Clinical trial NCT03530397: 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.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Selected Advanced Solid Tumors
Keywords: Advanced solid tumors
MEDI5752
immuno-oncology
Cancer
PD-1/CTLA-4 Bispecific
PD-1
CTLA-4
Bispecific
Chemotherapy
Pemetrexed
Carboplatin
Pembrolizumab
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2018-05-21
Enrollment: 401
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: The number of subjects experiencing treatment related adverse events (AEs) (Dose-escalation phase)
timeFrame: From the time of informed consent through 114 days following termination of treatment with investigational product
measure: Preliminary anti-tumor activitiy of MEDI5752 (versus pembrolizumab, where applicable) using Objective Response based on RECIST v1.1 (Dose-expansion phase)
timeFrame: 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
measure: The number of subjects experiencing dose-limiting toxicities (DLTs) (Dose-escalation phase)
timeFrame: Up to 21 days following the first dose
measure: The number of subjects experiencing abnormal laboratory evaluations (Dose-escalation phase)
timeFrame: From the time of informed consent through 114 days following termination of treatment with investigational product
measure: The number of subjects experiencing changes from baseline in vital signs reported as adverse events (Dose-escalation phase)
timeFrame: From the time of informed consent through 114 days following termination of treatment with investigational product
measure: The number of subjects experiencing abnormal electrocardiograms (ECG) reported as Adverse Events (Dose-escalation phase)
timeFrame: From the time of informed consent through 114 days following termination of treatment with investigational product
measure: The number of subjects experiencing treatment related serious adverse events (SAEs) (Dose-escalation phase)
timeFrame: From the time of informed consent through 114 days following termination of treatment with investigational product
Secondary outcomes:
measure: Pharmacokinetics of MEDI5752: Cmax
timeFrame: 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
measure: Pharmacokinetics of MEDI5752: AUC
timeFrame: 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
measure: Pharmacokinetics of MEDI5752: Clearance
timeFrame: 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
measure: Pharmacokinetics of MEDI5752: t 1/2
timeFrame: 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.
measure: Ability of MEDI5752 to generate immune response in subjects with advanced solid tumors
timeFrame: 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.
measure: PD-L1 Expression in subjects with advanced solid tumors
timeFrame: To be assessed at baseline
measure: Preliminary Antitumor Activity: Duration of Response
timeFrame: 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
measure: Preliminary Antitumor Activity: Disease Control
timeFrame: 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
measure: Preliminary Antitumor Activity: Progression Free Survival
timeFrame: 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
measure: Preliminary Antitumor Activity: Overall Survival
timeFrame: 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
measure: The number of subjects experiencing treatment related adverse events (AEs) (Dose-expansion phase)
timeFrame: From the time of informed consent through 114 days following termination of treatment with investigational product
measure: The number of subjects experiencing abnormal laboratory evaluations (Dose-expansion phase)
timeFrame: From the time of informed consent through 114 days following termination of treatment with investigational product
measure: The number of subjects experiencing Changes from baseline in vital signs reported as adverse events (Dose-expansion phase)
timeFrame: From the time of informed consent through 114 days following termination of treatment with investigational product
measure: The number of subjects experiencing abnormal ECGs reported as adverse events (Dose-expansion phase)
timeFrame: From the time of informed consent through 14 days following termination of treatment with investigational product
measure: The number of subjects experiencing treatment related serious adverse events (SAEs) (Dose-expansion phase)
timeFrame: From the time of informed consent through 114 days following termination of treatment with investigational product
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: New York
country: United States
facility: Research Site
state: New York
city: Chapel Hill
country: United States
facility: Research Site
state: North Carolina
city: Providence
country: United States
facility: Research Site
state: Rhode Island
city: Chattanooga
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Fairfax
country: United States
facility: Research Site
state: Virginia
city: Melbourne
country: Australia
facility: Research Site
city: Melbourne
country: Australia
facility: Research Site
city: Randwick
country: Australia
facility: Research Site
city: Bordeaux Cedex
country: France
facility: Research Site
city: Lyon
country: France
facility: Research Site
city: Villejuif Cedex
country: France
facility: Research Site
city: Meldola
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Ravenna
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Cheongju-si
country: Korea, Republic of
facility: Research Site
city: Gyeonggi-do
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: A Coruna
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Majadahonda
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Deepa Subramaniam, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: