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Completed

NCT Number: NCT03822351

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

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.

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Key information

Conditions

Stage III Non-small Cell Lung Cancer Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms Unresectable

Age range

18 year–99 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Research Site, Edmonton, Alberta, Canada

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About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Main Inclusion Criteria:

  • Written informed consent and any locally required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluation
  • Age 18 years or older
  • Body weight ≥ 35 kg
  • Subjects must have histologically or cytologically documented NSCLC who present with locally advanced, unresectable, Stage III disease
  • Subjects must have completed, without progressing, definitive cCRT within 42 days prior to being randomized into the study
  • Provision of tumor tissue sample, when available, from original diagnosis obtained before initiation of chemoradiotherapy
  • Life expectancy ≥ 12 weeks
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Subjects must have at least one previously irradiated tumor lesion that can be measured by RECIST v1.1

Main Exclusion Criteria:

  • Mixed small cell and non-small cell lung cancer histology
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of study drug
  • Prior exposure to any anti-PD1, anti-PD-L1, or anti-CTLA4 antibody for treatment of NSCLC
  • Subjects with history of ≥ Grade 2 pneumonitis from prior chemoradiation therapy
  • Subjects with a history of venous thrombosis within the past 3 months
  • Subjects with history of myocardial infarction, transient ischemic attack, or stroke in the past 6 months
  • Congestive heart failure
  • Active or prior documented autoimmune or inflammatory disorders
  • History of active primary immunodeficiency
  • Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
  • History of allogenic organ transplantation
  • QTcF interval ≥ 470 ms
  • History of another primary malignancy
  • 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]
  • Females who are pregnant, lactating, or intend to become pregnant during their participation in the study

Treatment and study plan

Durvalumab + Oleclumab

Drug

Durvalumab + Oleclumab

Other names: Durvalumab (MEDI-4736), Oleclumab (MEDI-9447)

Durvalumab

Drug

Durvalumab

Other names: Durvalumab (MEDI-4736)

Durvalumab + Monalizumab

Drug

Durvalumab + Monalizumab

Other names: Durvalumab (MEDI-4736), Monalizumab (IPH2201)

Primary outcomes

  1. Objective Response (OR) Rate as a Measure of Antitumor Activity of Durvalumab Alone vs Durvalumab in Combination With Novel Agents

    Time frame: 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 outcomes

  1. Presence of Adverse Events as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents

    Time frame: 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

  2. Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents

    Time frame: 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

  3. Presence of Abnormalities in Vital Signs as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents

    Time frame: 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

  4. Duration of Response (DoR) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents

    Time frame: 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

  5. Disease Control (DC) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents

    Time frame: 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.

  6. Progression-Free Survival (PFS) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents

    Time frame: 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

  7. 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: 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.

  8. Overall Survival (OS) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents

    Time frame: 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.

  9. Pharmacokinetics of Durvalumab Alone and in Combination With Novel Agents

    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

    Geometric mean serum concentrations of durvalumab (μg/mL) were reported for each time point where data warrant, as appropriate.

  10. Pharmacokinetics of Novel Agents in Combination With Durvalumab

    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

    Geometric mean serum concentrations of oleclumab (μg/mL) and monalizumab (μg/mL) were reported for each time point where data warrant, as appropriate.

  11. Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents

    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

    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.

  12. Presence of Detectable Anti-Drug Antibody (ADA) Response to Novel Agents in Combination With Durvalumab

    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

    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.

Sponsors and collaborators

Lead sponsor

MedImmune LLC

Industry

Registry information

Official study 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)

Acronym: COAST

Important dates

Study start
2018
Primary completion
2023
Study completion
2023
First posted
Jan 30, 2019
Registry last updated
Oct 8, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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