A Phase 1 Study to Evaluate AMP-514

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Amplimmune
Sponsor:
Collaborator:
MedImmune LLC
Information provided by (Responsible Party):
Amplimmune
ClinicalTrials.gov Identifier:
NCT02013804
First received: December 12, 2013
Last updated: December 18, 2013
Last verified: December 2013
  Purpose

This is a multi-center, open-label, multi-dose, first-time-in-human study with a standard 3+3 dose-escalation phase in subjects with advanced solid malignancies.


Condition Intervention Phase
Advanced Solid Malignancies
Drug: AMP-514
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1, Multi-Center, Open-label, Multi-Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of AMP-514 in Subjects With Advanced Solid Malignancies

Resource links provided by NLM:


Further study details as provided by Amplimmune:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Pharmacokinetic profile of AMP-514 [ Time Frame: Through 90 days after the last dose of AMP-514 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Includes assessment of receptor occupancy, reduction in PD-1 expression levels, and increase in T cells producing effector cytokines and lytic markers


Estimated Enrollment: 24
Study Start Date: December 2013
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AMP-514
Escalating doses of AMP-514
Drug: AMP-514
AMP-514 will be administered by IV infusion every 21 days
Other Name: MEDI0680

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ≥18 years of age at time of study entry
  • Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act [HIPAA]) obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations
  • Life Expectancy of ≥ 12 weeks
  • Histologically- or cytologically-confirmed advanced solid tumor that is refractory to standard therapy or for which no standard therapy exists
  • At least 1 measurable lesion per RECIST 1.1; subjects whose only measurable lesion is a lymph node will be excluded
  • ECOG Performance Score of 0 or 1
  • Adequate organ and marrow function
  • Prior treatment toxicities must be ≤ Grade 1
  • Willingness to provide consent for biopsy samples
  • Females of childbearing and unsterilized males must use 2 methods of effective contraception from screening, and must agree to continue using such precautions for 90 days after the final dose of AMP-514

Exclusion Criteria:

  • Concurrent enrollment in another clinical study, unless it is an observational (non interventional) clinical study or the follow-up period of an interventional study
  • Receipt of any immunotherapy, BRAF inhibitor (in metastatic melanoma), or investigational anticancer therapy within 4 weeks prior to the first dose of AMP-514; in the case of monoclonal antibodies, 6 weeks prior to the first dose of AMP-514
  • Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
  • Any prior Grade ≥3 immune-related adverse event (irAE) while receiving immunotherapy or any unresolved irAE > Grade 1
  • Major surgery (as defined by the investigator) within 4 weeks prior to first dose of AMP-514 or still recovering from prior surgery
  • 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
  • Prior allogeneic or autologous bone marrow or organ transplantation that requires use of immunosuppressives
  • Unresolved toxicities from prior anticancer therapy, defined as having not resolved to National Cancer Institute's (NCI's) Common Terminology Criteria for Adverse Events (CTCAE) (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 AMP-514 may be included (eg, hearing loss) after consultation with the MedImmune medical monitor.
  • Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded
  • History of primary immunodeficiency
  • Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable. NOTE: Local treatment of isolated lesions for palliative intent is acceptable (eg, by local surgery or radiotherapy)
  • Current or prior use of immunosuppressive medication within 28 days before the first dose of AMP-514, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
  • Uncontrolled intercurrent illness
  • Symptomatic or untreated central nervous system metastases requiring concurrent treatment
  • Known history of tuberculosis
  • Subjects who are known to be human immunodeficiency virus positive
  • Subjects who are known to be hepatitis B or C positive
  • Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving AMP-514
  • Pregnant or breastfeeding women
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02013804

Locations
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Amanda Mundy    615-329-7274    amanda.mundy@scresearch.net   
Principal Investigator: Jeffrey Infante, MD         
Sponsors and Collaborators
Amplimmune
MedImmune LLC
Investigators
Study Director: Solomon Langermann, PhD Amplimmune
  More Information

No publications provided

Responsible Party: Amplimmune
ClinicalTrials.gov Identifier: NCT02013804     History of Changes
Other Study ID Numbers: AMP-514-01, MEDI0680
Study First Received: December 12, 2013
Last Updated: December 18, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Amplimmune:
Non-small cell lung cancer
Renal cell cancer
Colorectal cancer
Advanced malignant melanoma
Advanced cutaneous melanoma
Hepatocellular cancer
Squamous cell carcinoma of the head and neck
Gastroesophageal cancer
Triple negative breast cancer
Pancreatic adenocarcinoma
AMP-514
MEDI0680
Advanced solid tumors
PD-1
Anti PD-1
PD-L1
PD-L2

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on July 24, 2014