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

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.

Study Overview

• Status: Completed
• Conditions: Stage III Non-small Cell Lung Cancer; Unresectable
• Intervention / Treatment: Drug: Durvalumab; Drug: Durvalumab + Oleclumab; Drug: Durvalumab + Monalizumab

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).

• Study Type: Interventional
• Enrollment (Actual): 189
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Research Site
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Research Site
• France
  • Bordeaux Cedex, France, 33076
    • Research Site
  • Brest, France, 29609
    • Research Site
  • Bron, France, 69677
    • Research Site
  • Creteil, France, 94010
    • Research Site
  • La Rochelle Cedex, France, 17019
    • Research Site
  • Lille, France, 59037
    • Research Site
  • Limoges Cedex, France, 87042
    • Research Site
  • Lyon Cedex 04, France, 69004
    • Research Site
  • Marseille Cedex 20, France, 13015
    • Research Site
  • Nice, France, 06189
    • Research Site
  • Pierre Benite, France, 69495
    • Research Site
  • Rennes Cedex 9, France, 35033
    • Research Site
  • STRASBOURG Cedex, France, 67065
    • Research Site
  • Toulouse, France, 31059
    • Research Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Research Site
  • Jordan, Hong Kong
    • Research Site
  • Kowloon, Hong Kong
    • Research Site
• Italy
  • Catania, Italy, 95125
    • Research Site
  • Cremona, Italy, 26100
    • Research Site
  • Milano, Italy, 20132
    • Research Site
  • Milano, Italy, 20133
    • Research Site
  • Palermo, Italy, 90127
    • Research Site
  • Ravenna, Italy, 48121
    • Research Site
  • Siena, Italy, 53100
    • Research Site
• Poland
  • Gdynia, Poland, 81-519
    • Research Site
  • Lodz, Poland, 90-153
    • Research Site
  • Lodz, Poland, 90-242
    • Research Site
• Portugal
  • Lisboa, Portugal, 1500-650
    • Research Site
  • Lisboa, Portugal, 1400-038
    • Research Site
  • Porto, Portugal, 4099-001
    • Research Site
  • Porto, Portugal, 4200-072
    • Research Site
• Spain
  • A Coruña, Spain, 15006
    • Research Site
  • Badajoz, Spain, 06008
    • Research Site
  • Barcelona, Spain, 08035
    • Research Site
  • Barcelona, Spain, 08041
    • Research Site
  • Barcelona, Spain, 08916
    • Research Site
  • Castelló de la Plana, Spain, 12002
    • Research Site
  • Madrid, Spain, 28034
    • Research Site
  • Málaga, Spain, 29010
    • Research Site
  • Valencia, Spain, 46014
    • Research Site
• Taiwan
  • Chiayi, Taiwan, 61363
    • Research Site
  • Taichung, Taiwan, 402
    • Research Site
• United States
  • California
    • Anaheim, California, United States, 92801
      • Research Site
    • Duarte, California, United States, 91010
      • Research Site
    • Sacramento, California, United States, 95825
      • Research Site
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Research Site
    • West Haven, Connecticut, United States, 06516
      • Research Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Research Site
  • Florida
    • Orlando, Florida, United States, 32804
      • Research Site
    • Winter Haven, Florida, United States, 33881
      • Research Site
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Research Site
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Research Site
    • Louisville, Kentucky, United States, 40202
      • Research Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Research Site
    • Covington, Louisiana, United States, 70433
      • Research Site
  • Maryland
    • Rosedale, Maryland, United States, 21237
      • Research Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Research Site
  • New York
    • New York, New York, United States, 10065
      • Research Site
    • New York, New York, United States, 10029
      • Research Site
  • Oregon
    • Portland, Oregon, United States, 97227-1191
      • Research Site
  • Pennsylvania
    • Gettysburg, Pennsylvania, United States, 17325
      • Research Site
    • Lancaster, Pennsylvania, United States, 17601
      • Research Site
    • Philadelphia, Pennsylvania, United States, 19104
      • Research Site
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Research Site
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Research Site
    • Memphis, Tennessee, United States, 38120
      • Research Site
  • Texas
    • Tyler, Texas, United States, 75701
      • Research Site
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Research Site
  • Virginia
    • Richmond, Virginia, United States, 23230
      • Research Site
  • Washington
    • Tacoma, Washington, United States, 98405
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Control Arm (Durvalumab monotherapy); durvalumab IV	Drug: Durvalumab; Durvalumab; Other Names: Durvalumab (MEDI-4736)
Experimental: Arm A (durvalumab + oleclumab): durvalumab IV and oleclumab IV	Drug: Durvalumab + Oleclumab; Durvalumab + Oleclumab; Other Names: Durvalumab (MEDI-4736); Oleclumab (MEDI-9447)
Experimental: Arm B (durvalumab + monalizumab); durvalumab IV and monalizumab IV	Drug: Durvalumab + Monalizumab; Durvalumab + Monalizumab; Other Names: Durvalumab (MEDI-4736); Monalizumab (IPH2201)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	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	The secondary endpoint of safety as assessed by the presence of abnormal vital signs reported as adverse events	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	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	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	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.	Up to approximately 54 months (through the database cutoff date of 18-Jul-2023).
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	Up to approximately 54 months (through the database cutoff date of 18-Jul-2023).
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.	PFS rate at 12 months after randomization.
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.	From time of randomization until death due to any cause. Assessed through the database cutoff date of 18-Jul-2023).
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.	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
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.	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
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.	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
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.	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

Collaborators and Investigators

• Sponsor: MedImmune LLC

Publications and helpful links

General Publications

• 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.

Helpful Links

• CSP redacted
• SAP redacted
• CSR Synopsis redacted

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2018
• Primary Completion (Actual): July 18, 2023
• Study Completion (Actual): July 18, 2023

Study Registration Dates

• First Submitted: December 10, 2018
• First Submitted That Met QC Criteria: January 29, 2019
• First Posted (Actual): January 30, 2019

Study Record Updates

• Last Update Posted (Actual): October 8, 2024
• Last Update Submitted That Met QC Criteria: October 4, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Cancer; Unresectable; Lung; Non-small Cell Lung Cancer; Stage III; Locally Advanced NSCLC
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Durvalumab; Antibodies, Monoclonal
• Other Study ID Numbers: D9108C00001; 2018-002931-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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 Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No