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

Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03089645
• Other study ID #: D6840C00001
• Status: Completed
• Phase: Phase 1
• Start date: March 21, 2017
• Est. completion date: June 23, 2020

Study information

• Verified date: July 2020
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: June 23, 2020
• Est. primary completion date: June 23, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 101 Years

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumors

Intervention

Biological:
• MEDI5083 monotherapy
Dose-escalation MEDI5083 monotherapy followed by monotherapy with Durvalumab
• MEID5083 with Durvalumab or Tremelimumab
Sequential Medi5083 with concurrent Durvalumab or Tremelimumab, and intermittent Medi5083 with concurrent Durvalumab
• Medi5083 with Durvalumab and Docetaxel
Medi5083 with concurrent Durvalumab and Docetaxel randomized against Durvalumab and Docetaxel

Locations

Country	Name	City	State
Australia	Research Site	Clayton
Australia	Research Site	Melbourne
Australia	Research Site	Melbourne
Australia	Research Site	Randwick
United States	Research Site	Hackensack	New Jersey
United States	Research Site	Nashville	Tennessee
United States	Research Site	Providence	Rhode Island
United States	Research Site	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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)
Primary	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)
Primary	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)
Primary	Antitumor activity endpoints OR, based on RECIST v1.1	Safety Endpoint	Part 3
Secondary	Serum MEDI5083 concentration levels	Pharmacokinetics (PK)	From the time of first dose through 57 days after first treatment
Secondary	Reduction in peripheral blood CD19+ B cells	Pharmacodynamics (PD)	From the time of first dose through 57 days after first treatment
Secondary	Incidence of anti-drug antibody (ADA) responses to MEDI5083	Immunogenicity	From the time of first dose through 2 years after last treatment
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Serum Durvalumab concentration levels collected over time	Pharmacokinetics (PK)	From the time of first dose through 29 days after first treatment
Secondary	Incidence of anti-drug antibody (ADA) responses to Durvalumab	Immunogenicity	From the time of first dose through 2 years after last treatment
Secondary	Incidence of anti-drug antibody (ADA) responses to tremelilumab	Immunogenicity	From the time of first dose through 2 years after last treatment
Secondary	Serum tremelimumab concentration levels collected over time	Pharmacodynamics (PD)	From the time of first dose through 57 days after first treatment
Secondary	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
Secondary	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