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 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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
189
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.
Time frame: ORR at 16 weeks after randomization is the timing for radiologic assessment of the primary endpoint
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
Time frame: 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
Time frame: 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
Time frame: 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
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Research Site
Anaheim, California, United States
Research Site
Duarte, California, United States
Research Site
Sacramento, California, United States
Research Site
New Haven, Connecticut, United States
Research Site
West Haven, Connecticut, United States
Research Site
Washington D.C., District of Columbia, United States
Research Site
Orlando, Florida, United States
Research Site
Winter Haven, Florida, United States
Research Site
Wichita, Kansas, United States
Research Site
Lexington, Kentucky, United States
...and 63 more locations
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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