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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Biological: MEDI5083 monotherapy
* Biological: MEID5083 with Durvalumab or Tremelimumab
* Biological: Medi5083 with Durvalumab and Docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years at the time of screening or age of consent according to local law Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 Histologically or cytologically confirmed metastatic or recurrent tumor types Subjects who have received prior immunotherapy may be eligible Subjects must have at least one measurable lesion Consent to provide archival tumor tissue and pre/on-treatment biopsies Adequate organ and marrow function Consent to use one highly effective method of contraception Exclusion Criteria: Receipt of any systemic anticancer therapy within 28 days prior to the first dose of MEDI5083 Concurrent enrollment in another clinical study Active/prior autoimmune of inflammatory disorders History of immunodeficiency, solid organ transplant, or tuberculosis Known allergy/hypersensitivity to drug or components Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression Current or prior use of immunosuppressive medication within 14 days prior to the first dose of MEDI5083

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 101 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1<br>MEDI5083 monotherapy followed by Durvalumab monotherapy in subjects with advanced solid tumors | Biological: MEDI5083 monotherapy<br>* Dose-escalation MEDI5083 monotherapy followed by monotherapy with Durvalumab<br>|
| Experimental: Part 2<br>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<br>* Sequential Medi5083 with concurrent Durvalumab or Tremelimumab, and intermittent Medi5083 with concurrent Durvalumab<br>|
| Experimental: Part 3<br>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<br>* Medi5083 with concurrent Durvalumab and Docetaxel randomized against Durvalumab and Docetaxel<br>|

What is the study measuring?
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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 |