A Phase 1/2 Study to Evaluate MEDI4736

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by MedImmune LLC
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT01693562
First received: September 14, 2012
Last updated: September 16, 2014
Last verified: September 2014
  Purpose

This is a multicenter, open-label, first-time-in-human study with a standard 3+3 dose-escalation phase in subjects with advanced solid tumors followed by an expansion phase in patients with advanced solid tumors.


Condition Intervention Phase
Advanced Solid Tumors
Drug: MEDI4736
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI4736 in Subjects With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • Number of participants experiencing dose-limiting toxicities, adverse events (AEs), serious adverse events (SAEs). [ Time Frame: 90 days after the last dose of MEDI4736 ] [ Designated as safety issue: Yes ]

    MTD or OBD will be determined by the number of participants experiencing dose-limiting toxicities.

    Safety profile will be assessed through number of participants experiencing adverse events (AEs), serious adverse events (SAEs), laboratory evaluations, vital signs, and physical examinations.


  • Anti-tumor efficacy (dose expansion subjects) [ Time Frame: Until end of study ] [ Designated as safety issue: No ]
    Evaluate the objective response rate in subjects with non-squamous NSCLC who have received 2 or more prior lines of therapy and subjects with squamous NSCLC who have received 1 prior lines of therapy and 2 or more prior lines of therapy


Secondary Outcome Measures:
  • Area under the concentration time curve, maximum concentration, clearance, half-life after administration of MEDI4736. [ Time Frame: Up to 90 days after the last dose of MEDI4736 ] [ Designated as safety issue: No ]
    If data allow, noncompartmental PK parameters (AUC, Cmax, CL, t½) will be estimated.

  • Number and percentage of subjects who develop detectable anti-drug antibodies (ADAs). [ Time Frame: Up to 6 months after the last dose of MEDI4736. ] [ Designated as safety issue: Yes ]
    The immunogenic potential of MEDI4736 will be assessed by summarizing the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs).

  • Objective response rate (ORR) [ Time Frame: Until end of study ] [ Designated as safety issue: No ]
    The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR

  • Disease control rate (DCR) [ Time Frame: Until end of study ] [ Designated as safety issue: No ]

    The DCR is defined as the proportion of subjects with CR, PR, or SD (subjects achieving SD will be included in the DCR if they maintain SD for

    ≥ 12 weeks)


  • Duration of response (DR) [ Time Frame: Until end of study ] [ Designated as safety issue: No ]
    Duration of response will be defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.

  • Progression-free survival (PFS) [ Time Frame: Until end of study ] [ Designated as safety issue: No ]
    Progression-free survival is the time interval from the start of treatment with MEDI4736 until the documentation of confirmed immune-related disease progression or death due to any cause, whichever occurs first.

  • Overall survival (OS) [ Time Frame: From first dose of study drug until death or up to 2 years ] [ Designated as safety issue: No ]
    Overall survival will be determined as the time from the start of treatment with MEDI4736 until death.


Estimated Enrollment: 950
Study Start Date: August 2012
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MEDI4736 Q2W
Evaluate MEDI4736 given every 2 weeks
Drug: MEDI4736
MEDI4736 will be administered by IV infusion every 14 or 21 days.
Experimental: MEDI4736 Q3W
Evaluate MEDI4736 given every 3 weeks
Drug: MEDI4736
MEDI4736 will be administered by IV infusion every 14 or 21 days.
Experimental: MEDI4736 Dose Expansion
At least 16 different types of solid tumors will be evaluated in the expansion phase
Drug: MEDI4736
MEDI4736 will be administered by IV infusion every 14 or 21 days.

Detailed Description:

A dose-escalation and dose-expansion study of MEDI4736 (a monoclonal antibody that targets programmed cell death-1 ligand 1 (PD-L1)) will evaluate the safety, tolerability, PK, IM, and antitumor activity of MEDI4637 in adult patients with solid tumors.

  Eligibility

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

Inclusion Criteria:

Age 18 or older. In the dose-escalation phase: histologically- or cytologically- confirmed advanced solid tumor that is refractory to standard therapy and for which no standard therapy exists.

  • In the dose-expansion phase: histologically- or cytologically- confirmed advanced solid tumor where if an approved first-line therapy is available, subjects must have failed, be intolerant to, be ineligible for, or have refused treatment.
  • Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.
  • Adequate organ and marrow function.
  • Subjects must have at least 1 measurable lesion.
  • Available archived tumor tissue sample.
  • Willingness to provide consent for biopsy samples (dose-expansion only)

Exclusion Criteria:

  • Any prior Grade ≥ 3 irAE while receiving immunotherapy
  • Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
  • Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment.
  • Active or prior documented autoimmune disease within the past 2 years
  • History of primary immunodeficiency
  • History of organ transplant that requires use of immunosuppressives
  • Symptomatic or untreated central nervous system (CNS) metastases requiring concurrent treatment
  • Other invasive malignancy within 2 years
  • Women who are pregnant or lactating
  • Uncontrolled intercurrent illness
  • Known history of tuberculosis
  • Known to be human immunodeficiency virus (HIV) positive
  • Known to be Hepatitis B or C positive (excpet HCC patients)
  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: NCT01693562

Contacts
Contact: Roxanne Akhavain 301-398-0000 ClinicalTrialEnquiries@Medimmune.com

  Show 39 Study Locations
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: Dominic Lai, MD MedImmune LLC
  More Information

No publications provided

Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT01693562     History of Changes
Other Study ID Numbers: CD-ON-MEDI4736-1108
Study First Received: September 14, 2012
Last Updated: September 16, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by MedImmune LLC:
Advanced solid tumors
Advanced Malignant Melanoma
Non-small Cell Lung Cancer
Advanced Cutaneous Melanoma
Uveal Melanoma
Hepatocellular Carcinoma
Squamous Cell Carcinoma of the Head and Neck
Gastroesophageal Cancer
Triple Negative Breast Cancer
Pancreatic Adenocarcinoma
Small Cell Lung Cancer
Bladder Cancer
Ovarian Cancer
Glioblastoma Multiforme
Soft Tissue Sarcoma
Nasopharyngeal Carcinoma
Human Papilloma Virus Positive Cancer
MSI High Cancer
MEDI4736

ClinicalTrials.gov processed this record on September 22, 2014