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Durvalumab Alone or in Combination With Novel Agents in Subjects With NSCLC (COAST)

Primary Purpose

Stage III Non-small Cell Lung Cancer, Unresectable

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Durvalumab + Oleclumab
Durvalumab
Durvalumab + Monalizumab
Sponsored by
MedImmune LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stage III Non-small Cell Lung Cancer focused on measuring Locally Advanced NSCLC, Non-small Cell Lung Cancer, Cancer, Lung, Unresectable, Stage III

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Control Arm (Durvalumab monotherapy)

Arm A (durvalumab + oleclumab):

Arm B (durvalumab + monalizumab)

Arm Description

durvalumab IV

durvalumab IV and oleclumab IV

durvalumab IV and monalizumab IV

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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
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
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
Serum durvalumab concentration levels
Pharmacokinetics of durvalumab
Serum concentration levels of durvalumab or novel agents
Pharmacokinetics of durvalumab alone and/or in combination with novel agents
Development of detectable anti-drug antibody (ADA) to durvalumab
Immunogenicity of durvalumab
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
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
Incidence of clinically significant vital sign values as a measure of safety
Assess the presence of clinically significant vital sign values from baseline

Full Information

First Posted
December 10, 2018
Last Updated
February 17, 2023
Sponsor
MedImmune LLC
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1. Study Identification

Unique Protocol Identification Number
NCT03822351
Brief Title
Durvalumab Alone or in Combination With Novel Agents in Subjects With NSCLC
Acronym
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)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 19, 2018 (Actual)
Primary Completion Date
June 21, 2023 (Anticipated)
Study Completion Date
June 21, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MedImmune LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.
Detailed 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage III Non-small Cell Lung Cancer, Unresectable
Keywords
Locally Advanced NSCLC, Non-small Cell Lung Cancer, Cancer, Lung, Unresectable, Stage III

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Factorial Assignment
Model Description
At study onset subjects will be randomized equally to all study treatment arms open for enrollment and will remain on study treatment for up to 12 months. Study treatment will be discontinued upon disease progression, unacceptable toxicity, or other reason. The treatment arms are Control Arm, Arm A and Arm B.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
188 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Control Arm (Durvalumab monotherapy)
Arm Type
Experimental
Arm Description
durvalumab IV
Arm Title
Arm A (durvalumab + oleclumab):
Arm Type
Experimental
Arm Description
durvalumab IV and oleclumab IV
Arm Title
Arm B (durvalumab + monalizumab)
Arm Type
Experimental
Arm Description
durvalumab IV and monalizumab IV
Intervention Type
Drug
Intervention Name(s)
Durvalumab + Oleclumab
Other Intervention Name(s)
Durvalumab (MEDI-4736), Oleclumab (MEDI-9447)
Intervention Description
Durvalumab + Oleclumab
Intervention Type
Drug
Intervention Name(s)
Durvalumab
Other Intervention Name(s)
Durvalumab (MEDI-4736)
Intervention Description
Durvalumab
Intervention Type
Drug
Intervention Name(s)
Durvalumab + Monalizumab
Other Intervention Name(s)
Durvalumab (MEDI-4736), Monalizumab (IPH2201)
Intervention Description
Durvalumab + Monalizumab
Primary Outcome Measure Information:
Title
Objective Response (OR) rate as a measure of antitumor activity of durvalumab alone vs durvalumab in combination with novel agents
Description
Best overall response of confirmed CR or confirmed PR according to RECIST v1.1
Time Frame
ORR at 16weeks after randomization is the timing for radiologic assessment of the primary endpoint
Secondary Outcome Measure Information:
Title
Incidence of Adverse Events as a measure of safety during the treatment period
Description
The secondary endpoint of safety as assessed by the presence of adverse events and serious adverse events
Time Frame
From time of informed consent through treatment period (12 months) or up to 3 months post last dose of study treatment
Title
Duration of Response (DoR) as a measure of efficacy of durvalumab alone vs durvalumab in combination with novel agents
Description
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
Time Frame
From time of first documented response until disease progression or up to a maximum of 5 years after randomization
Title
Disease Control (DC) as a measure of efficacy of durvalumab alone vs durvalumab in combination with novel agents
Description
confirmed CR, confirmed PR, or SD based on RECIST v1.1
Time Frame
From time of randomization until disease progression or up to a maximum of 5 years
Title
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
Description
From randomization until the first documentation of disease progression according to RECIST v1.1 or death due to any cause, whichever occurs first
Time Frame
From time of randomization until disease progression or up to a maximum of 5 years
Title
Serum durvalumab concentration levels
Description
Pharmacokinetics of durvalumab
Time Frame
From randomization up to 15 months after first treatment
Title
Serum concentration levels of durvalumab or novel agents
Description
Pharmacokinetics of durvalumab alone and/or in combination with novel agents
Time Frame
From randomization up to 15 months after first treatment
Title
Development of detectable anti-drug antibody (ADA) to durvalumab
Description
Immunogenicity of durvalumab
Time Frame
From randomization up to 15 months after first treatment
Title
Development of detectable anti-drug antibody (ADA) to durvalumab or novel biologic agents
Description
Immunogenicity of durvalumab alone and/or in combination with novel biologic agents
Time Frame
From randomization up to 15 months after first treatment
Title
Number of patients with clinically significant laboratory values as a measure of safety
Description
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
Time Frame
From screening until disease progression or death, up to a maximum of 5 years after randomization
Title
Incidence of clinically significant vital sign values as a measure of safety
Description
Assess the presence of clinically significant vital sign values from baseline
Time Frame
From screening until disease progression or death, up to a maximum of 5 years after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Main Inclusion Criteria: Written informed consent and any locally required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluation Age 18 years or older Body weight ≥ 35 kg Subjects must have histologically or cytologically documented NSCLC who present with locally advanced, unresectable, Stage III disease Subjects must have completed, without progressing, definitive cCRT within 42 days prior to being randomized into the study: Provision of tumor tissue sample, when available, from original diagnosis obtained before initiation of chemoradiotherapy Life expectancy ≥ 12 weeks Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 Subjects must have at least one previously irradiated tumor lesion that can be measured by RECIST v1.1 Main Exclusion Criteria: Mixed small cell and non-small cell lung cancer histology Current or prior use of immunosuppressive medication within 14 days before the first dose of study drug. Prior exposure to any anti-PD1, anti-PD-L1, or anti-CTLA4 antibody for treatment of NSCLC Subjects with history of ≥ Grade 2 pneumonitis from prior chemoradiation therapy Subjects with a history of venous thrombosis within the past 3 months Subjects with history of myocardial infarction, transient ischemic attack, or stroke in the past 6 months Congestive heart failure Active or prior documented autoimmune or inflammatory disorders History of active primary immunodeficiency Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) History of allogenic organ transplantation QTcF interval ≥ 470 ms History of another primary malignancy Concurrent enrollment in another therapeutic clinical study or during the follow-up period of an interventional study. Enrollment in observational studies will be allowed Females who are pregnant, lactating, or intend to become pregnant during their participation in the study
Facility Information:
Facility Name
Research Site
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
Facility Name
Research Site
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Research Site
City
Sacramento
State/Province
California
ZIP/Postal Code
95825
Country
United States
Facility Name
Research Site
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Research Site
City
West Haven
State/Province
Connecticut
ZIP/Postal Code
06516
Country
United States
Facility Name
Research Site
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Research Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Facility Name
Research Site
City
Winter Haven
State/Province
Florida
ZIP/Postal Code
33881
Country
United States
Facility Name
Research Site
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
Research Site
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40503
Country
United States
Facility Name
Research Site
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Research Site
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70809
Country
United States
Facility Name
Research Site
City
Covington
State/Province
Louisiana
ZIP/Postal Code
70433
Country
United States
Facility Name
Research Site
City
Rosedale
State/Province
Maryland
ZIP/Postal Code
21237
Country
United States
Facility Name
Research Site
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68510
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Research Site
City
Portland
State/Province
Oregon
ZIP/Postal Code
97227-1191
Country
United States
Facility Name
Research Site
City
Gettysburg
State/Province
Pennsylvania
ZIP/Postal Code
17325
Country
United States
Facility Name
Research Site
City
Lancaster
State/Province
Pennsylvania
ZIP/Postal Code
17601
Country
United States
Facility Name
Research Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Research Site
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57105
Country
United States
Facility Name
Research Site
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
Research Site
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38120
Country
United States
Facility Name
Research Site
City
Tyler
State/Province
Texas
ZIP/Postal Code
75701
Country
United States
Facility Name
Research Site
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Research Site
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23230
Country
United States
Facility Name
Research Site
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Facility Name
Research Site
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
Research Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
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Research Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada
Facility Name
Research Site
City
Bordeaux Cedex
ZIP/Postal Code
33076
Country
France
Facility Name
Research Site
City
Brest
ZIP/Postal Code
29609
Country
France
Facility Name
Research Site
City
Bron
ZIP/Postal Code
69677
Country
France
Facility Name
Research Site
City
Creteil
ZIP/Postal Code
94010
Country
France
Facility Name
Research Site
City
La Rochelle Cedex
ZIP/Postal Code
17019
Country
France
Facility Name
Research Site
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Research Site
City
Limoges Cedex
ZIP/Postal Code
87042
Country
France
Facility Name
Research Site
City
Lyon Cedex 04
ZIP/Postal Code
69004
Country
France
Facility Name
Research Site
City
Marseille Cedex 20
ZIP/Postal Code
13015
Country
France
Facility Name
Research Site
City
Nice
ZIP/Postal Code
06189
Country
France
Facility Name
Research Site
City
Pierre Benite
ZIP/Postal Code
69495
Country
France
Facility Name
Research Site
City
Rennes Cedex 9
ZIP/Postal Code
35033
Country
France
Facility Name
Research Site
City
Strasbourg Cedex
ZIP/Postal Code
67085
Country
France
Facility Name
Research Site
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Research Site
City
Hong Kong
Country
Hong Kong
Facility Name
Research Site
City
Jordan
Country
Hong Kong
Facility Name
Research Site
City
Kowloon
Country
Hong Kong
Facility Name
Research Site
City
Catania
ZIP/Postal Code
95125
Country
Italy
Facility Name
Research Site
City
Cremona
ZIP/Postal Code
26100
Country
Italy
Facility Name
Research Site
City
Milano
ZIP/Postal Code
20132
Country
Italy
Facility Name
Research Site
City
Milano
ZIP/Postal Code
20133
Country
Italy
Facility Name
Research Site
City
Palermo
ZIP/Postal Code
90127
Country
Italy
Facility Name
Research Site
City
Ravenna
ZIP/Postal Code
48121
Country
Italy
Facility Name
Research Site
City
Siena
ZIP/Postal Code
53100
Country
Italy
Facility Name
Research Site
City
Gdynia
ZIP/Postal Code
81-519
Country
Poland
Facility Name
Research Site
City
Lodz
ZIP/Postal Code
90-153
Country
Poland
Facility Name
Research Site
City
Lodz
ZIP/Postal Code
90-242
Country
Poland
Facility Name
Research Site
City
Lisboa
ZIP/Postal Code
1400-038
Country
Portugal
Facility Name
Research Site
City
Lisboa
ZIP/Postal Code
1500-650
Country
Portugal
Facility Name
Research Site
City
Porto
ZIP/Postal Code
4099-001
Country
Portugal
Facility Name
Research Site
City
Porto
ZIP/Postal Code
4200-072
Country
Portugal
Facility Name
Research Site
City
A Coruña
ZIP/Postal Code
15006
Country
Spain
Facility Name
Research Site
City
Badajoz
ZIP/Postal Code
06008
Country
Spain
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Research Site
City
Castelló de la Plana
ZIP/Postal Code
12002
Country
Spain
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Research Site
City
Málaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Research Site
City
Valencia
ZIP/Postal Code
46014
Country
Spain
Facility Name
Research Site
City
Chiayi
ZIP/Postal Code
61363
Country
Taiwan
Facility Name
Research Site
City
Taichung
ZIP/Postal Code
402
Country
Taiwan

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing Access Criteria
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home
Citations:
PubMed Identifier
35452273
Citation
Herbst RS, Majem M, Barlesi F, Carcereny E, Chu Q, Monnet I, Sanchez-Hernandez A, Dakhil S, Camidge DR, Winzer L, Soo-Hoo Y, Cooper ZA, Kumar R, Bothos J, Aggarwal C, Martinez-Marti A. COAST: An Open-Label, Phase II, Multidrug Platform Study of Durvalumab Alone or in Combination With Oleclumab or Monalizumab in Patients With Unresectable, Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2022 Oct 10;40(29):3383-3393. doi: 10.1200/JCO.22.00227. Epub 2022 Apr 22.
Results Reference
derived

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

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