NCT03822351

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
189

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Dec 2018

Typical duration for phase_2

Geographic Reach
9 countries

73 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 10, 2018

Completed
9 days until next milestone

Study Start

First participant enrolled

December 19, 2018

Completed
1 month until next milestone

First Posted

Study publicly available on registry

January 30, 2019

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 18, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 18, 2023

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

October 8, 2024

Completed
Last Updated

October 8, 2024

Status Verified

October 1, 2024

Enrollment Period

4.6 years

First QC Date

December 10, 2018

Results QC Date

July 1, 2024

Last Update Submit

October 4, 2024

Conditions

Keywords

Locally Advanced NSCLCNon-small Cell Lung CancerCancerLungUnresectableStage III

Outcome Measures

Primary Outcomes (1)

  • Objective Response (OR) Rate as a Measure of Antitumor Activity of Durvalumab Alone vs Durvalumab in Combination With Novel Agents

    ORR was defined as the percentage of participants with at least one visit response of Complete Response (CR) or Partial Response (PR) per RECIST 1.1 for target lesions: CR: Disappearance of all target lesions; PR: \>=30% decrease in the sum of the longest diameter of target lesions; OR = CR + PR.

    ORR at 16 weeks after randomization is the timing for radiologic assessment of the primary endpoint

Secondary Outcomes (12)

  • Presence of Adverse Events as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents

    From time of signature of informed consent up to 15 months post the first dose of study treatment

  • Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents

    From baseline up to 15 months post the first dose of study treatment

  • Presence of Abnormalities in Vital Signs as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents

    From baseline up to 15 months post the first dose of study treatment

  • Duration of Response (DoR) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents

    Up to approximately 54 months (through the database cutoff date of 18-Jul-2023).

  • Disease Control (DC) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents

    Up to approximately 54 months (through the database cutoff date of 18-Jul-2023).

  • +7 more secondary outcomes

Study Arms (3)

Control Arm (Durvalumab monotherapy)

EXPERIMENTAL

durvalumab IV

Drug: Durvalumab

Arm A (durvalumab + oleclumab):

EXPERIMENTAL

durvalumab IV and oleclumab IV

Drug: Durvalumab + Oleclumab

Arm B (durvalumab + monalizumab)

EXPERIMENTAL

durvalumab IV and monalizumab IV

Drug: Durvalumab + Monalizumab

Interventions

Durvalumab + Oleclumab

Also known as: Durvalumab (MEDI-4736), Oleclumab (MEDI-9447)
Arm A (durvalumab + oleclumab):

Durvalumab

Also known as: Durvalumab (MEDI-4736)
Control Arm (Durvalumab monotherapy)

Durvalumab + Monalizumab

Also known as: Durvalumab (MEDI-4736), Monalizumab (IPH2201)
Arm B (durvalumab + monalizumab)

Eligibility Criteria

Age18 Years - 99 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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 clinical study \[concurrent enrollment in an observational (non-interventional) clinical study or during the follow-up period of an interventional study is permitted\]
  • Females who are pregnant, lactating, or intend to become pregnant during their participation in the study

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (73)

Research Site

Anaheim, California, 92801, United States

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Duarte, California, 91010, United States

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Sacramento, California, 95825, United States

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New Haven, Connecticut, 06510, United States

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West Haven, Connecticut, 06516, United States

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Washington D.C., District of Columbia, 20007, United States

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Orlando, Florida, 32804, United States

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Winter Haven, Florida, 33881, United States

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Wichita, Kansas, 67214, United States

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Lexington, Kentucky, 40503, United States

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Louisville, Kentucky, 40202, United States

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Baton Rouge, Louisiana, 70809, United States

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Covington, Louisiana, 70433, United States

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Rosedale, Maryland, 21237, United States

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Lincoln, Nebraska, 68510, United States

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New York, New York, 10029, United States

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New York, New York, 10065, United States

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Portland, Oregon, 97227-1191, United States

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Gettysburg, Pennsylvania, 17325, United States

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Lancaster, Pennsylvania, 17601, United States

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Philadelphia, Pennsylvania, 19104, United States

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Sioux Falls, South Dakota, 57105, United States

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Germantown, Tennessee, 38138, United States

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Memphis, Tennessee, 38120, United States

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Tyler, Texas, 75701, United States

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Salt Lake City, Utah, 84112, United States

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Richmond, Virginia, 23230, United States

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Tacoma, Washington, 98405, United States

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Edmonton, Alberta, T6G 1Z2, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Montreal, Quebec, H4A 3J1, Canada

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Bordeaux, 33076, France

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Brest, 29609, France

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Bron, 69677, France

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Créteil, 94010, France

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La Rochelle, 17019, France

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Lille, 59037, France

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Limoges, 87042, France

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Lyon, 69004, France

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Marseille, 13015, France

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Nice, 06189, France

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Pierre-Bénite, 69495, France

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Rennes, 35033, France

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Strasbourg, 67065, France

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Toulouse, 31059, France

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Hong Kong, Hong Kong

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Jordan, Hong Kong

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Kowloon, Hong Kong

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Catania, 95125, Italy

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Cremona, 26100, Italy

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Milan, 20132, Italy

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Milan, 20133, Italy

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Palermo, 90127, Italy

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Ravenna, 48121, Italy

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Siena, 53100, Italy

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Gdynia, 81-519, Poland

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Lodz, 90-153, Poland

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Lodz, 90-242, Poland

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Lisbon, 1400-038, Portugal

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Lisbon, 1500-650, Portugal

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Porto, 4099-001, Portugal

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Porto, 4200-072, Portugal

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A Coruña, 15006, Spain

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Badajoz, 06008, Spain

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Barcelona, 08035, Spain

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Barcelona, 08041, Spain

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Barcelona, 08916, Spain

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Castellon, 12002, Spain

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Madrid, 28034, Spain

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Málaga, 29010, Spain

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Valencia, 46014, Spain

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Chiayi City, 61363, Taiwan

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Taichung, 402, Taiwan

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Related Publications (2)

  • Aggarwal C, Martinez-Marti A, Majem M, Barlesi F, Carcereny E, Chu Q, Monnet I, Sanchez-Hernandez A, Dakhil S, Camidge DR, Pillet M, Brown M, Paliompeis C, Dowson A, Cooper ZA, Kumar R, Herbst RS. Durvalumab Alone or Combined With Novel Agents for Unresectable Stage III Non-Small Cell Lung Cancer: Update From the COAST Randomized Clinical Trial. JAMA Netw Open. 2025 Jul 1;8(7):e2518440. doi: 10.1001/jamanetworkopen.2025.18440.

  • 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.

Related Links

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell LungNeoplasms

Interventions

durvalumabmonalizumab

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteLung DiseasesRespiratory Tract Diseases

Results Point of Contact

Title
Global Clinical Lead
Organization
AstraZeneca Clinical Study Information Center

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 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.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 10, 2018

First Posted

January 30, 2019

Study Start

December 19, 2018

Primary Completion

July 18, 2023

Study Completion

July 18, 2023

Last Updated

October 8, 2024

Results First Posted

October 8, 2024

Record last verified: 2024-10

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL, SAP
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.
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.
More information

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