Advanced Solid Tumors
Conditions
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.
Interventions
BIOLOGICALMEDI5083 monotherapy
Dose-escalation MEDI5083 monotherapy followed by monotherapy with Durvalumab
BIOLOGICALMEID5083 with Durvalumab or Tremelimumab
Sequential Medi5083 with concurrent Durvalumab or Tremelimumab, and intermittent Medi5083 with concurrent Durvalumab
BIOLOGICALMedi5083 with Durvalumab and Docetaxel
Medi5083 with concurrent Durvalumab and Docetaxel randomized against Durvalumab and Docetaxel
Sponsors
MedImmune LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 101 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Adverse Events (AEs) as a measure of safety | From the time of consent through 120 days after last treatment | Safety Endpoint |
| Number of participants with Serious Adverse Events (SAEs) as a measure of safety | From the time of consent through 120 days after last treatment | Safety Endpoint |
| Number of participants with Dose Limiting Toxicities (DLTs) as a measure of safety | From the time of first dose through 28 days thereafter | Safety Endpoint |
| The Maximum Tolerated Dose (MTD) or Highest Protocol-Defined Dose | From the time of first dose through end of study (2 years after last subject enrolled or earlier at sponsor discretion) | Safety Endpoint |
| Discontinuation of investigational products due to toxicity | From the time of first dose through end of study (2 years after last subject enrolled or earlier at sponsor discretion) | Safety Endpoint |
| Clinically significant alterations in vital signs, laboratory parameters, physical examination, and electrocardiogram (ECG) results. | From the time of first dose through end of study (2 years after last subject enrolled or earlier at sponsor discretion) | Safety Endpoint |
| Antitumor activity endpoints OR, based on RECIST v1.1 | Part 3 | Safety Endpoint |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum MEDI5083 concentration levels | From the time of first dose through 57 days after first treatment | Pharmacokinetics (PK) |
| Duration of Response (DoR) | From the time of consent through end of study (2 years after last subject enrolled or earlier at sponsor discretion) | Clinical Activity Endpoint |
| Reduction in peripheral blood CD19+ B cells | From the time of first dose through 57 days after first treatment | Pharmacodynamics (PD) |
| Incidence of anti-drug antibody (ADA) responses to MEDI5083 | From the time of first dose through 2 years after last treatment | Immunogenicity |
| Objective Response Rate (ORR) | From the time of consent through end of study (2 years after last subject enrolled or earlier at sponsor discretion) | Clinical Activity Endpoint |
| Progression Free Survival (PFS) at 6 months (PFS-6) | From the time of first dose until 6 months after the last subject is dosed | Clinical Activity Endpoint |
| Overall Survival (OS) | From the time of consent through end of study (2 years after last subject enrolled or earlier at sponsor discretion) | Clinical Activity Endpoint |
| Disease Control Rate (DCR) | From the time of consent through end of study (2 years after last subject enrolled or earlier at sponsor discretion) | Clinical Activity Endpoint |
| Serum Durvalumab concentration levels collected over time | From the time of first dose through 29 days after first treatment | Pharmacokinetics (PK) |
| Incidence of anti-drug antibody (ADA) responses to Durvalumab | From the time of first dose through 2 years after last treatment | Immunogenicity |
| Incidence of anti-drug antibody (ADA) responses to tremelilumab | From the time of first dose through 2 years after last treatment | Immunogenicity |
| Serum tremelimumab concentration levels collected over time | From the time of first dose through 57 days after first treatment | Pharmacodynamics (PD) |
| PD of MEDI5083 alone and in combination with Durvalumab and tremelimumab | From the time of first dose through 57 days after first treatment | Pharmacodynamics (PD) |
| Safety and tolerability of MEDI5083 with durvalumamb and docetaxel and in subjects with IO relapsed/refractory 2/3L NSCLC | From the time of first dose through 57 days after first treatment | Safety |
Countries
Australia, United States
Outcome results
None listed