Clinical trial NCT03822351: Durvalumab Alone or in Combination With Novel Agents in Subjects With NSCLC
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stage III Non-small Cell Lung Cancer
Unresectable
Keywords: Locally Advanced NSCLC
Non-small Cell Lung Cancer
Cancer
Lung
Unresectable
Stage III
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2019-01-30
Enrollment: 189
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: Objective Response (OR) Rate as a Measure of Antitumor Activity of Durvalumab Alone vs Durvalumab in Combination With Novel Agents
timeFrame: ORR at 16 weeks after randomization is the timing for radiologic assessment of the primary endpoint
Secondary outcomes:
measure: Presence of Adverse Events as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents
timeFrame: From time of signature of informed consent up to 15 months post the first dose of study treatment
measure: Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents
timeFrame: From baseline up to 15 months post the first dose of study treatment
measure: Presence of Abnormalities in Vital Signs as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents
timeFrame: From baseline up to 15 months post the first dose of study treatment
measure: Duration of Response (DoR) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents
timeFrame: Up to approximately 54 months (through the database cutoff date of 18-Jul-2023).
measure: Disease Control (DC) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents
timeFrame: Up to approximately 54 months (through the database cutoff date of 18-Jul-2023).
measure: Progression-Free Survival (PFS) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents
timeFrame: Up to approximately 54 months (through the database cutoff date of 18-Jul-2023).
measure: Progression-Free Survival 12 Month Landmark Rate (PFS-12) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents
timeFrame: PFS rate at 12 months after randomization.
measure: Overall Survival (OS) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents
timeFrame: From time of randomization until death due to any cause. Assessed through the database cutoff date of 18-Jul-2023).
measure: Pharmacokinetics of Durvalumab Alone and in Combination With Novel Agents
timeFrame: 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
measure: Pharmacokinetics of Novel Agents in Combination With Durvalumab
timeFrame: 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
measure: Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents
timeFrame: 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
measure: Presence of Detectable Anti-Drug Antibody (ADA) Response to Novel Agents in Combination With Durvalumab
timeFrame: 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
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Research Site
state: California
city: Duarte
country: United States
facility: Research Site
state: California
city: Sacramento
country: United States
facility: Research Site
state: California
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: West Haven
country: United States
facility: Research Site
state: Connecticut
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Winter Haven
country: United States
facility: Research Site
state: Florida
city: Wichita
country: United States
facility: Research Site
state: Kansas
city: Lexington
country: United States
facility: Research Site
state: Kentucky
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Baton Rouge
country: United States
facility: Research Site
state: Louisiana
city: Covington
country: United States
facility: Research Site
state: Louisiana
city: Rosedale
country: United States
facility: Research Site
state: Maryland
city: Lincoln
country: United States
facility: Research Site
state: Nebraska
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Gettysburg
country: United States
facility: Research Site
state: Pennsylvania
city: Lancaster
country: United States
facility: Research Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Research Site
state: South Dakota
city: Germantown
country: United States
facility: Research Site
state: Tennessee
city: Memphis
country: United States
facility: Research Site
state: Tennessee
city: Tyler
country: United States
facility: Research Site
state: Texas
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Richmond
country: United States
facility: Research Site
state: Virginia
city: Tacoma
country: United States
facility: Research Site
state: Washington
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Bordeaux Cedex
country: France
facility: Research Site
city: Brest
country: France
facility: Research Site
city: Bron
country: France
facility: Research Site
city: Creteil
country: France
facility: Research Site
city: La Rochelle Cedex
country: France
facility: Research Site
city: Lille
country: France
facility: Research Site
city: Limoges Cedex
country: France
facility: Research Site
city: Lyon Cedex 04
country: France
facility: Research Site
city: Marseille Cedex 20
country: France
facility: Research Site
city: Nice
country: France
facility: Research Site
city: Pierre Benite
country: France
facility: Research Site
city: Rennes Cedex 9
country: France
facility: Research Site
city: STRASBOURG Cedex
country: France
facility: Research Site
city: Toulouse
country: France
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Jordan
country: Hong Kong
facility: Research Site
city: Kowloon
country: Hong Kong
facility: Research Site
city: Catania
country: Italy
facility: Research Site
city: Cremona
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Palermo
country: Italy
facility: Research Site
city: Ravenna
country: Italy
facility: Research Site
city: Siena
country: Italy
facility: Research Site
city: Gdynia
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: A Coruña
country: Spain
facility: Research Site
city: Badajoz
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Castelló de la Plana
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Chiayi
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
Study officials:
References:
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.