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Trial record 1 of 1 for:    D8540C00002
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A Multiple Ascending Dose Study of MEDI7247 in Advanced or Metastatic Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03811652
Recruitment Status : Completed
First Posted : January 22, 2019
Last Update Posted : December 30, 2019
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

Tracking Information
First Submitted Date  ICMJE December 21, 2018
First Posted Date  ICMJE January 22, 2019
Last Update Posted Date December 30, 2019
Actual Study Start Date  ICMJE December 20, 2018
Actual Primary Completion Date December 10, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 17, 2019)
  • Occurrence of Adverse Events [ Time Frame: From time of informed consent through 90 days post end of treatment ]
    To assess the occurrence of adverse events
  • Occurrence of Serious Adverse Events [ Time Frame: From time of informed consent through 90 days post end of treatment ]
    To assess the occurrence of serious adverse events
  • Occurrence of Dose Limiting Toxicities [ Time Frame: During the evaluation period of 21 days post first dose ]
    To assess the occurrence of toxicities and abnormal laboratory results that may limit further dose administration
  • Number of patients with changes in laboratory parameters from baseline [ Time Frame: From time of informed consent through 90 days post end of treatment ]
    To assess serum chemistry, hematology, urinalysis and coagulation parameters
  • Number of patients with changes in vital signs parameters from baseline [ Time Frame: from time of informed consent through 21 days post last dose ]
    to assess changes in vital signs
  • Number of patients with changes in electrocardiogram results from baseline [ Time Frame: from time of informed consent through 21 days post last dose ]
    to assess changes in ECG
  • Percentage of patients with changes in laboratory parameters from baseline [ Time Frame: from time of informed consent through 90 days post end of treatment ]
    to assess changes in serum chemistry, hematology, urinalysis, and coagulation parameters
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 17, 2019)
  • MEDI7247 maximum observed concentration (Cmax) [ Time Frame: From first dose through 90 days post end of treatment ]
    To characterize MEDI7247 single agent Pharmacokinetics
  • MEDI7247 terminal half life (t1/2) [ Time Frame: From first dose through 90 days post end of treatment ]
    To characterize single agent MEDI7247 pharmacokinetics
  • MEDI7247 area under the concentration/time curve (AUC) [ Time Frame: from first dose through 90 days post end of treatment ]
    To characterize single agent MEDI7247 pharmacokinetics
  • MEDI7247 clearance [ Time Frame: from first dose through 90 days post end of treatment ]
    to characterize the single agent MEDI7247 pharmacokinetics
  • Number of subjects who develop anti-drug antibodies [ Time Frame: first dose through 90 days post end of treatment ]
    To characterize MEDI7247 immunogenicity
  • Best Overall Response [ Time Frame: From time of informed consent and up to 90 days post end of treatment ]
    To assess antitumor activity of MEDI7247
  • Objective Response Rate (ORR) [ Time Frame: From time of informed consent and up to 2 years after last subject in ]
    To assess antitumor activity of MEDI7247
  • Time to Response (TTR) [ Time Frame: From time of informed consent and up to 90 days post end of treatment ]
    To assess antitumor activity of MEDI7247
  • Duration of Response (DoR) [ Time Frame: From time of informed consent and up to 2 years after last subject in ]
    To assess antitumor activity of MEDI7247
  • Progression Free Survival (PFS) [ Time Frame: From time of informed consent and up to 2 years after last subject in ]
    To assess the antitumor activity of MEDI7247
  • Disease Control (DC) [ Time Frame: From time of informed consent and up to 2 years after last subject in ]
    To assess antitumor activity of MEDI7247
  • Overall Survival (OS) [ Time Frame: From time of informed consent and up to 2 years after last subject in ]
    To assess antitumor activity of MEDI7247
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Multiple Ascending Dose Study of MEDI7247 in Advanced or Metastatic Solid Tumors
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Non Small Cell Lung Cancer Squamous (NSCLC-Sq)
  • Head and Neck Squamous Cell Carcinoma (HNSCC)
  • Small Cell Lung Cancer (SCLC)
  • Pancreatic Ductal Adenocarcinoma (PDAC)
  • Colorectal Cancer (CRC)
  • Metastatic Castration-resistant Prostate Cancer (mCRPC)
Intervention  ICMJE Drug: MEDI7247
Subjects with advanced solid tumors will enroll into the respective arms to receive Medi7247 IV at prescribed dose and schedule
Study Arms  ICMJE
  • 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.
    Intervention: Drug: MEDI7247
  • 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.
    Intervention: Drug: MEDI7247
  • 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.
    Intervention: Drug: MEDI7247
  • 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.
    Intervention: Drug: MEDI7247
  • 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.
    Intervention: Drug: MEDI7247
  • 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
    Intervention: Drug: MEDI7247
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 30, 2019)
8
Original Estimated Enrollment  ICMJE
 (submitted: January 17, 2019)
336
Actual Study Completion Date  ICMJE December 10, 2019
Actual Primary Completion Date December 10, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 101 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries Australia,   France
 
Administrative Information
NCT Number  ICMJE NCT03811652
Other Study ID Numbers  ICMJE D8540C00002
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party MedImmune LLC
Study Sponsor  ICMJE MedImmune LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account MedImmune LLC
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP