Description:
The purpose of this study is to evaluate MEDI5752 in adult subjects with advanced solid
tumors, when administered as a single agent or combined with chemotherapy.
Title
- Brief Title: A Study to Evaluate MEDI5752 in Subjects With Advanced Solid Tumors
- Official Title: A Phase 1, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability Pharmacokinetics Immunogenicity, and Antitumor Activity of MEDI5752 in Subjects With Advanced Solid Tumors.
Clinical Trial IDs
- ORG STUDY ID:
D7980C00001
- NCT ID:
NCT03530397
Conditions
- Selected Advanced Solid Tumors
Interventions
Drug | Synonyms | Arms |
---|
MEDI5752 | | Arm A: MEDI5752 |
Pemetrexed | | Arm B: MEDI5752 and chemotherapy |
Carboplatin | | Arm B: MEDI5752 and chemotherapy |
Pembrolizumab | | Arm C: Pembrolizumab and chemotherapy |
Purpose
The purpose of this study is to evaluate MEDI5752 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 in adult subjects with advanced solid tumors, when
administered as a single agent or combined with chemotherapy.
Trial Arms
Name | Type | Description | Interventions |
---|
Arm A: MEDI5752 | Experimental | MEDI5752 | |
Arm B: MEDI5752 and chemotherapy | Experimental | MEDI5752, pemetrexed and carboplatin. | - MEDI5752
- Pemetrexed
- Carboplatin
|
Arm C: Pembrolizumab and chemotherapy | Active Comparator | pembrolizumab, pemetrexed, and carboplatin | - Pemetrexed
- Carboplatin
- Pembrolizumab
|
Eligibility Criteria
Inclusion Criteria
1. Age ≥ 18 years at the time of screening
2. World Health Organization/Eastern Cooperative Oncology Group (ECOG) performance status
of 0 or 1 at enrollment
3. Life expectancy ≥ 12 weeks
4. Histologically or cytologically-confirmed advanced solid tumors
5. Subjects who have received prior anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy or any
concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy
for cancer treatment may be eligible to enter the study following a washout period as
applicable
6. Females of childbearing potential who are sexually active with a nonsterilized male
partner must use at least one highly effective method of contraception
7. Nonsterilized males who are sexually active with a female partner of childbearing
potential must use a male condom with spermicide where locally available from Day 1
and for 90 days after the final dose of investigational product. Males receiving
pemetrexed or carboplatin must use contraception during study treatment and up to 6
months thereafter.
8. Subjects must have at least one measurable lesion
9. Adequate organ and marrow function
10. Written informed consent and any locally required authorization
11. Subjects must provide tumor material as applicable
Exclusion Criteria
1. Involvement in the planning and/or conduct of the study (applies to both MedImmune
staff and/or staff at the study site)
2. Concurrent enrollment in another clinical study, unless it is an observational
clinical study or the follow-up period of an interventional study
3. For subjects who have received prior anti-PD-1, anti-PD-L1, or anti-CTLA-4:
1. Subjects must not have received anti-PD-1, anti-PD-L1, anti-CTLA-4 or any other
immunotherapy or immune-oncology (IO) agent within 21 days of commencing
treatment with investigational product.
2. Subject must not have experienced a toxicity that led to permanent
discontinuation of prior immunotherapy.
3. All AEs while receiving prior immunotherapy must have completely resolved or
resolved to Grade 1 prior to screening for this study.
4. Current or prior use of immunosuppressive medication within 14 days before the first
dose of investigational product is excluded.
5. Receipt of live attenuated vaccine within 30 days prior to the first dose of
investigational product.
6. Active or prior documented autoimmune or inflammatory disorders
7. History of active primary immunodeficiency:
8. History of organ transplant
9. Known allergy or reaction to any component of the planned study treatment.
10. Untreated CNS metastatic disease, leptomeningeal disease, or cord compression
11. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to
NCI CTCAE v4.03 Grade 0 or 1, or to levels dictated in the inclusion/exclusion
criteria
12. Major surgical procedure (as defined by the investigator) within 28 days prior to the
first dose of Investigational Product or still recovering from prior surgery
13. Female subjects who are pregnant or breastfeeding, as well as male or female subjects
of reproductive potential who are not willing to employ one highly effective method of
birth control
14. Uncontrolled intercurrent illness, that would limit compliance with study requirement,
substantially increase risk of incurring AEs or compromise the ability of the subject
to give written informed consent.
15. Any condition that, in the opinion of the investigator, would interfere with
evaluation of the investigational product or interpretation of the subject's safety or
study results
16. Judgment by the investigator that the subject is unsuitable to participate in the
study and the subject is unlikely to comply with study procedures, restrictions, and
requirements.
Maximum Eligible Age: | 120 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | The number of subjects experiencing treatment related adverse events (AEs) (Dose-escalation phase) |
Time Frame: | From the time of informed consent through 114 days following termination of treatment with investigational product |
Safety Issue: | |
Description: | The primary endpoint is as assessed by the number of subjects experiencing adverse events (AEs) graded per NCI CTCAE v4.03 |
Secondary Outcome Measures
Measure: | Pharmacokinetics of MEDI5752: Cmax |
Time Frame: | 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 |
Safety Issue: | |
Description: | 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) |
Measure: | Pharmacokinetics of MEDI5752: AUC |
Time Frame: | 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 |
Safety Issue: | |
Description: | 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) |
Measure: | Pharmacokinetics of MEDI5752: Clearance |
Time Frame: | 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 |
Safety Issue: | |
Description: | 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) |
Measure: | Pharmacokinetics of MEDI5752: t 1/2 |
Time Frame: | 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. |
Safety Issue: | |
Description: | 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) |
Measure: | Immunogenicity of MEDI5752 |
Time Frame: | 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. |
Safety Issue: | |
Description: | The endpoints for the immunogenicity of MEDI5752 include the number of subjects who develop detectable anti-drug antibodies (ADAs) |
Measure: | PD-L1 Expression in subjects with advanced solid tumors |
Time Frame: | To be assessed at at baseline |
Safety Issue: | |
Description: | The endpoint for the PD-L1 expression will be determined by Immunohistochemistry characterization. |
Measure: | Preliminary Antitumor Activity: Duration of Response |
Time Frame: | 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 |
Safety Issue: | |
Description: | 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. |
Measure: | Preliminary Antitumor Activity: Disease Control |
Time Frame: | 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 |
Safety Issue: | |
Description: | The endpoints for assessment of antitumor activity include disease control (DC) and is defined as CR, PR, or SD according to RECIST v1.1. |
Measure: | Preliminary Antitumor Activity: Progression Free Survival |
Time Frame: | 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 |
Safety Issue: | |
Description: | 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. |
Measure: | Preliminary Antitumor Activity: Overall Survival |
Time Frame: | 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 |
Safety Issue: | |
Description: | 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. |
Measure: | The number of subjects experiencing treatment related adverse events (AEs) (Dose-expansion phase) |
Time Frame: | From the time of informed consent through 114 days following termination of treatment with investigational product |
Safety Issue: | |
Description: | The secondary endpoint is as assessed by the number of subjects experiencing adverse events (AEs) graded per NCI CTCAE v4.03 |
Measure: | The number of subjects experiencing abnormal laboratory evaluations (Dose-expansion phase) |
Time Frame: | From the time of informed consent through 114 days following termination of treatment with investigational product |
Safety Issue: | |
Description: | The secondary endpoint is as assessed by the number of subjects experiencing changes in laboratory parameters from baseline. |
Measure: | The number of subjects experiencing Changes from baseline in vital signs reported as adverse events (Dose-expansion phase) |
Time Frame: | From the time of informed consent through 114 days following termination of treatment with investigational product |
Safety Issue: | |
Description: | The secondary endpoint is as assessed by the number of subjects experiencing clinically significant changes in vital signs from baseline. |
Measure: | The number of subjects experiencing abnormal ECGs reported as adverse events (Dose-expansion phase) |
Time Frame: | From the time of informed consent through 14 days following termination of treatment with investigational product |
Safety Issue: | |
Description: | The secondary endpoint is as assessed by the number of subjects experiencing clinically significant changes in ECG parameters from baseline. |
Measure: | The number of subjects experiencing treatment related serious adverse events (SAEs) (Dose-expansion phase) |
Time Frame: | From the time of informed consent through 114 days following termination of treatment with investigational product |
Safety Issue: | |
Description: | The secondary endpoint is as assessed by the number of subjects with serious adverse events (SAEs) graded per NCI CTCAE v4.03 |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | MedImmune LLC |
Trial Keywords
- Advanced solid tumors
- MEDI5752
- immuno-oncology
- Cancer
- PD-1/CTLA-4 Bispecific
- PD-1
- CTLA-4
- Bispecific
- Chemotherapy
- Pemetrexed
- Carboplatin
- Pembrolizumab
Last Updated
September 1, 2021