A Phase 1 Multicenter Open-label Study to Evaluate the Safety Tolerability and PK of MEDI0680 (AMP-514) in Subjects With Advanced Malignancies

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. Identifier: NCT02013804
Recruitment Status : Completed
First Posted : December 17, 2013
Last Update Posted : October 6, 2017
Information provided by (Responsible Party):
MedImmune LLC

December 12, 2013
December 17, 2013
October 6, 2017
December 19, 2013
May 18, 2017   (Final data collection date for primary outcome measure)
Safety and Tolerability; define Maximum Tolerated dose [ Time Frame: 1 year ]
The primary objectives are to assess the safety and tolerability of multiple doses of MEDI0680 (AMP-514) and define the maximum tolerated dose (MTD) or highest protocol-defined dose of MEDI0680 (AMP-514) in the absence of exceeding the MTD.
Number of subjects experiencing dose-limiting toxicities (DLTs), adverse events (AEs), serious adverse events (SAEs) [ Time Frame: Through 90 days after last dose of AMP-514 ]
Maximum tolerated dose (MTD) or optimal biological dose (OBD) will be determined by the number of subjects experiencing DLTs. Safety profile will be assessed through the number of subjects experiencing AEs, SAEs, abnormal laboratory evaluations, vital signs, and physical examinations.
Complete list of historical versions of study NCT02013804 on Archive Site
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  • Pharmacokinetic profile of AMP-514 [ Time Frame: Through 90 days after the last dose of AMP-514 ]
    AMP-514 concentrations in serum and PK parameters including peak concentration, area under the concentration-time curve, clearance, and half-life.
  • Assess preliminary antitumor activity of AMP-514 [ Time Frame: Approximately every 3 months through 12 months following last cycle of AMP-514 ]
    Disease status evaluated via RECIST 1.1.
  • Evaluate pharmacodynamic effects of AMP-514 on its target receptor, PD-1, as well as effects on immune system function [ Time Frame: Approximately every 3 months through 12 months following last cycle of AMP-514 ]
    Includes assessment of receptor occupancy, reduction in PD-1 expression levels, and increase in T cells producing effector cytokines and lytic markers
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A Phase 1 Multicenter Open-label Study to Evaluate the Safety Tolerability and PK of MEDI0680 (AMP-514) in Subjects With Advanced Malignancies
A Phase 1, Multicenter, Open-label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI0680 (AMP-514) in Subjects With Advanced Malignancies
This is a multicenter, open label, first-in-human dose-escalation study of MEDI0680 (AMP-514) to evaluate the safety, tolerability, PK, immunogenicity (IM), and antitumor activity in adult subjects with solid tumors.
Not Provided
Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Advanced Malignancies
Drug: MEDI0680 (AMP-514)
Study has planned dose escalation cohorts
Experimental: Dose arms
Dose Escalation
Intervention: Drug: MEDI0680 (AMP-514)
Borch TH, Donia M, Andersen MH, Svane IM. Reorienting the immune system in the treatment of cancer by using anti-PD-1 and anti-PD-L1 antibodies. Drug Discov Today. 2015 Sep;20(9):1127-34. doi: 10.1016/j.drudis.2015.07.003. Epub 2015 Jul 17. Review.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
May 18, 2017
May 18, 2017   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. At least 18 years of age at time of study entry
  2. Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act [HIPAA] in the USA) obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations
  3. Histologically- or cytologically-confirmed melanoma or clear-cell RCC that are refractory to standard therapy or for which no standard therapy exists

    1. Subjects must have failed, be intolerant to, or be ineligible for any potentially curative approved treatment, irrespective of line of therapy
    2. No more than 3 prior lines of therapy
  4. At least 1 measurable lesion per RECIST v1.1; subjects whose only measurable lesion is a lymph node will be excluded
  5. Eastern Cooperative Oncology Group performance score of 0 or 1
  6. For all tumor types, adequate organ and marrow function, as defined below:

    1. Hemoglobin ³ 9.0 g/dL within first 2 weeks prior to first dose of MEDI0680 (AMP-514)
    2. Absolute neutrophil count (ANC) ³ 1.5 × 109/L (1,500/mm3)
    3. Platelet count ³ 100 × 109/L (100,000/mm3)
    4. Total bilirubin ≤ 1.5 × ULN except subjects with documented Gilbert's syndrome (> 3 × ULN) or liver metastasis, who must have a baseline total bilirubin ≤ 3.0 mg/
    5. Alanine aminotransferase and AST ≤ 2.5 × ULN; for subjects with hepatic metastases, ALT and AST ≤ 5 × ULN
    6. Serum creatinine ≤ 1.5 × ULN OR calculated creatinine clearance (CrCl) or 24-hour urine CrCl ≥ 50 mL/minute ▪ Cockcroft-Gault formula will be used to calculate CrCl; 24-hour urine CrCl will be derived using the measured creatinine clearance formula
  7. Prior treatment toxicities must be ≤ Grade 1

Exclusion Criteria:

  1. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study
  2. Receipt of any BRAF inhibitor (in metastatic melanoma), or investigational anticancer therapy within 4 weeks prior to the first dose of MEDI0680 (AMP-514)
  3. Prior exposure to immunotherapy, such as, but not limited to, other anti-CTLA-4, anti-PD-1, or anti-PD-L1 antibodies, excluding therapeutic cancer vaccines
  4. Major surgery (as defined by the investigator) within 4 weeks prior to first dose of MEDI0680 (AMP-514) or still recovering from prior surgery
  5. Other invasive malignancy within 2 years except for noninvasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured
  6. Prior allogeneic or autologous bone marrow or organ transplantation that requires use of immunosuppressives
  7. 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 with the exception of alopecia. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by MEDI0680 (AMP-514) may be included (eg, hearing loss) after consultation with the MedImmune medical monitor
  8. Active or prior documented autoimmune disease within the past 2 years
Sexes Eligible for Study: All
18 Years to 99 Years   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
United States
D6020C00002 (AMP-514-01) ( Other Identifier: MedImmune )
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MedImmune LLC
MedImmune LLC
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MedImmune LLC
September 2017

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