Clinical trial NCT02261220: A Phase 1 Study of MEDI4736 in Combination With Tremelimumab in Subjects With Advanced Solid Tumors
Official title: A Phase I Study of MEDI4736 (Anti-PD-L1 Antibody) in Combination With Tremelimumab (Anti-CTLA-4 Antibody) in Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: advanced solid tumors
durvalumab
tremelimumab
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2014-10-10
Enrollment: 380
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a multicenter, open-label, dose-exploration and dose-expansion study to evaluate the safety, tolerability, antitumor activity, PK and immunogenicity of MEDI4736 in combination with tremelimumab in subjects with select advanced solid tumors.


Eligibility criteria: Inclusion Criteria:

* Male and female subjects
* 18 years and older
* Histologic confirmation of advanced solid tumors
* Subjects must have recurrent/metastatic disease and may have been previously treated in the recurrent/metastatic setting.

Exclusion Criteria:

* Any concurrent chemotherapy, immune-mediated therapy or biologic or hormonal therapy for cancer treatment
* Active or prior documented autoimmune disease within the past 2 years
* Current or prior use of immunosuppressive medication within 14 days with some exceptions.

Primary outcomes:
measure: Number of subjects reporting adverse events
timeFrame: Screening through 15 months after the last subject enters re-treatment
measure: Number of subjects reporting serious adverse events
timeFrame: Screening through 15 months after the last subject enters re-treatment
measure: Number of subjects experiencing a dose-limiting toxicity
timeFrame: First dose of study medication through 4 weeks after the first dose of study medication
measure: Change from Baseline in laboratory evaluations
timeFrame: Screening through 3 months after the last dose of study medication
measure: Change from Baseline in vital signs
timeFrame: Screening through 3 months after the last dose of study medication
measure: Change from Baseline in electrocardiogram evaluations
timeFrame: Screening through 3 months after the last dose of study medication
measure: Overall Response Rate in Select Tumor Types
timeFrame: First dose of study medication through 15 months after the last subject enters re-treatment
Secondary outcomes:
measure: Overall Response Rate
timeFrame: First dose of study medication through 15 months after the last subject enters re-treatment
measure: Disease Control Rate
timeFrame: First dose of study medication through 15 months after the last subject enters re-treatment
measure: Duration of Response
timeFrame: First dose of study medication through 15 months after the last subject enters re-treatment
measure: Progression-Free Survival
timeFrame: First dose of study medication through 15 months after the last subject enters re-treatment
measure: Overall Survival
timeFrame: First dose of study medication through 15 months after the last subject enters re-treatment
measure: Individual MEDI4736 concentrations
timeFrame: First dose of MEDI4736 through 3 months after the last dose of study medication
measure: Individual tremelimumab concentrations
timeFrame: First dose of tremelimumab through 3 months after the last dose of study medication
measure: MEDI4736 area under the concentration-curve
timeFrame: First dose of MEDI4736 through 3 months after the last dose of study medication
measure: Tremelimumab area under the concentration-curve
timeFrame: First dose of tremelimumab through 3 months after the last dose of study medication
measure: Number of subjects that develop detectable antidrug antibodies to MEDI4736
timeFrame: First dose of MEDI4736 through 3 months after the last dose of study medication
measure: Number of subjects that develop antidrug antibodies to tremelimumab
timeFrame: First dose of tremelimumab through 3 months after the last dose of study medication
Other outcomes:
measure: Change in Biomarkers
timeFrame: Screening through 3 months following the last dose of study medication
Locations:
city: Scottsdale
country: United States
facility: Research Site
state: Arizona
city: Duarte
country: United States
facility: Research Site
state: California
city: La Jolla
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Whittier
country: United States
facility: Research Site
state: California
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Miami Beach
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Iowa City
country: United States
facility: Research Site
state: Iowa
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Bronx
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Fairfax
country: United States
facility: Research Site
state: Virginia
city: Seattle
country: United States
facility: Research Site
state: Washington
city: London
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Angers Cedex 02
country: France
facility: Research Site
city: BESANCON Cedex
country: France
facility: Research Site
city: Bordeaux Cedex
country: France
facility: Research Site
city: Lyon
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Montpellier
country: France
facility: Research Site
city: Pierre Benite
country: France
facility: Research Site
city: Vandoeuvre les Nancy
country: France
facility: Research Site
city: Villejuif
country: France
facility: Research Site
city: Jena
country: Germany
facility: Research Site
city: Münster
country: Germany
facility: Research Site
city: Tübingen
country: Germany
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Kfar Saba
country: Israel
facility: Research Site
city: Tel-Aviv
country: Israel
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Gwangju
country: Korea, Republic of
facility: Research Site
city: Seongnam-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Tilburg
country: Netherlands
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Middlesborough
country: United Kingdom
facility: Research Site
city: Oxford
country: United Kingdom
facility: Research Site
city: Wirral
country: United Kingdom
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: MedImmune LLC
role: STUDY_DIRECTOR
References:
citation: Zhang Q, Luo J, Wu S, Si H, Gao C, Xu W, Abdullah SE, Higgs BW, Dennis PA, van der Heijden MS, Segal NH, Chaft JE, Hembrough T, Barrett JC, Hellmann MD. Prognostic and Predictive Impact of Circulating Tumor DNA in Patients with Advanced Cancers Treated with Immune Checkpoint Blockade. Cancer Discov. 2020 Dec;10(12):1842-1853. doi: 10.1158/2159-8290.CD-20-0047. Epub 2020 Aug 14.