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

Phase 2

Completed

• Conditions: Stage III Non-small Cell Lung Cancer; Unresectable
• Interventions: Drug: Durvalumab + Oleclumab; Drug: Durvalumab + Monalizumab; Drug: Durvalumab

• Registration Number: NCT03822351
• Lead Sponsor: MedImmune LLC

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).

Study Timeline

• Study First Submitted: 2018-12-10
• Study Start: 2018-12-19
• Study First Submitted QC: 2019-01-29
• Study First Posted: 2019-01-30
• Primary Completion: 2023-07-18
• Study Completion: 2023-07-18
• Results First Submitted: 2024-07-01
• Status Verified: 2024-10
• Results First Submitted QC: 2024-10-04
• Last Update Submitted: 2024-10-04
• Results First Posted: 2024-10-07
• Last Update Posted: 2024-10-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 189

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A (durvalumab + oleclumab):	Durvalumab + Oleclumab	durvalumab IV and oleclumab IV
Arm B (durvalumab + monalizumab)	Durvalumab + Monalizumab	durvalumab IV and monalizumab IV
Control Arm (Durvalumab monotherapy)	Durvalumab	durvalumab IV

Primary Outcome Measures

Name	Time	Method
Objective Response (OR) Rate as a Measure of Antitumor Activity of Durvalumab Alone vs Durvalumab in Combination With Novel Agents	ORR at 16 weeks after randomization is the timing for radiologic assessment of the primary endpoint	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.

Secondary Outcome Measures

Name	Time	Method
Presence of Adverse Events as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents	From time of signature of informed consent up to 15 months post the first dose of study treatment	The secondary endpoint of safety as assessed by the presence of adverse events and serious adverse events
Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents	From baseline up to 15 months post the first dose of study treatment	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
Presence of Abnormalities in Vital Signs as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents	From baseline up to 15 months post the first dose of study treatment	The secondary endpoint of safety as assessed by the presence of abnormal vital signs reported as adverse events
Duration of Response (DoR) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents	Up to approximately 54 months (through the database cutoff date of 18-Jul-2023).	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
Disease Control (DC) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents	Up to approximately 54 months (through the database cutoff date of 18-Jul-2023).	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.
Progression-Free Survival (PFS) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents	Up to approximately 54 months (through the database cutoff date of 18-Jul-2023).	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
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 rate at 12 months after randomization.	PFS-12 was defined as the percentage of participants who were alive and progression free at 12 months after randomization.
Overall Survival (OS) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents	From time of randomization until death due to any cause. Assessed through the database cutoff date of 18-Jul-2023).	OS was defined as the time from the date of randomization until death due to any cause.
Pharmacokinetics of Durvalumab Alone and in Combination With Novel Agents	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	Geometric mean serum concentrations of durvalumab (μg/mL) were reported for each time point where data warrant, as appropriate.
Pharmacokinetics of Novel Agents in Combination With Durvalumab	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	Geometric mean serum concentrations of oleclumab (μg/mL) and monalizumab (μg/mL) were reported for each time point where data warrant, as appropriate.
Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents	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	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.
Presence of Detectable Anti-Drug Antibody (ADA) Response to Novel Agents in Combination With Durvalumab	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	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.

Trial Locations

Locations (1)

Research Site; 🇨🇳 Taichung, Taiwan