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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03811652




Registration number
NCT03811652
Ethics application status
Date submitted
21/12/2018
Date registered
21/01/2019
Date last updated
8/07/2019

Titles & IDs
Public title
A Multiple Ascending Dose Study of MEDI7247 in Advanced or Metastatic Solid Tumors
Scientific title
A Phase 1/1b Multicenter, Open-label, Dose-escalation, and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI7247 in Patients With Advanced or Metastatic Disease in Selected Solid Tumors
Secondary ID [1] 0 0
D8540C00002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non Small Cell Lung Cancer Squamous (NSCLC-Sq) 0 0
Head and Neck Squamous Cell Carcinoma (HNSCC) 0 0
Small Cell Lung Cancer (SCLC) 0 0
Pancreatic Ductal Adenocarcinoma (PDAC) 0 0
Colorectal Cancer (CRC) 0 0
Metastatic Castration-resistant Prostate Cancer (mCRPC) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell
Cancer 0 0 0 0
Prostate
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MEDI7247

Experimental: NSCLC-Sq/HNSCC - Patients with advanced or metastatic NSCLC-Sq or HNSCC who have recurrence after, or are refractory or intolerant to standard therapy, including at least one prior standard of care regimen (platinum-based for HNSCC). PDL-1 positive patients should have received previous PD-1 or PD-L1 inhibitor where available.

Experimental: Small Cell Lung Cancer - Patients with advanced SCLC who have recurrence after, or are refractory or intolerant to standard therapy, including at least one prior standard of care regimen.

Experimental: Colorectal Cancer - Patients with metastatic adenocarcinoma of the colon or rectum who have received and have progressed, or have documented intolerance, on prior thymidylate synthase inhibitor (eg, 5-fluorouracil (5-FU), capecitabine, raltitrexed, tegafur-uracil (UFT), irinotecan, and oxaliplatin for metastatic disease. If patients progress within 6 months of their last dose of adjuvant therapy this should be considered as a line of therapy in the metastatic setting. Patients with known RAS wildtype tumors must have received and progressed, or have documented intolerance, on anti-EGFR antibody. Patients with microsatellite instability-high or deficient mismatch repair tumors, must have received and progressed, or have documented intolerance on a PD-1 inhibitor, or PD-1 inhibitor plus cytotoxic T-lymphocyte antigen-4 inhibitor treatment where available.

Experimental: Pancreatic Ductal Adenocarcinoma - Patients with unresectable, locally advanced or metastatic PDAC who have recurrence after, or are refractory or intolerant to standard therapy, including at least one prior line of treatment.

Experimental: Metastatic Castration-Resistant Prostate Cancer - Patients with mCRPC who have received prior treatment with abiraterone or enzalutamide, with or without a prior taxane-based chemotherapy in the mCRPC setting.

Experimental: Other advanced/metastatic target expressing solid tumors - Patients with advanced or metastatic solid tumors not defined by other treatment arms who have positive expression of the protein target and have exhausted all approved therapies


Treatment: Drugs: MEDI7247
Subjects with advanced solid tumors will enroll into the respective arms to receive Medi7247 IV at prescribed dose and schedule

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Occurrence of Adverse Events - To assess the occurrence of adverse events
Timepoint [1] 0 0
From time of informed consent through 90 days post end of treatment
Primary outcome [2] 0 0
Occurrence of Serious Adverse Events - To assess the occurrence of serious adverse events
Timepoint [2] 0 0
From time of informed consent through 90 days post end of treatment
Primary outcome [3] 0 0
Occurrence of Dose Limiting Toxicities - To assess the occurrence of toxicities and abnormal laboratory results that may limit further dose administration
Timepoint [3] 0 0
During the evaluation period of 21 days post first dose
Primary outcome [4] 0 0
Number of patients with changes in laboratory parameters from baseline - To assess serum chemistry, hematology, urinalysis and coagulation parameters
Timepoint [4] 0 0
From time of informed consent through 90 days post end of treatment
Primary outcome [5] 0 0
Number of patients with changes in vital signs parameters from baseline - to assess changes in vital signs
Timepoint [5] 0 0
from time of informed consent through 21 days post last dose
Primary outcome [6] 0 0
Number of patients with changes in electrocardiogram results from baseline - to assess changes in ECG
Timepoint [6] 0 0
from time of informed consent through 21 days post last dose
Primary outcome [7] 0 0
Percentage of patients with changes in laboratory parameters from baseline - to assess changes in serum chemistry, hematology, urinalysis, and coagulation parameters
Timepoint [7] 0 0
from time of informed consent through 90 days post end of treatment
Secondary outcome [1] 0 0
MEDI7247 maximum observed concentration (Cmax) - To characterize MEDI7247 single agent Pharmacokinetics
Timepoint [1] 0 0
From first dose through 90 days post end of treatment
Secondary outcome [2] 0 0
MEDI7247 terminal half life (t1/2) - To characterize single agent MEDI7247 pharmacokinetics
Timepoint [2] 0 0
From first dose through 90 days post end of treatment
Secondary outcome [3] 0 0
MEDI7247 area under the concentration/time curve (AUC) - To characterize single agent MEDI7247 pharmacokinetics
Timepoint [3] 0 0
from first dose through 90 days post end of treatment
Secondary outcome [4] 0 0
MEDI7247 clearance - to characterize the single agent MEDI7247 pharmacokinetics
Timepoint [4] 0 0
from first dose through 90 days post end of treatment
Secondary outcome [5] 0 0
Number of subjects who develop anti-drug antibodies - To characterize MEDI7247 immunogenicity
Timepoint [5] 0 0
first dose through 90 days post end of treatment
Secondary outcome [6] 0 0
Best Overall Response - To assess antitumor activity of MEDI7247
Timepoint [6] 0 0
From time of informed consent and up to 90 days post end of treatment
Secondary outcome [7] 0 0
Objective Response Rate (ORR) - To assess antitumor activity of MEDI7247
Timepoint [7] 0 0
From time of informed consent and up to 2 years after last subject in
Secondary outcome [8] 0 0
Time to Response (TTR) - To assess antitumor activity of MEDI7247
Timepoint [8] 0 0
From time of informed consent and up to 90 days post end of treatment
Secondary outcome [9] 0 0
Duration of Response (DoR) - To assess antitumor activity of MEDI7247
Timepoint [9] 0 0
From time of informed consent and up to 2 years after last subject in
Secondary outcome [10] 0 0
Progression Free Survival (PFS) - To assess the antitumor activity of MEDI7247
Timepoint [10] 0 0
From time of informed consent and up to 2 years after last subject in
Secondary outcome [11] 0 0
Disease Control (DC) - To assess antitumor activity of MEDI7247
Timepoint [11] 0 0
From time of informed consent and up to 2 years after last subject in
Secondary outcome [12] 0 0
Overall Survival (OS) - To assess antitumor activity of MEDI7247
Timepoint [12] 0 0
From time of informed consent and up to 2 years after last subject in

Eligibility
Key inclusion criteria
1. Confirmed diagnosis of advanced or metastatic select solid tumors and either
progression on or documented intolerance to standard therapies

2. Age = 18 years at the time of screening.

3. Written informed consent and any locally required authorization

4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

5. At least 1 measurable target lesion by CT or MRI per RECIST Version 1.1 (excluding
mCRPC)

6. Adequate Liver Function: Aspartate Aminotransferase (AST) and Alanine Aminotransferase
(ALT) = 2.5 × ULN (upper limit normal), Albumin > 3 g/dL, and serum total bilirubin
(TBL) = 1.5 × ULN; (unless bilirubin rise is due to Gilbert's syndrome, hepatic
metastases or of non-hepatic origin, in which case TBL = 3 × ULN is allowed)

7. Creatinine Clearance (CrCL) = 40 mL/min

8. Adequate Hematopoesis: Absolute Neutrophil Count (ANC) = 1,500/µL, Platelets =
100,000/µL, and Hgb = 9 g/dL unassisted by transfusion or growth factor within 14 days
of screening

9. Provision of archival or fresh tumor tissue at screening

10. Female patients of childbearing potential who are sexually active with a nonsterilized
male partner must use at least one highly effective method of contraception, and must
agree to continue using such precautions for 90 days after the last dose of
investigational product.

11. Nonsterilized male patients who are sexually active with a female partner of
childbearing potential must use a male condom plus spermicide from 7 days
post-screening and for 90 days after receipt of the last dose of investigational
product.
Minimum age
18 Years
Maximum age
101 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Active central nervous system (CNS) metastases, unless adequately treated and patients
have neurologically returned to baseline (except for residual signs or symptoms
related to the CNS treatment) and prednisolone 10 mg or less for more than 2 weeks
prior to enrollment. For SCLC, a brain MRI scan that was conducted = 28 days from Day
1 is required.

2. Residual toxicity from prior anticancer therapy not resolved to NCI CTCAE v4.03 Grade
1, with the exception of alopecia/vitiligo at the time of first dose of
investigational product. For patients previously receiving immunotherapy, toxicities
that are unlikely to recover to Grade 1.

3. Royal Marsden Hospital (RMH) prognostic score 2 and 3 at baseline.

4. Treatment with anticancer therapy including chemotherapy, radiation therapy,
immunotherapy, biologic, or any investigational therapy within 21 days, or prior
palliative radiotherapy within 2 weeks of the first dose of investigational product.

5 Prior treatment with other Pyrrolobenzodiazepine-Antibody Drug Conjugates.

6 History of previous malignancies (except for locally curable cancers) unless a complete
remission was achieved at least 3 years prior to study entry AND no additional therapy is
required during the study period (except adjuvant hormonal therapy and bisphosphonate).

7. Failure to recover from major surgery or significant traumatic injury within 21 days of
first dose of study treatment.

8 History of hepatic sinusoidal obstruction syndrome, also called veno-occlusive disease 9.
History of capillary leak syndrome. 10 Blood transfusion within 14 days of study entry
except when needed for disease related anemia.

11. New York Heart Association classes III-IV congestive heart failure or serious cardiac
arrhythmia requiring treatment, history of myocardial infarction, unstable angina, vascular
stent, or coronary artery bypass graft within 6 months of the first dose of investigational
product. 12. Active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or
hepatitis C virus (HCV) infections at the time of screening.

13. Current severe active systemic disease including active concurrent malignancy 14.
Pregnancy and/or breastfeeding at time of screening 15. Concurrent enrollment in anther
clinical study involving an investigational treatment that is not an extension of another
MedImmune study with the same investigational product.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Heidelberg
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
North Carolina
Country [2] 0 0
United States of America
State/province [2] 0 0
Tennessee
Country [3] 0 0
Canada
State/province [3] 0 0
CA
Country [4] 0 0
France
State/province [4] 0 0
Villejuif

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
MedImmune LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
To assess safety and tolerability, describe the dose-limiting toxicities, assess the
preliminary antitumor activity, determine the maximum tolerated dose (MTD) or the highest
protocol-defined dose (maximum administered dose) in the absence of establishing the MTD, and
a recommended dose for further evaluation of MEDI7247 in patients with selected advanced or
metastatic solid tumor malignancies that have received at least 1 prior line of treatment.
Trial website
https://clinicaltrials.gov/show/NCT03811652
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
AstraZeneca Clinical Study Information Center
Address 0 0
Country 0 0
Phone 0 0
1-877-240-9479
Fax 0 0
Email 0 0
information.center@astrazeneca.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03811652