppressive medication within 14 days before the first
             dose of investigational product is excluded.

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

          6. Active or prior documented autoimmune or inflammatory disorders

          7. History of active primary immunodeficiency:

          8. History of organ transplant that requires use of immunosuppressive therapy

          9. Known allergy or reaction to any component of the planned study treatment.

         10. Untreated CNS metastatic disease, leptomeningeal disease, or cord compression

         11. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to
             NCI CTCAE v4.03 Grade 0 or 1, or to levels dictated in the inclusion/exclusion
             criteria

         12. Major surgical procedure (as defined by the investigator) within 28 days prior to the
             first dose of Investigational Product or still recovering from prior surgery

         13. 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

         14. Uncontrolled intercurrent illness, that would limit compliance with study requirement,
             substantially increase risk of incurring AEs or compromise the ability of the subject
             to give written informed consent.

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

         16. Judgment by the investigator that the subject is unsuitable to participate in the
             study and the subject is unlikely to comply with study procedures, restrictions, and
             requirements.
      
Maximum Eligible Age:120 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The number of subjects experiencing treatment related adverse events (AEs).
Time Frame:From the time of informed consent through 114 days following termination of treatment with investigational product
Safety Issue:
Description:The primary endpoint is as assessed by the number of subjects experiencing adverse events (AEs) graded per NCI CTCAE v4.03

Secondary Outcome Measures

Measure:Pharmacokinetics of MEDI5752: Cmax
Time Frame:To be assessed at Day 1, 2, 3, 8, 15, 22, 29, 43, 64, 85, and 106 over the first 4 months of treatment and up to 114 days following end of treatment
Safety Issue:
Description:The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration. PK parameters that may be modeled on this data include maximum observed concentration (Cmax)
Measure:Pharmacokinetics of MEDI5752: AUC
Time Frame:To be assessed at Day 1, 2, 3, 8, 15, 22, 29, 43, 64, 85, and 106 over the first 4 months of treatment and up to 114 days following end of treatment
Safety Issue:
Description:The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration. PK parameters that may be modeled on this data include area under the concentration-time curve (AUC)
Measure:Pharmacokinetics of MEDI5752: Clearance
Time Frame:To be assessed at Day 1, 2, 3, 8, 15, 22, 29, 43, 64, 85, and 106 over the first 4 months of treatment and up to 114 days following end of treatment
Safety Issue:
Description:The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration. PK parameters that may be modeled on this data include clearance (CL)
Measure:Pharmacokinetics of MEDI5752: t 1/2
Time Frame:To be assessed at Day 1, 2, 3, 8, 15, 22, 29, 43, 64, 85, and 106 over the first 4 months of treatment and up to 114 days following end of treatment.
Safety Issue:
Description:The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration. PK parameters that may be modeled on this data include terminal phase half life (t 1/2)
Measure:Immunogenicity of MEDI5752
Time Frame:To be assessed at Day 1, 8, 15, 22, 29, 43, 64, 85, and 106 over the first 4 months of treatment and up to 114 days following end of treatment.
Safety Issue:
Description:The endpoints for the immunogenicity of MEDI5752 include the number of subjects who develop detectable anti-drug antibodies (ADAs)
Measure:PD-L1 Expression in subjects with advanced solid tumors
Time Frame:To be assessed at at baseline
Safety Issue:
Description:The endpoint for the PD-L1 expression will be determined by Immunohistochemistry characterization.
Measure:Preliminary Antitumor Activity: Duration of Response
Time Frame:From the date of response 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 endpoints for assessment of antitumor activity include duration of response (DoR) and is defined as the duration from the documentation of OR to the first documentation of disease progression or death due to any cause.
Measure:Preliminary Antitumor Activity: Disease Control
Time Frame:From the first dose of study drug 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 endpoints for assessment of antitumor activity include disease control (DC) and is defined as CR, PR, or SD according to RECIST v1.1.
Measure:Preliminary Antitumor Activity: Progression Free Survival
Time Frame:From the first dose of study drug 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 endpoints for assessment of antitumor activity include progression free survival (PFS) and is defined as the duration measured from the start of treatment with investigational product to the first documentation of disease progression or death due to any cause.
Measure:Preliminary Antitumor Activity: Overall Survival
Time Frame:From the first dose of study drug through the end of study, or date of death, or two years after last subject starts treatment whichever should occur first
Safety Issue:
Description:The endpoints for assessment of antitumor activity include overall survival (OS) and is defined as the duration measured from the start of treatment with investigational product until death due to any cause.

Details

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

Trial Keywords

  • Advanced solid tumors
  • NSCLC
  • lung cancer
  • MEDI5752
  • durvalumab
  • immuno-oncology
  • Cancer
  • PD-1/CTLA-4 Bispecific
  • PD-1
  • CTLA-4
  • Bispecific
  • Chemotherapy
  • Pemetrexed
  • Carboplatin
  • Pembrolizumab

Last Updated