MEDI5083 Alone and in Combination With Durvalumab, Tremelimumab, and/or Docetaxel.

A Phase 1 First Time in Human Study to Evaluate the Safety, Pharmacokinetics and Immunogenicity of MEDI5083 Alone or in Combination With Durvalumab, Tremelimumab, and/or Docetaxel in Advanced Solid Tumors

The purpose of this study is to evaluate the safety, pharmacokinetics and Immunogenicity of Medi5083 alone or in combination with Durvalumab,Tremelimumab, and/or Docetaxel in adult subjects with advanced solid tumors.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Biological: MEDI5083 monotherapy; Biological: MEID5083 with Durvalumab or Tremelimumab; Biological: Medi5083 with Durvalumab and Docetaxel

Detailed Description

This is a global Phase 1, first-time-in-human, multicenter, dose-escalation and dose-expansion study of MEDI5083 alone or in combination with Durvalumab, Tremelimumab, and/or Docetaxel.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Clayton, Australia, 3168
    • Research Site
  • Melbourne, Australia, 3004
    • Research Site
  • Melbourne, Australia, 3000
    • Research Site
  • Randwick, Australia, 2031
    • Research Site
• United States
  • New Jersey
    • Hackensack, New Jersey, United States, 07601-2191
      • Research Site
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Research Site
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 97 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 years at the time of screening or age of consent according to local law
2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
3. Histologically or cytologically confirmed metastatic or recurrent tumor types
4. Subjects who have received prior immunotherapy may be eligible
5. Subjects must have at least one measurable lesion
6. Consent to provide archival tumor tissue and pre/on-treatment biopsies
7. Adequate organ and marrow function
8. Consent to use one highly effective method of contraception

Exclusion Criteria:

1. Receipt of any systemic anticancer therapy within 28 days prior to the first dose of MEDI5083
2. Concurrent enrollment in another clinical study
3. Active/prior autoimmune of inflammatory disorders
4. History of immunodeficiency, solid organ transplant, or tuberculosis
5. Known allergy/hypersensitivity to drug or components
6. Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression
7. Current or prior use of immunosuppressive medication within 14 days prior to the first dose of MEDI5083

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1; MEDI5083 monotherapy followed by Durvalumab monotherapy in subjects with advanced solid tumors	Biological: MEDI5083 monotherapy; Dose-escalation MEDI5083 monotherapy followed by monotherapy with Durvalumab
Experimental: Part 2; Sequential MEDI5083 with concurrent Durvalumab or Tremelimumab, and intermittent Medi5083 with concurrent Durvalumab in subjects with advanced solid tumors.	Biological: MEID5083 with Durvalumab or Tremelimumab; Sequential Medi5083 with concurrent Durvalumab or Tremelimumab, and intermittent Medi5083 with concurrent Durvalumab
Experimental: Part 3; Medi5083 with concurrent Durvalumab and Docetaxel randomized against Durvalumab and Docetaxel in subjects with IO refractory/relapsed 2/3L in NSCLC	Biological: Medi5083 with Durvalumab and Docetaxel; Medi5083 with concurrent Durvalumab and Docetaxel randomized against Durvalumab and Docetaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Adverse Events (AEs) as a measure of safety	Safety Endpoint	From the time of consent through 120 days after last treatment
Number of participants with Serious Adverse Events (SAEs) as a measure of safety	Safety Endpoint	From the time of consent through 120 days after last treatment
Number of participants with Dose Limiting Toxicities (DLTs) as a measure of safety	Safety Endpoint	From the time of first dose through 28 days thereafter
The Maximum Tolerated Dose (MTD) or Highest Protocol-Defined Dose	Safety Endpoint	From the time of first dose through end of study (2 years after last subject enrolled or earlier at sponsor discretion)
Discontinuation of investigational products due to toxicity	Safety Endpoint	From the time of first dose through end of study (2 years after last subject enrolled or earlier at sponsor discretion)
Clinically significant alterations in vital signs, laboratory parameters, physical examination, and electrocardiogram (ECG) results.	Safety Endpoint	From the time of first dose through end of study (2 years after last subject enrolled or earlier at sponsor discretion)
Antitumor activity endpoints OR, based on RECIST v1.1	Safety Endpoint	Part 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum MEDI5083 concentration levels	Pharmacokinetics (PK)	From the time of first dose through 57 days after first treatment
Reduction in peripheral blood CD19+ B cells	Pharmacodynamics (PD)	From the time of first dose through 57 days after first treatment
Incidence of anti-drug antibody (ADA) responses to MEDI5083	Immunogenicity	From the time of first dose through 2 years after last treatment
Objective Response Rate (ORR)	Clinical Activity Endpoint	From the time of consent through end of study (2 years after last subject enrolled or earlier at sponsor discretion)
Progression Free Survival (PFS) at 6 months (PFS-6)	Clinical Activity Endpoint	From the time of first dose until 6 months after the last subject is dosed
Overall Survival (OS)	Clinical Activity Endpoint	From the time of consent through end of study (2 years after last subject enrolled or earlier at sponsor discretion)
Disease Control Rate (DCR)	Clinical Activity Endpoint	From the time of consent through end of study (2 years after last subject enrolled or earlier at sponsor discretion)
Duration of Response (DoR)	Clinical Activity Endpoint	From the time of consent through end of study (2 years after last subject enrolled or earlier at sponsor discretion)
Serum Durvalumab concentration levels collected over time	Pharmacokinetics (PK)	From the time of first dose through 29 days after first treatment
Incidence of anti-drug antibody (ADA) responses to Durvalumab	Immunogenicity	From the time of first dose through 2 years after last treatment
Incidence of anti-drug antibody (ADA) responses to tremelilumab	Immunogenicity	From the time of first dose through 2 years after last treatment
Serum tremelimumab concentration levels collected over time	Pharmacodynamics (PD)	From the time of first dose through 57 days after first treatment
PD of MEDI5083 alone and in combination with Durvalumab and tremelimumab	Pharmacodynamics (PD)	From the time of first dose through 57 days after first treatment
Safety and tolerability of MEDI5083 with durvalumamb and docetaxel and in subjects with IO relapsed/refractory 2/3L NSCLC	Safety	From the time of first dose through 57 days after first treatment

Collaborators and Investigators

• Sponsor: MedImmune LLC

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2017
• Primary Completion (Actual): June 23, 2020
• Study Completion (Actual): June 23, 2020

Study Registration Dates

• First Submitted: January 19, 2017
• First Submitted That Met QC Criteria: March 20, 2017
• First Posted (Actual): March 24, 2017

Study Record Updates

• Last Update Posted (Actual): July 27, 2020
• Last Update Submitted That Met QC Criteria: July 24, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Docetaxel; Durvalumab; Tremelimumab; Antibodies, Monoclonal
• Other Study ID Numbers: D6840C00001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No