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Stage III Non-small Cell Lung CancerPhase 2COASTNCT03822351

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

A Phase 2 study testing Durvalumab + Oleclumab, Durvalumab and Durvalumab + Monalizumab in people with Stage III Non-small Cell Lung Cancer and Unresectable, run by MedImmune LLC at 73 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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… Read more about this study

Who is it for?
Ages 18 to 99 years
What is being tested?
Durvalumab + Oleclumab, Durvalumab and Durvalumab + Monalizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
189 participants
Where
73 sitesin 9 countries
Study dates
19 Dec 2018to 18 Jul 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

73 sites in 9 countries.

73 sites in 9 countries

United States28 sites

  • Research Site

    Anaheim, California, 92801

  • Research Site

    Baton Rouge, Louisiana, 70809

  • Research Site

    Covington, Louisiana, 70433

  • Research Site

    Duarte, California, 91010

  • Research Site

    Germantown, Tennessee, 38138

  • Research Site

    Gettysburg, Pennsylvania, 17325

  • Research Site

    Lancaster, Pennsylvania, 17601

  • Research Site

    Lexington, Kentucky, 40503

  • Research Site

    Lincoln, Nebraska, 68510

  • Research Site

    Louisville, Kentucky, 40202

  • Research Site

    Memphis, Tennessee, 38120

  • Research Site

    New Haven, Connecticut, 06510

  • Research Site

    New York, New York, 10029

  • Research Site

    New York, New York, 10065

  • Research Site

    Orlando, Florida, 32804

  • Research Site

    Philadelphia, Pennsylvania, 19104

  • Research Site

    Portland, Oregon, 97227-1191

  • Research Site

    Richmond, Virginia, 23230

  • Research Site

    Rosedale, Maryland, 21237

  • Research Site

    Sacramento, California, 95825

  • Research Site

    Salt Lake City, Utah, 84112

  • Research Site

    Sioux Falls, South Dakota, 57105

  • Research Site

    Tacoma, Washington, 98405

  • Research Site

    Tyler, Texas, 75701

  • Research Site

    Washington D.C., District of Columbia, 20007

  • Research Site

    West Haven, Connecticut, 06516

  • Research Site

    Wichita, Kansas, 67214

  • Research Site

    Winter Haven, Florida, 33881

Other trials in United States

France14 sites

  • Research Site

    Bordeaux, 33076

  • Research Site

    Brest, 29609

  • Research Site

    Bron, 69677

  • Research Site

    Créteil, 94010

  • Research Site

    La Rochelle, 17019

  • Research Site

    Lille, 59037

  • Research Site

    Limoges, 87042

  • Research Site

    Lyon, 69004

  • Research Site

    Marseille, 13015

  • Research Site

    Nice, 06189

  • Research Site

    Pierre-Bénite, 69495

  • Research Site

    Rennes, 35033

  • Research Site

    Strasbourg, 67065

  • Research Site

    Toulouse, 31059

Other trials in France

Spain9 sites

  • Research Site

    A Coruña, 15006

  • Research Site

    Badajoz, 06008

  • Research Site

    Barcelona, 08035

  • Research Site

    Barcelona, 08041

  • Research Site

    Barcelona, 08916

  • Research Site

    Castellon, 12002

  • Research Site

    Madrid, 28034

  • Research Site

    Málaga, 29010

  • Research Site

    Valencia, 46014

Other trials in Spain

Italy7 sites

  • Research Site

    Catania, 95125

  • Research Site

    Cremona, 26100

  • Research Site

    Milan, 20132

  • Research Site

    Milan, 20133

  • Research Site

    Palermo, 90127

  • Research Site

    Ravenna, 48121

  • Research Site

    Siena, 53100

Other trials in Italy

Portugal4 sites

  • Research Site

    Lisbon, 1400-038

  • Research Site

    Lisbon, 1500-650

  • Research Site

    Porto, 4099-001

  • Research Site

    Porto, 4200-072

Other trials in Portugal

Canada3 sites

  • Research Site

    Edmonton, Alberta, T6G 1Z2

  • Research Site

    Montreal, Quebec, H4A 3J1

  • Research Site

    Toronto, Ontario, M5G 2M9

Other trials in Canada

Hong Kong3 sites

  • Research Site

    Hong Kong

  • Research Site

    Jordan

  • Research Site

    Kowloon

Other trials in Hong Kong

Poland3 sites

  • Research Site

    Gdynia, 81-519

  • Research Site

    Lodz, 90-153

  • Research Site

    Lodz, 90-242

Other trials in Poland

Taiwan2 sites

  • Research Site

    Chiayi City, 61363

  • Research Site

    Taichung, 402

Other trials in Taiwan

About this study

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)

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.

Read the 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).

Being tested
Durvalumab + Oleclumab, Durvalumab, Durvalumab + Monalizumab
Keywords
Locally Advanced NSCLC, Non-small Cell Lung Cancer, Cancer, Lung, Unresectable, Stage III
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Durvalumab + OleclumabDrug

    Also called Durvalumab (MEDI-4736), Oleclumab (MEDI-9447)

    Durvalumab + Oleclumab

  • DurvalumabDrug

    Also called Durvalumab (MEDI-4736)

    Durvalumab

  • Durvalumab + MonalizumabDrug

    Also called Durvalumab (MEDI-4736), Monalizumab (IPH2201)

    Durvalumab + Monalizumab

Study groups in NCT03822351
Study groupRoleWhat they receive
Control Arm (Durvalumab monotherapy)Experimentaldurvalumab IV
Receives: Drug: Durvalumab
Arm A (durvalumab + oleclumab):Experimentaldurvalumab IV and oleclumab IV
Receives: Drug: Durvalumab + Oleclumab
Arm B (durvalumab + monalizumab)Experimentaldurvalumab IV and monalizumab IV
Receives: Drug: Durvalumab + Monalizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (12)

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

    The secondary endpoint of safety as assessed by the presence of adverse events and serious adverse events

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

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

    The secondary endpoint of safety as assessed by the presence of Grade 3 or 4 clinical laboratory toxicities (based on NCI-CTCAE v5.0) in chemistry and hematology values

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

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

    The secondary endpoint of safety as assessed by the presence of abnormal vital signs reported as adverse events

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

  4. 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 participants who have achieved OR (confirmed CR or confirmed PR) will be evaluated for DoR

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

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

    Disease control rate (DCR) was defined as the percentage of participants with a BOR of confirmed CR, confirmed PR, or SD (maintained for ≥ 16 weeks) based on RECIST v1.1.

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

  6. Progression-Free Survival (PFS) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents

    PFS was defined as the time from randomization until the first documentation of disease progression according to RECIST v1.1 or death due to any cause, whichever occurs first

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

  7. Progression-Free Survival 12 Month Landmark Rate (PFS-12) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents

    PFS-12 was defined as the percentage of participants who were alive and progression free at 12 months after randomization.

    Measured: PFS rate at 12 months after randomization.

  8. Overall Survival (OS) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents

    OS was defined as the time from the date of randomization until death due to any cause.

    Measured: From time of randomization until death due to any cause. Assessed through the database cutoff date of 18-Jul-2023).

  9. Pharmacokinetics of Durvalumab Alone and in Combination With Novel Agents

    Geometric mean serum concentrations of durvalumab (μg/mL) were reported for each time point where data warrant, as appropriate.

    Measured: From randomization up to 15 months after first treatment: Cycle 1 Day 1 pre-dose and at end of infusion, Cycle 2 Day 1 pre-dose (1 month), Cycle 7 Day 1 pre-dose (6 months), Cycle 11 Day 1 pre-dose (10 months) and 15 months post Cycle 1 Day 1

  10. Pharmacokinetics of Novel Agents in Combination With Durvalumab

    Geometric mean serum concentrations of oleclumab (μg/mL) and monalizumab (μg/mL) were reported for each time point where data warrant, as appropriate.

    Measured: From randomization up to 15 months after first treatment: Cycle 1 Day 1 pre-dose and at end of infusion, Cycle 2 Day 1 pre-dose (1 month), Cycle 7 Day 1 pre-dose (6 months), Cycle 11 Day 1 pre-dose (10 months) and 15 months post Cycle 1 Day 1

  11. Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents

    ADA prevalence was defined as the percentage of participants with positive ADA result at any time, baseline or post-baseline. ADA positive post-baseline only was also referred to as treatment-induced ADA positive. Treatment-boosted ADA was defined as baseline positive ADA titer that was boosted to a 4-fold or higher following drug administration. Persistently positive was defined as positive at ≥2 post-baseline assessments (with ≥16 weeks between first and last positive) or positive at last post-baseline assessment. Transiently positive was defined as having at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive.

    ADA incidence (treatment-emergent ADA positive) was defined as the sum of treatment-induced ADA and treatment-boosted ADA.

    Measured: From randomization up to 15 months after first treatment: Cycle 1 Day 1 pre-dose, Cycle 2 Day 1 pre-dose (1 month), Cycle 7 Day 1 pre-dose (6 months), Cycle 11 Day 1 pre-dose (10 months) and 15 months post Cycle 1 Day 1

  12. Presence of Detectable Anti-Drug Antibody (ADA) Response to Novel Agents in Combination With Durvalumab

    ADA prevalence was defined as the percentage of participants with positive ADA result at any time, baseline or post-baseline. ADA positive post-baseline only was also referred to as treatment-induced ADA positive. Treatment-boosted ADA was defined as baseline positive ADA titer that was boosted to a 4-fold or higher following drug administration. Persistently positive was defined as positive at ≥2 post-baseline assessments (with ≥16 weeks between first and last positive) or positive at last post-baseline assessment. Transiently positive was defined as having at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive.

    ADA incidence (treatment-emergent ADA positive) was defined as the sum of treatment-induced ADA and treatment-boosted ADA.

    Measured: From randomization up to 15 months after first treatment: Cycle 1 Day 1 pre-dose, Cycle 2 Day 1 pre-dose (1 month), Cycle 7 Day 1 pre-dose (6 months), Cycle 11 Day 1 pre-dose (10 months) and 15 months post Cycle 1 Day 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jan 2019
  2. Study start19 Dec 2018
  3. Primary completion18 Jul 2023
  4. Study completion18 Jul 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
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)
Enrolment
189 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03822351
Sponsor's protocol ID
D9108C00001
Other IDs
2018-002931-35, 2018
Acronym
COAST
Status last verified
Oct 2024
First submitted
10 Dec 2018
Last updated
8 Oct 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 40663352

  • 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.

    PubMed 35452273

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Durvalumab + Oleclumab, Durvalumab and Durvalumab + Monalizumab in people with Stage III Non-small Cell Lung Cancer and Unresectable, run by MedImmune LLC at 73 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 73 sites in United States, France, Spain, Italy, Portugal and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response (OR) Rate as a Measure of Antitumor Activity of Durvalumab Alone vs Durvalumab in Combination With Novel Agents (time frame: ORR at 16 weeks after randomization is the timing for radiologic assessment of the primary endpoint). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03822351, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2024.

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