Durvalumab Alone or in Combination With Novel Agents in Subjects With NSCLC

Stage III Non-small Cell Lung Cancer Clinical Trial

— COAST  

Official title:

A Phase 2 Open-label, Multicenter, Randomized, Multidrug Platform Study of Durvalumab (MEDI4736) Alone or in Combination With Novel Agents in Subjects With Locally Advanced, Unresectable (Stage III) Non-small Cell Lung Cancer (COAST)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03822351
• Other study ID #: D9108C00001
• Secondary ID: 2018-002931-35
• Status: Completed
• Phase: Phase 2
• Start date: December 19, 2018
• Est. completion date: July 18, 2023

Study information

• Verified date: December 2023
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the clinical activity of durvalumab alone vs durvalumab in combination with novel agents. The overall study goal is early identification of novel durvalumab combinations that are more active than durvalumab alone in the treatment of patients with unresectable, Stage III NSCLC who have not progressed after cCRT.

Description:

Study D9108C00001 (COAST) is a Phase 2, open-label, multicenter, randomized multidrug platform study assessing the efficacy and safety of durvalumab alone vs durvalumab in combination with novel agents in subjects with locally advanced, unresectable, Stage III non-small cell lung cancer (NSCLC).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 188
• Est. completion date: July 18, 2023
• Est. primary completion date: July 18, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Main Inclusion Criteria:

1. Written informed consent and any locally required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluation

2. Age 18 years or older

3. Body weight = 35 kg

4. Subjects must have histologically or cytologically documented NSCLC who present with locally advanced, unresectable, Stage III disease

5. Subjects must have completed, without progressing, definitive cCRT within 42 days prior to being randomized into the study:

6. Provision of tumor tissue sample, when available, from original diagnosis obtained before initiation of chemoradiotherapy

7. Life expectancy = 12 weeks

8. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

9. Subjects must have at least one previously irradiated tumor lesion that can be measured by RECIST v1.1

Main Exclusion Criteria:

1. Mixed small cell and non-small cell lung cancer histology

2. Current or prior use of immunosuppressive medication within 14 days before the first dose of study drug.

3. Prior exposure to any anti-PD1, anti-PD-L1, or anti-CTLA4 antibody for treatment of NSCLC

4. Subjects with history of = Grade 2 pneumonitis from prior chemoradiation therapy

5. Subjects with a history of venous thrombosis within the past 3 months

6. Subjects with history of myocardial infarction, transient ischemic attack, or stroke in the past 6 months

7. Congestive heart failure

8. Active or prior documented autoimmune or inflammatory disorders

9. History of active primary immunodeficiency

10. Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)

11. History of allogenic organ transplantation

12. QTcF interval = 470 ms

13. History of another primary malignancy

14. Concurrent enrollment in another therapeutic clinical study or during the follow-up period of an interventional study. Enrollment in observational studies will be allowed

15. Females who are pregnant, lactating, or intend to become pregnant during their participation in the study

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Stage III Non-small Cell Lung Cancer
• Unresectable

Intervention

Drug:
• Durvalumab + Oleclumab
Durvalumab + Oleclumab
• Durvalumab
Durvalumab
• Durvalumab + Monalizumab
Durvalumab + Monalizumab

Locations

Country	Name	City	State
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Toronto	Ontario
France	Research Site	Bordeaux Cedex
France	Research Site	Brest
France	Research Site	Bron
France	Research Site	Creteil
France	Research Site	La Rochelle Cedex
France	Research Site	Lille
France	Research Site	Limoges Cedex
France	Research Site	Lyon Cedex 04
France	Research Site	Marseille Cedex 20
France	Research Site	Nice
France	Research Site	Pierre Benite
France	Research Site	Rennes Cedex 9
France	Research Site	STRASBOURG Cedex
France	Research Site	Toulouse
Hong Kong	Research Site	Hong Kong
Hong Kong	Research Site	Jordan
Hong Kong	Research Site	Kowloon
Italy	Research Site	Catania
Italy	Research Site	Cremona
Italy	Research Site	Milano
Italy	Research Site	Milano
Italy	Research Site	Palermo
Italy	Research Site	Ravenna
Italy	Research Site	Siena
Poland	Research Site	Gdynia
Poland	Research Site	Lodz
Poland	Research Site	Lodz
Portugal	Research Site	Lisboa
Portugal	Research Site	Lisboa
Portugal	Research Site	Porto
Portugal	Research Site	Porto
Spain	Research Site	A Coruña
Spain	Research Site	Badajoz
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Castelló de la Plana
Spain	Research Site	Madrid
Spain	Research Site	Málaga
Spain	Research Site	Valencia
Taiwan	Research Site	Chiayi
Taiwan	Research Site	Taichung
United States	Research Site	Anaheim	California
United States	Research Site	Baton Rouge	Louisiana
United States	Research Site	Covington	Louisiana
United States	Research Site	Duarte	California
United States	Research Site	Germantown	Tennessee
United States	Research Site	Gettysburg	Pennsylvania
United States	Research Site	Lancaster	Pennsylvania
United States	Research Site	Lexington	Kentucky
United States	Research Site	Lincoln	Nebraska
United States	Research Site	Louisville	Kentucky
United States	Research Site	Memphis	Tennessee
United States	Research Site	New Haven	Connecticut
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Orlando	Florida
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Portland	Oregon
United States	Research Site	Richmond	Virginia
United States	Research Site	Rosedale	Maryland
United States	Research Site	Sacramento	California
United States	Research Site	Salt Lake City	Utah
United States	Research Site	Sioux Falls	South Dakota
United States	Research Site	Tacoma	Washington
United States	Research Site	Tyler	Texas
United States	Research Site	Washington	District of Columbia
United States	Research Site	West Haven	Connecticut
United States	Research Site	Wichita	Kansas
United States	Research Site	Winter Haven	Florida

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Countries where clinical trial is conducted

United States,  Canada,  France,  Hong Kong,  Italy,  Poland,  Portugal,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response (OR) rate as a measure of antitumor activity of durvalumab alone vs durvalumab in combination with novel agents	Best overall response of confirmed CR or confirmed PR according to RECIST v1.1	ORR at 16weeks after randomization is the timing for radiologic assessment of the primary endpoint
Secondary	Incidence of Adverse Events as a measure of safety during the treatment period	The secondary endpoint of safety as assessed by the presence of adverse events and serious adverse events	From time of informed consent through treatment period (12 months) or up to 3 months post last dose of study treatment
Secondary	Duration of Response (DoR) as a measure of efficacy of durvalumab alone vs durvalumab in combination with novel agents	The duration from the first documentation of a subsequently confirmed OR to the first documentation of a disease progression according to RECIST v1.1 or death due to any cause, whichever occurs first. Only subjects who have achieved OR (confirmed CR or confirmed PR) will be evaluated for DoR	From time of first documented response until disease progression or up to a maximum of 5 years after randomization
Secondary	Disease Control (DC) as a measure of efficacy of durvalumab alone vs durvalumab in combination with novel agents	confirmed CR, confirmed PR, or SD based on RECIST v1.1	From time of randomization until disease progression or up to a maximum of 5 years
Secondary	Progression-Free Survival (PFS) and Progression-Free Survival 12 month landmark rate (PFS-12) as a measure of efficacy of durvalumab alone vs durvalumab in combination with novel agents	From randomization until the first documentation of disease progression according to RECIST v1.1 or death due to any cause, whichever occurs first	From time of randomization until disease progression or up to a maximum of 5 years
Secondary	Serum durvalumab concentration levels	Pharmacokinetics of durvalumab	From randomization up to 15 months after first treatment
Secondary	Serum concentration levels of durvalumab or novel agents	Pharmacokinetics of durvalumab alone and/or in combination with novel agents	From randomization up to 15 months after first treatment
Secondary	Development of detectable anti-drug antibody (ADA) to durvalumab	Immunogenicity of durvalumab	From randomization up to 15 months after first treatment
Secondary	Development of detectable anti-drug antibody (ADA) to durvalumab or novel biologic agents	Immunogenicity of durvalumab alone and/or in combination with novel biologic agents	From randomization up to 15 months after first treatment
Secondary	Number of patients with clinically significant laboratory values as a measure of safety	Assess the presence of clinically significant laboratory values taken at times indicated in the assessment schedule from baseline in terms of number of patients with abnormal values	From screening until disease progression or death, up to a maximum of 5 years after randomization
Secondary	Incidence of clinically significant vital sign values as a measure of safety	Assess the presence of clinically significant vital sign values from baseline	From screening until disease progression or death, up to a maximum of 5 years after randomization