A Study to Evaluate MEDI5752 in Subjects With Advanced Solid Tumors
- Conditions
- Selected Advanced Solid Tumors
- Interventions
- Biological: MEDI5752Biological: Pembrolizumab
- Registration Number
- NCT03530397
- Lead Sponsor
- MedImmune LLC
- Brief Summary
The purpose of this study is to evaluate MEDI5752 and carboplatin and pemetrexed or paclitaxel or nab-paclitaxel in adult subjects with advanced solid tumors, when administered as a single agent or combined with chemotherapy.
- Detailed Description
This is a phase 1, first-time-in-human, multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety and tolerability, and efficacy, pharmacokinetics and Immunogenicity of MEDI5752 and carboplatin and pemetrexed or paclitaxel or nab-paclitaxel in adult subjects with advanced solid tumors, when administered as a single agent or combined with chemotherapy.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 401
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Arm A: MEDI5752 MEDI5752 MEDI5752 Arm B: MEDI5752 and chemotherapy Paclitaxel or Nab-Paclitaxel MEDI5752, pemetrexed, carboplatin and paclitaxel. Arm B: MEDI5752 and chemotherapy MEDI5752 MEDI5752, pemetrexed, carboplatin and paclitaxel. Arm B: MEDI5752 and chemotherapy Pemetrexed MEDI5752, pemetrexed, carboplatin and paclitaxel. Arm C: Pembrolizumab and chemotherapy Pembrolizumab pembrolizumab, pemetrexed, and carboplatin Arm B: MEDI5752 and chemotherapy Carboplatin MEDI5752, pemetrexed, carboplatin and paclitaxel. Arm C: Pembrolizumab and chemotherapy Carboplatin pembrolizumab, pemetrexed, and carboplatin Arm C: Pembrolizumab and chemotherapy Pemetrexed pembrolizumab, pemetrexed, and carboplatin
- Primary Outcome Measures
Name Time Method Preliminary anti-tumor activitiy of MEDI5752 (versus pembrolizumab, where applicable) using Objective Response based on RECIST v1.1 (Dose-expansion phase) From the first dose of study drug through the date of first documented progression, end of study, date of death, or two years after the last patient starts treatment, whichever should occur first The primary endpoint of antitumor activity include Objective Response and will be based on all post baseline disease assessments that occur prior to initiation of subsequent anticancer therapy.
The number of subjects experiencing abnormal laboratory evaluations (Dose-escalation phase) From the time of informed consent through 114 days following termination of treatment with investigational product The primary endpoint is as assessed as the number of subjects experiencing changes in laboratory parameters from baseline.
The number of subjects experiencing dose-limiting toxicities (DLTs) (Dose-escalation phase) Up to 21 days following the first dose The primary endpoint is as assessed by the number of subjects experiencing dose limiting toxicities (DLTs) as defined by the protocol.
The number of subjects experiencing treatment related adverse events (AEs) (Dose-escalation phase) From the time of informed consent through 114 days following termination of treatment with investigational product The primary endpoint is as assessed by the number of subjects experiencing adverse events (AEs) graded per NCI CTCAE v4.03
The number of subjects experiencing abnormal electrocardiograms (ECG) reported as Adverse Events (Dose-escalation phase) From the time of informed consent through 114 days following termination of treatment with investigational product The primary endpoint is as assessed by the the number of subjects experiencing clinically significant changes in ECG parameters from baseline.
The number of subjects experiencing changes from baseline in vital signs reported as adverse events (Dose-escalation phase) From the time of informed consent through 114 days following termination of treatment with investigational product The primary endpoint is as assessed by the number of subjects experiencing clinically significant changes in vital signs from baseline.
The number of subjects experiencing treatment related serious adverse events (SAEs) (Dose-escalation phase) From the time of informed consent through 114 days following termination of treatment with investigational product The primary endpoint is as assessed by the number of subjects with serious adverse events (SAEs) graded per NCI CTCAE v4.03.
- Secondary Outcome Measures
Name Time Method Ability of MEDI5752 to generate immune response in subjects with advanced solid tumors To be assessed at Day 1, 8, 15, 22, 29, 43, 64, 85, and 106 over the first 4 months of treatment and up to 114 days following end of treatment. The endpoints for the immunogenicity of MEDI5752 include the number of subjects who develop detectable anti-drug antibodies (ADAs)
Preliminary Antitumor Activity: Progression Free Survival From the first dose of study drug through the date of first documented progression, end of study, date of death, or two years after last subject starts treatment whichever should occur first The endpoints for assessment of antitumor activity include progression free survival (PFS) and is defined as the duration measured from the start of treatment with investigational product to the first documentation of disease progression or death due to any cause.
The number of subjects experiencing abnormal laboratory evaluations (Dose-expansion phase) From the time of informed consent through 114 days following termination of treatment with investigational product The secondary endpoint is as assessed by the number of subjects experiencing changes in laboratory parameters from baseline.
Pharmacokinetics of MEDI5752: AUC To be assessed at Day 1, 2, 3, 8, 15, 22, 29, 43, 64, 85, and 106 over the first 4 months of treatment and up to 114 days following end of treatment The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration. PK parameters that may be modeled on this data include area under the concentration-time curve (AUC)
Preliminary Antitumor Activity: Disease Control From the first dose of study drug through the date of first documented progression, end of study, date of death, or two years after last subject starts treatment whichever should occur first The endpoints for assessment of antitumor activity include disease control (DC) and is defined as CR, PR, or SD according to RECIST v1.1.
The number of subjects experiencing treatment related adverse events (AEs) (Dose-expansion phase) From the time of informed consent through 114 days following termination of treatment with investigational product The secondary endpoint is as assessed by the number of subjects experiencing adverse events (AEs) graded per NCI CTCAE v4.03
The number of subjects experiencing Changes from baseline in vital signs reported as adverse events (Dose-expansion phase) From the time of informed consent through 114 days following termination of treatment with investigational product The secondary endpoint is as assessed by the number of subjects experiencing clinically significant changes in vital signs from baseline.
Pharmacokinetics of MEDI5752: Cmax To be assessed at Day 1, 2, 3, 8, 15, 22, 29, 43, 64, 85, and 106 over the first 4 months of treatment and up to 114 days following end of treatment The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration. PK parameters that may be modeled on this data include maximum observed concentration (Cmax)
The number of subjects experiencing treatment related serious adverse events (SAEs) (Dose-expansion phase) From the time of informed consent through 114 days following termination of treatment with investigational product The secondary endpoint is as assessed by the number of subjects with serious adverse events (SAEs) graded per NCI CTCAE v4.03
Pharmacokinetics of MEDI5752: Clearance To be assessed at Day 1, 2, 3, 8, 15, 22, 29, 43, 64, 85, and 106 over the first 4 months of treatment and up to 114 days following end of treatment The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration. PK parameters that may be modeled on this data include clearance (CL)
Pharmacokinetics of MEDI5752: t 1/2 To be assessed at Day 1, 2, 3, 8, 15, 22, 29, 43, 64, 85, and 106 over the first 4 months of treatment and up to 114 days following end of treatment. The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration. PK parameters that may be modeled on this data include terminal phase half life (t 1/2)
PD-L1 Expression in subjects with advanced solid tumors To be assessed at baseline The endpoint for the PD-L1 expression will be determined by Immunohistochemistry characterization.
Preliminary Antitumor Activity: Duration of Response From the date of response through the date of first documented progression, end of study, date of death, or two years after last subject starts treatment whichever should occur first The endpoints for assessment of antitumor activity include duration of response (DoR) and is defined as the duration from the documentation of OR to the first documentation of disease progression or death due to any cause.
Preliminary Antitumor Activity: Overall Survival From the first dose of study drug through the end of study, or date of death, or two years after last subject starts treatment whichever should occur first The endpoints for assessment of antitumor activity include overall survival (OS) and is defined as the duration measured from the start of treatment with investigational product until death due to any cause.
The number of subjects experiencing abnormal ECGs reported as adverse events (Dose-expansion phase) From the time of informed consent through 14 days following termination of treatment with investigational product The secondary endpoint is as assessed by the number of subjects experiencing clinically significant changes in ECG parameters from baseline.
Trial Locations
- Locations (1)
Research Site
🇨🇳Taipei, Taiwan