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

MedImmune LLC39 enrolled

Overview

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.

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Advanced Solid Tumors

Interventions

MEDI5083 monotherapyBIOLOGICAL

Dose-escalation MEDI5083 monotherapy followed by monotherapy with Durvalumab

MEID5083 with Durvalumab or TremelimumabBIOLOGICAL

Sequential Medi5083 with concurrent Durvalumab or Tremelimumab, and intermittent Medi5083 with concurrent Durvalumab

Medi5083 with Durvalumab and DocetaxelBIOLOGICAL

Medi5083 with concurrent Durvalumab and Docetaxel randomized against Durvalumab and Docetaxel

Eligibility

Sex: ALLMin age: 18 YearsMax age: 101 Years

Medical Language ↔ Plain English

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

Locations (8)

Research Site

Hackensack, New Jersey, United States

Research Site

Providence, Rhode Island, United States

Research Site

Nashville, Tennessee, United States

Research Site

Salt Lake City, Utah, United States

Outcomes

Primary Outcomes

Number of participants with Adverse Events (AEs) as a measure of safety

Safety Endpoint

Time frame: 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

Time frame: 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

Time frame: From the time of first dose through 28 days thereafter

The Maximum Tolerated Dose (MTD) or Highest Protocol-Defined Dose

Safety Endpoint

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Part 3

Secondary Outcomes

Data from ClinicalTrials.gov

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Serum MEDI5083 concentration levels

Pharmacokinetics (PK)

Time frame: From the time of first dose through 57 days after first treatment

Reduction in peripheral blood CD19+ B cells

Pharmacodynamics (PD)

Time frame: From the time of first dose through 57 days after first treatment

Incidence of anti-drug antibody (ADA) responses to MEDI5083

Immunogenicity

Time frame: From the time of first dose through 2 years after last treatment

Objective Response Rate (ORR)

Clinical Activity Endpoint

Time frame: 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

Time frame: From the time of first dose until 6 months after the last subject is dosed

Overall Survival (OS)

Clinical Activity Endpoint

Time frame: 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

Time frame: 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

Time frame: 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)

Time frame: From the time of first dose through 29 days after first treatment

Incidence of anti-drug antibody (ADA) responses to Durvalumab

Immunogenicity

Time frame: From the time of first dose through 2 years after last treatment

Incidence of anti-drug antibody (ADA) responses to tremelilumab

Immunogenicity

Time frame: From the time of first dose through 2 years after last treatment

Serum tremelimumab concentration levels collected over time

Pharmacodynamics (PD)

Time frame: 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)

Time frame: 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

Time frame: From the time of first dose through 57 days after first treatment