Clinical trial NCT03089645: MEDI5083 Alone and in Combination With Durvalumab, Tremelimumab, and/or Docetaxel.
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2017-03-24
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 101
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with Adverse Events (AEs) as a measure of safety
timeFrame: From the time of consent through 120 days after last treatment
measure: Number of participants with Serious Adverse Events (SAEs) as a measure of safety
timeFrame: From the time of consent through 120 days after last treatment
measure: Number of participants with Dose Limiting Toxicities (DLTs) as a measure of safety
timeFrame: From the time of first dose through 28 days thereafter
measure: The Maximum Tolerated Dose (MTD) or Highest Protocol-Defined Dose
timeFrame: From the time of first dose through end of study (2 years after last subject enrolled or earlier at sponsor discretion)
measure: Discontinuation of investigational products due to toxicity
timeFrame: From the time of first dose through end of study (2 years after last subject enrolled or earlier at sponsor discretion)
measure: Clinically significant alterations in vital signs, laboratory parameters, physical examination, and electrocardiogram (ECG) results.
timeFrame: From the time of first dose through end of study (2 years after last subject enrolled or earlier at sponsor discretion)
measure: Antitumor activity endpoints OR, based on RECIST v1.1
timeFrame: Part 3
Secondary outcomes:
measure: Serum MEDI5083 concentration levels
timeFrame: From the time of first dose through 57 days after first treatment
measure: Reduction in peripheral blood CD19+ B cells
timeFrame: From the time of first dose through 57 days after first treatment
measure: Incidence of anti-drug antibody (ADA) responses to MEDI5083
timeFrame: From the time of first dose through 2 years after last treatment
measure: Objective Response Rate (ORR)
timeFrame: From the time of consent through end of study (2 years after last subject enrolled or earlier at sponsor discretion)
measure: Progression Free Survival (PFS) at 6 months (PFS-6)
timeFrame: From the time of first dose until 6 months after the last subject is dosed
measure: Overall Survival (OS)
timeFrame: From the time of consent through end of study (2 years after last subject enrolled or earlier at sponsor discretion)
measure: Disease Control Rate (DCR)
timeFrame: From the time of consent through end of study (2 years after last subject enrolled or earlier at sponsor discretion)
measure: Duration of Response (DoR)
timeFrame: From the time of consent through end of study (2 years after last subject enrolled or earlier at sponsor discretion)
measure: Serum Durvalumab concentration levels collected over time
timeFrame: From the time of first dose through 29 days after first treatment
measure: Incidence of anti-drug antibody (ADA) responses to Durvalumab
timeFrame: From the time of first dose through 2 years after last treatment
measure: Incidence of anti-drug antibody (ADA) responses to tremelilumab
timeFrame: From the time of first dose through 2 years after last treatment
measure: Serum tremelimumab concentration levels collected over time
timeFrame: From the time of first dose through 57 days after first treatment
measure: PD of MEDI5083 alone and in combination with Durvalumab and tremelimumab
timeFrame: From the time of first dose through 57 days after first treatment
measure: Safety and tolerability of MEDI5083 with durvalumamb and docetaxel and in subjects with IO relapsed/refractory 2/3L NSCLC
timeFrame: From the time of first dose through 57 days after first treatment
Other outcomes:
Locations:
city: Hackensack
country: United States
facility: Research Site
state: New Jersey
city: Providence
country: United States
facility: Research Site
state: Rhode Island
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Clayton
country: Australia
facility: Research Site
city: Melbourne
country: Australia
facility: Research Site
city: Melbourne
country: Australia
facility: Research Site
city: Randwick
country: Australia
facility: Research Site
Study officials:
affiliation: Sponsor GmbH
name: MedImmune LLC
role: STUDY_DIRECTOR
References: