Clinical Trials /

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

NCT03822351

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: D9108C00001
  • NCT ID: NCT03822351

Conditions

  • Stage III Non-small Cell Lung Cancer
  • Unresectable

Interventions

DrugSynonymsArms
Durvalumab + OleclumabDurvalumab (MEDI-4736), Oleclumab (MEDI-9447)Arm A (durvalumab + oleclumab):
DurvalumabDurvalumab (MEDI-4736)Control Arm (Durvalumab monotherapy)
Durvalumab + MonalizumabDurvalumab (MEDI-4736), Monalizumab (IPH2201)Arm B (durvalumab + monalizumab)

Purpose

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).
    

Trial Arms

NameTypeDescriptionInterventions
Control Arm (Durvalumab monotherapy)Experimentaldurvalumab IV
  • Durvalumab
Arm A (durvalumab + oleclumab):Experimentaldurvalumab IV and oleclumab IV
  • Durvalumab + Oleclumab
Arm B (durvalumab + monalizumab)Experimentaldurvalumab IV and monalizumab IV
  • Durvalumab + Monalizumab

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 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
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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 16weeks after randomization is the timing for radiologic assessment of the primary endpoint
Safety Issue:
Description:Best overall response of confirmed CR or confirmed PR according to RECIST v1.1

Secondary Outcome Measures

Measure:Incidence of Adverse Events as a measure of safety during the treatment period
Time Frame:From time of informed consent through treatment period (12 months) or up to 3 months post last dose of study treatment
Safety Issue:
Description:The secondary endpoint of safety as assessed by the presence of adverse events and serious adverse events
Measure:Duration of Response (DoR) as a measure of efficacy of durvalumab alone vs durvalumab in combination with novel agents
Time Frame:From time of first documented response until disease progression or up to a maximum of 5 years after randomization
Safety Issue:
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
Measure:Disease Control (DC) as a measure of efficacy of durvalumab alone vs durvalumab in combination with novel agents
Time Frame:From time of randomization until disease progression or up to a maximum of 5 years
Safety Issue:
Description:confirmed CR, confirmed PR, or SD based on RECIST v1.1
Measure: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
Time Frame:From time of randomization until disease progression or up to a maximum of 5 years
Safety Issue:
Description:From randomization until the first documentation of disease progression according to RECIST v1.1 or death due to any cause, whichever occurs first
Measure:Serum durvalumab concentration levels
Time Frame:From randomization up to 15 months after first treatment
Safety Issue:
Description:Pharmacokinetics of durvalumab
Measure:Serum concentration levels of durvalumab or novel agents
Time Frame:From randomization up to 15 months after first treatment
Safety Issue:
Description:Pharmacokinetics of durvalumab alone and/or in combination with novel agents
Measure:Development of detectable anti-drug antibody (ADA) to durvalumab
Time Frame:From randomization up to 15 months after first treatment
Safety Issue:
Description:Immunogenicity of durvalumab
Measure:Development of detectable anti-drug antibody (ADA) to durvalumab or novel biologic agents
Time Frame:From randomization up to 15 months after first treatment
Safety Issue:
Description:Immunogenicity of durvalumab alone and/or in combination with novel biologic agents
Measure:Number of patients with clinically significant laboratory values as a measure of safety
Time Frame:From screening until disease progression or death, up to a maximum of 5 years after randomization
Safety Issue:
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
Measure:Incidence of clinically significant vital sign values as a measure of safety
Time Frame:From screening until disease progression or death, up to a maximum of 5 years after randomization
Safety Issue:
Description:Assess the presence of clinically significant vital sign values from baseline

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:MedImmune LLC

Trial Keywords

  • Locally Advanced NSCLC
  • Non-small Cell Lung Cancer
  • Cancer
  • Lung
  • Unresectable
  • Stage III

Last Updated

January 17, 2020