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.
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
Drug | Synonyms | Arms |
---|
Durvalumab + Oleclumab | Durvalumab (MEDI-4736), Oleclumab (MEDI-9447) | Arm A (durvalumab + oleclumab): |
Durvalumab | Durvalumab (MEDI-4736) | Control Arm (Durvalumab monotherapy) |
Durvalumab + Monalizumab | Durvalumab (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
Name | Type | Description | Interventions |
---|
Control Arm (Durvalumab monotherapy) | Experimental | durvalumab IV | |
Arm A (durvalumab + oleclumab): | Experimental | durvalumab IV and oleclumab IV | |
Arm B (durvalumab + monalizumab) | Experimental | durvalumab IV and monalizumab IV | |
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: | Active, not recruiting |
Lead Sponsor: | MedImmune LLC |
Trial Keywords
- Locally Advanced NSCLC
- Non-small Cell Lung Cancer
- Cancer
- Lung
- Unresectable
- Stage III
Last Updated
August 4, 2021