A Phase 1 Study to Evaluate MEDI4736 - Full Text View

Purpose

This is a multicenter, open-label, first-time-in-human study with a standard 3+3 dose-escalation phase in subjects with advanced malignant melanoma, renal cell carcinoma, non-small cell lung cancer, or colorectal cancer followed by an expansion phase in subjects with advanced malignant melanoma, non-small cell lung cancer, or colorectal cancer.

Condition	Intervention	Phase
Advanced Malignant Melanoma Renal Cell Carcinoma Non-small Cell Lung Cancer Colorectal Cancer	Drug: MEDI4736	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 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI4736 in Subjects With Advanced Solid Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer Lung Cancer Melanoma

U.S. FDA Resources

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.

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).
Immune-related objective response rate (ORR) [ Time Frame: 84 days ] [ Designated as safety issue: No ]
Immune-related disease control rate (DCR) [ Time Frame: 84 days ] [ Designated as safety issue: No ]
Immune-related duration of response (DR) [ Time Frame: From first documented response up to 2 years ] [ Designated as safety issue: No ]
Immune-related progression-free survival (PFS) [ Time Frame: From documented response up to 2 years ] [ Designated as safety issue: No ]
Overall survival (OS) [ Time Frame: From first dose of study drug until death or up to 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	110
Study Start Date:	September 2012
Estimated Study Completion Date:	October 2014
Estimated Primary Completion Date:	July 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: MEDI4736 Q2W	Drug: MEDI4736 MEDI4736 will be administered by IV infusion every 14 or 21 days.
Experimental: MEDI4736 Q3W	Drug: MEDI4736 MEDI4736 will be administered by IV infusion every 14 or 21 days.
Experimental: MEDI4736 Dose Expansion	Drug: MEDI4736 MEDI4736 will be administered by IV infusion every 14 or 21 days.

Eligibility

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

Criteria

Inclusion Criteria:

In the dose-escalation phase: histologically- or cytologically- confirmed advanced malignant melanoma, renal cell carcinoma, non-small cell lung cancer, or colorectal cancer that is refractory to standard therapy and for which no standard therapy exists.
In the dose-expansion phase: histologically- or cytologically- confirmed advanced malignant melanoma, colorectal cancer, or non-small cell lung cancer that is refractory to standard therapy and for which no standard therapy exists.
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 .

Exclusion Criteria:

Any prior Grade ≥ 3 irAE while receiving immunotherapy
Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
Active or prior documented autoimmune disease within the past 2 years
History of primary immunodeficiency
Symptomatic or untreated central nervous system (CNS) metastases requiring concurrent treatment
Women who are pregnant or lactating
Uncontrolled intercurrent illness
Known history of tuberculosis
Known to be human immunodeficiency virus (HIV) positive
Hepatitis A, B or C infection

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01693562

Contacts

Contact: Roxanne Akhavain

301-398-0000

clinicaltrialenquiries@medimmune.com

Locations

United States, Florida
Research Site	Recruiting
Miami Beach, Florida, United States
Research Site	Recruiting
Tampa, Florida, United States
United States, Georgia
Research Site	Recruiting
Augusta, Georgia, United States
United States, New York
Research Site	Recruiting
New York, New York, United States

Sponsors and Collaborators

MedImmune LLC

Investigators

Study Director:

Ramy Ibrahim, 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:	January 2, 2013
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board

Keywords provided by MedImmune LLC:

Advanced malignant melanoma
Renal cell carcinoma
Non-small cell lung cancer
Colorectal cancer

MEDI4736
Advanced solid tumors
B7-H1

Additional relevant MeSH terms:

Carcinoma
Carcinoma, Non-Small-Cell Lung
Carcinoma, Renal Cell
Colorectal Neoplasms
Lung Neoplasms
Melanoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases

Respiratory Tract Diseases
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases

ClinicalTrials.gov processed this record on May 23, 2013