Stage III Non-small Cell Lung Cancer, Unresectable
Conditions
Keywords
Locally Advanced NSCLC, Non-small Cell Lung Cancer, Cancer, Lung, Unresectable, Stage III
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).
Interventions
DRUGDurvalumab + Oleclumab
Durvalumab + Oleclumab
DRUGDurvalumab
Durvalumab
DRUGDurvalumab + Monalizumab
Durvalumab + Monalizumab
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
At study onset subjects will be randomized equally to all study treatment arms open for enrollment and will remain on study treatment for up to 12 months. Study treatment will be discontinued upon disease progression, unacceptable toxicity, or other reason. The treatment arms are Control Arm, Arm A and Arm B.
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion 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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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. |
| 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. |
Countries
Canada, France, Hong Kong, Italy, Poland, Portugal, Spain, Taiwan, United States
Participant flow
Recruitment details
The first participant was randomized into the study on 3 January 2019 and the last participant was randomized on 6 July 2020.
Participants by arm
| Arm | Count |
|---|---|
| Control Arm (Durvalumab Monotherapy) Durvalumab 1500 mg IV monotherapy Q4W | 67 |
| Arm A (Durvalumab + Oleclumab) Durvalumab 1500 mg IV Q4W + Oleclumab 3000 mg IV (Q2W for cycles 1 and 2, then Q4W starting cycle 3) | 60 |
| Arm B (Durvalumab + Monalizumab) Durvalumab 1500 mg IV Q4W + Monalizumab 750 mg IV Q2W | 62 |
| Total | 189 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 27 | 23 | 24 |
| Overall Study | Lost to Follow-up | 6 | 2 | 1 |
| Overall Study | Not Treated | 1 | 1 | 1 |
| Overall Study | Progressive Disease | 2 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 10 | 4 | 6 |
Baseline characteristics
| Characteristic | Arm A (Durvalumab + Oleclumab) | Arm B (Durvalumab + Monalizumab) | Control Arm (Durvalumab Monotherapy) | Total |
|---|---|---|---|---|
| Age, Continuous | 63.8 years STANDARD_DEVIATION 9.5 | 64.4 years STANDARD_DEVIATION 9.2 | 65.5 years STANDARD_DEVIATION 8.9 | 64.6 years STANDARD_DEVIATION 9.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 3 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 56 Participants | 59 Participants | 63 Participants | 178 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 5 Participants | 5 Participants | 14 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants | 2 Participants | 1 Participants | 8 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 47 Participants | 55 Participants | 57 Participants | 159 Participants |
| Region of Enrollment Canada | 2 Participants | 1 Participants | 3 Participants | 6 Participants |
| Region of Enrollment France | 19 Participants | 5 Participants | 15 Participants | 39 Participants |
| Region of Enrollment Hong-Kong | 2 Participants | 3 Participants | 1 Participants | 6 Participants |
| Region of Enrollment Italy | 3 Participants | 3 Participants | 0 Participants | 6 Participants |
| Region of Enrollment Portugal | 0 Participants | 3 Participants | 3 Participants | 6 Participants |
| Region of Enrollment Spain | 12 Participants | 22 Participants | 19 Participants | 53 Participants |
| Region of Enrollment Taiwan | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Region of Enrollment United States | 22 Participants | 24 Participants | 25 Participants | 71 Participants |
| Sex: Female, Male Female | 18 Participants | 20 Participants | 22 Participants | 60 Participants |
| Sex: Female, Male Male | 42 Participants | 42 Participants | 45 Participants | 129 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 27 / 66 | 23 / 59 | 24 / 61 |
| other Total, other adverse events | 61 / 66 | 52 / 59 | 58 / 61 |
| serious Total, serious adverse events | 23 / 66 | 20 / 59 | 17 / 61 |
Outcome results
Primary
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
Population: The Intent-to-treat (ITT) population included participants who were randomized and were analyzed according to their randomized treatment group
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Arm (Durvalumab Monotherapy) | Objective Response (OR) Rate as a Measure of Antitumor Activity of Durvalumab Alone vs Durvalumab in Combination With Novel Agents | 23.9 Percentage of Participants |
| Arm A (Durvalumab + Oleclumab) | Objective Response (OR) Rate as a Measure of Antitumor Activity of Durvalumab Alone vs Durvalumab in Combination With Novel Agents | 35.0 Percentage of Participants |
| Arm B (Durvalumab + Monalizumab) | Objective Response (OR) Rate as a Measure of Antitumor Activity of Durvalumab Alone vs Durvalumab in Combination With Novel Agents | 40.3 Percentage of Participants |
Secondary
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).
Population: The Intent-to-treat (ITT) population included participants who were randomized and were analyzed according to their randomized treatment group
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Arm (Durvalumab Monotherapy) | Disease Control (DC) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents | 58.2 Percentage of Participants |
| Arm A (Durvalumab + Oleclumab) | Disease Control (DC) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents | 80.0 Percentage of Participants |
| Arm B (Durvalumab + Monalizumab) | Disease Control (DC) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents | 79.0 Percentage of Participants |
Secondary
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
Time frame: Up to approximately 54 months (through the database cutoff date of 18-Jul-2023).
Population: The Intent-to-treat (ITT) population included participants who were randomized and were analyzed according to their randomized treatment group. Only participants with an objective response were included in the DoR analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control Arm (Durvalumab Monotherapy) | Duration of Response (DoR) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents | NA Months |
| Arm A (Durvalumab + Oleclumab) | Duration of Response (DoR) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents | 29.9 Months |
| Arm B (Durvalumab + Monalizumab) | Duration of Response (DoR) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents | 23.0 Months |
Secondary
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).
Population: The Intent-to-treat (ITT) population included participants who were randomized and were analyzed according to their randomized treatment group
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control Arm (Durvalumab Monotherapy) | Overall Survival (OS) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents | 40.9 Months |
| Arm A (Durvalumab + Oleclumab) | Overall Survival (OS) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents | NA Months |
| Arm B (Durvalumab + Monalizumab) | Overall Survival (OS) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents | NA Months |
Secondary
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
Population: The PK-evaluable durvalumab population included participants from the As-treated population who had a non-missing baseline PK durvalumab concentration and at least one non-missing post-baseline PK durvalumab concentration
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Control Arm (Durvalumab Monotherapy) | Pharmacokinetics of Durvalumab Alone and in Combination With Novel Agents | Cycle 1 Day 1: End of Infusion | 318.0 Micrograms per milliliter | Geometric Coefficient of Variation 199.6 |
| Control Arm (Durvalumab Monotherapy) | Pharmacokinetics of Durvalumab Alone and in Combination With Novel Agents | Cycle 2 Day 1: Pre-Dose | 59.7 Micrograms per milliliter | Geometric Coefficient of Variation 58.6 |
| Control Arm (Durvalumab Monotherapy) | Pharmacokinetics of Durvalumab Alone and in Combination With Novel Agents | Cycle 11 Day 1: Pre-Dose | 156.7 Micrograms per milliliter | Geometric Coefficient of Variation 50 |
| Control Arm (Durvalumab Monotherapy) | Pharmacokinetics of Durvalumab Alone and in Combination With Novel Agents | Cycle 7 Day 1: Pre-Dose | 151.6 Micrograms per milliliter | Geometric Coefficient of Variation 37.7 |
| Arm A (Durvalumab + Oleclumab) | Pharmacokinetics of Durvalumab Alone and in Combination With Novel Agents | Cycle 11 Day 1: Pre-Dose | 146.5 Micrograms per milliliter | Geometric Coefficient of Variation 91.3 |
| Arm A (Durvalumab + Oleclumab) | Pharmacokinetics of Durvalumab Alone and in Combination With Novel Agents | Cycle 1 Day 1: End of Infusion | 277.4 Micrograms per milliliter | Geometric Coefficient of Variation 316.1 |
| Arm A (Durvalumab + Oleclumab) | Pharmacokinetics of Durvalumab Alone and in Combination With Novel Agents | Cycle 2 Day 1: Pre-Dose | 68.0 Micrograms per milliliter | Geometric Coefficient of Variation 49.9 |
| Arm A (Durvalumab + Oleclumab) | Pharmacokinetics of Durvalumab Alone and in Combination With Novel Agents | Cycle 7 Day 1: Pre-Dose | 127.9 Micrograms per milliliter | Geometric Coefficient of Variation 66.4 |
| Arm B (Durvalumab + Monalizumab) | Pharmacokinetics of Durvalumab Alone and in Combination With Novel Agents | Cycle 2 Day 1: Pre-Dose | 74.3 Micrograms per milliliter | Geometric Coefficient of Variation 40.7 |
| Arm B (Durvalumab + Monalizumab) | Pharmacokinetics of Durvalumab Alone and in Combination With Novel Agents | Cycle 11 Day 1: Pre-Dose | 172.4 Micrograms per milliliter | Geometric Coefficient of Variation 40.4 |
| Arm B (Durvalumab + Monalizumab) | Pharmacokinetics of Durvalumab Alone and in Combination With Novel Agents | Cycle 1 Day 1: End of Infusion | 223.7 Micrograms per milliliter | Geometric Coefficient of Variation 1272 |
| Arm B (Durvalumab + Monalizumab) | Pharmacokinetics of Durvalumab Alone and in Combination With Novel Agents | Cycle 7 Day 1: Pre-Dose | 176.5 Micrograms per milliliter | Geometric Coefficient of Variation 45.6 |
Secondary
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
Population: The PK-evaluable oleclumab/monalizumab population included participants from the As-treated population who had a non-missing baseline PK oleclumab/monalizumab concentration and at least one non-missing post-baseline PK oleclumab/monalizumab concentration
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Control Arm (Durvalumab Monotherapy) | Pharmacokinetics of Novel Agents in Combination With Durvalumab | Cycle 7 Day 1: Pre-Dose | 124.5 Micrograms per milliliter | Geometric Coefficient of Variation 109 |
| Control Arm (Durvalumab Monotherapy) | Pharmacokinetics of Novel Agents in Combination With Durvalumab | Cycle 1 Day 1: End of Infusion | 581.6 Micrograms per milliliter | Geometric Coefficient of Variation 210.5 |
| Control Arm (Durvalumab Monotherapy) | Pharmacokinetics of Novel Agents in Combination With Durvalumab | Cycle 11 Day 1: Pre-Dose | 132.0 Micrograms per milliliter | Geometric Coefficient of Variation 166.8 |
| Control Arm (Durvalumab Monotherapy) | Pharmacokinetics of Novel Agents in Combination With Durvalumab | Cycle 2 Day 1: Pre-Dose | 216.4 Micrograms per milliliter | Geometric Coefficient of Variation 58.6 |
| Arm A (Durvalumab + Oleclumab) | Pharmacokinetics of Novel Agents in Combination With Durvalumab | Cycle 11 Day 1: Pre-Dose | 196.2 Micrograms per milliliter | Geometric Coefficient of Variation 48.7 |
| Arm A (Durvalumab + Oleclumab) | Pharmacokinetics of Novel Agents in Combination With Durvalumab | Cycle 2 Day 1: Pre-Dose | 102.6 Micrograms per milliliter | Geometric Coefficient of Variation 39.2 |
| Arm A (Durvalumab + Oleclumab) | Pharmacokinetics of Novel Agents in Combination With Durvalumab | Cycle 7 Day 1: Pre-Dose | 194.5 Micrograms per milliliter | Geometric Coefficient of Variation 33.8 |
| Arm A (Durvalumab + Oleclumab) | Pharmacokinetics of Novel Agents in Combination With Durvalumab | Cycle 1 Day 1: End of Infusion | 160.0 Micrograms per milliliter | Geometric Coefficient of Variation 286.4 |
Secondary
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
Population: The As-treated population included all participants who receive any IP. Participants were analyzed according to the treatment they received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Control Arm (Durvalumab Monotherapy) | Presence of Abnormalities in Vital Signs as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Pyrexia | 6 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Abnormalities in Vital Signs as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Palpitations | 0 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Abnormalities in Vital Signs as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Hypertension | 3 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Abnormalities in Vital Signs as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Hypotension | 2 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Abnormalities in Vital Signs as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Tachycardia | 1 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Abnormalities in Vital Signs as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Palpitations | 0 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Abnormalities in Vital Signs as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Hypertension | 3 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Abnormalities in Vital Signs as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Hypotension | 0 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Abnormalities in Vital Signs as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Pyrexia | 8 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Abnormalities in Vital Signs as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Tachycardia | 2 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Abnormalities in Vital Signs as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Tachycardia | 2 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Abnormalities in Vital Signs as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Pyrexia | 10 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Abnormalities in Vital Signs as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Hypertension | 0 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Abnormalities in Vital Signs as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Palpitations | 1 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Abnormalities in Vital Signs as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Hypotension | 3 Participants |
Secondary
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
Population: The As-treated population included all participants who receive any IP. Participants were analyzed according to the treatment they received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Control Arm (Durvalumab Monotherapy) | Presence of Adverse Events as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any TEAEs | 65 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Adverse Events as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any serious TEAEs | 23 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Adverse Events as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any TEAEs | 57 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Adverse Events as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any serious TEAEs | 20 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Adverse Events as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any TEAEs | 61 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Adverse Events as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any serious TEAEs | 17 Participants |
Secondary
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
Population: The As-treated population included all participants who receive any IP. Participants were analyzed according to the treatment they received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Control Arm (Durvalumab Monotherapy) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Alanine Aminostransferase (U/L) toxicities | 1 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Hypocalcemia (corrected) (mg/dL) toxicities | 1 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Creatinine Clearance Rate (mL/min) toxicities | 2 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Albumin (g/dL) toxicities | 2 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Hemoglobin increased (g/dL) toxicities | 3 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Creatinine (mg/dL) toxicities | 1 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Amylase (U/L) toxicities | 1 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Aspartate Aminotransferase (U/L) toxicities | 1 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Hypokalemia (mEq/L) toxicities | 1 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Lymphocyte count increased (10^3/uL) toxicities | 19 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Lipase (U/L) toxicities | 1 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Hyperkalemia (mEq/L) toxicities | 0 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Platelet count decreased (10^3/uL) toxicities | 1 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Hypernatremia (mEq/L) toxicities | 1 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Gamma Glutamyl Transferase (U/L) toxicities | 1 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Hyperkalemia (mEq/L) toxicities | 0 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Lipase (U/L) toxicities | 4 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Hemoglobin increased (g/dL) toxicities | 0 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Lymphocyte count increased (10^3/uL) toxicities | 11 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Platelet count decreased (10^3/uL) toxicities | 0 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Alanine Aminostransferase (U/L) toxicities | 0 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Albumin (g/dL) toxicities | 0 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Aspartate Aminotransferase (U/L) toxicities | 0 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Creatinine (mg/dL) toxicities | 0 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Creatinine Clearance Rate (mL/min) toxicities | 1 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Gamma Glutamyl Transferase (U/L) toxicities | 0 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Amylase (U/L) toxicities | 0 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Hypokalemia (mEq/L) toxicities | 0 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Hypocalcemia (corrected) (mg/dL) toxicities | 0 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Hypernatremia (mEq/L) toxicities | 2 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Platelet count decreased (10^3/uL) toxicities | 0 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Hypernatremia (mEq/L) toxicities | 1 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Gamma Glutamyl Transferase (U/L) toxicities | 0 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Lymphocyte count increased (10^3/uL) toxicities | 11 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Hypocalcemia (corrected) (mg/dL) toxicities | 0 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Hyperkalemia (mEq/L) toxicities | 2 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Hemoglobin increased (g/dL) toxicities | 0 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Amylase (U/L) toxicities | 2 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Aspartate Aminotransferase (U/L) toxicities | 1 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Albumin (g/dL) toxicities | 0 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Hypokalemia (mEq/L) toxicities | 1 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Creatinine (mg/dL) toxicities | 0 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Alanine Aminostransferase (U/L) toxicities | 0 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Lipase (U/L) toxicities | 2 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Clinically Significant Laboratory Values as a Measure of Safety and Tolerability of Durvalumab Alone and in Combination With Novel Agents | Participants with any Grade 3 or 4 Creatinine Clearance Rate (mL/min) toxicities | 0 Participants |
Secondary
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
Population: The durvalumab ADA-evaluable population included participants from the As-treated population who had a non-missing baseline durvalumab ADA result and at least one non-missing post-baseline durvalumab ADA result
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Control Arm (Durvalumab Monotherapy) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents | Treatment-emergent ADA positive (ADA incidence) | 1 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents | Treatment-boosted ADA | 0 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents | Persistently positive | 1 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents | ADA positive at any visit (ADA prevalence) | 3 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents | Treatment-induced ADA (positive post-baseline only) | 1 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents | ADA positive at baseline only | 2 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents | ADA positive post-baseline and positive at baseline | 0 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents | Transiently positive | 0 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents | ADA positive post-baseline and positive at baseline | 0 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents | Treatment-emergent ADA positive (ADA incidence) | 0 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents | ADA positive at any visit (ADA prevalence) | 1 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents | Transiently positive | 0 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents | Treatment-boosted ADA | 0 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents | Persistently positive | 0 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents | Treatment-induced ADA (positive post-baseline only) | 0 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents | ADA positive at baseline only | 1 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents | Treatment-induced ADA (positive post-baseline only) | 0 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents | ADA positive post-baseline and positive at baseline | 0 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents | Persistently positive | 0 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents | ADA positive at any visit (ADA prevalence) | 2 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents | ADA positive at baseline only | 2 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents | Treatment-emergent ADA positive (ADA incidence) | 0 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents | Transiently positive | 0 Participants |
| Arm B (Durvalumab + Monalizumab) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Durvalumab Alone and in Combination With Novel Agents | Treatment-boosted ADA | 0 Participants |
Secondary
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
Population: The oleclumab/monalizumab ADA-evaluable population included participants from the As-treated population who had a non-missing baseline oleclumab/monalizumab ADA result and at least one non-missing post-baseline oleclumab/monalizumab ADA result
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Control Arm (Durvalumab Monotherapy) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Novel Agents in Combination With Durvalumab | Treatment-boosted ADA | 0 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Novel Agents in Combination With Durvalumab | Treatment-induced ADA (positive post-baseline only) | 0 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Novel Agents in Combination With Durvalumab | ADA positive at baseline only | 0 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Novel Agents in Combination With Durvalumab | ADA positive at any visit (ADA prevalence) | 0 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Novel Agents in Combination With Durvalumab | Persistently positive | 0 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Novel Agents in Combination With Durvalumab | Treatment-emergent ADA positive (ADA incidence) | 0 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Novel Agents in Combination With Durvalumab | Transiently positive | 0 Participants |
| Control Arm (Durvalumab Monotherapy) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Novel Agents in Combination With Durvalumab | ADA positive post-baseline and positive at baseline | 0 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Novel Agents in Combination With Durvalumab | Transiently positive | 1 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Novel Agents in Combination With Durvalumab | Treatment-boosted ADA | 0 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Novel Agents in Combination With Durvalumab | Treatment-induced ADA (positive post-baseline only) | 1 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Novel Agents in Combination With Durvalumab | ADA positive at baseline only | 0 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Novel Agents in Combination With Durvalumab | Treatment-emergent ADA positive (ADA incidence) | 1 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Novel Agents in Combination With Durvalumab | ADA positive post-baseline and positive at baseline | 0 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Novel Agents in Combination With Durvalumab | Persistently positive | 0 Participants |
| Arm A (Durvalumab + Oleclumab) | Presence of Detectable Anti-Drug Antibody (ADA) Response to Novel Agents in Combination With Durvalumab | ADA positive at any visit (ADA prevalence) | 1 Participants |
Secondary
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.
Population: The Intent-to-treat (ITT) population included participants who were randomized and were analyzed according to their randomized treatment group
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Arm (Durvalumab Monotherapy) | Progression-Free Survival 12 Month Landmark Rate (PFS-12) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents | 37.6 Percentage of Participants |
| Arm A (Durvalumab + Oleclumab) | Progression-Free Survival 12 Month Landmark Rate (PFS-12) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents | 63.5 Percentage of Participants |
| Arm B (Durvalumab + Monalizumab) | Progression-Free Survival 12 Month Landmark Rate (PFS-12) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents | 73.2 Percentage of Participants |
Secondary
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).
Population: The Intent-to-treat (ITT) population included participants who were randomized and were analyzed according to their randomized treatment group
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control Arm (Durvalumab Monotherapy) | Progression-Free Survival (PFS) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents | 7.3 Months |
| Arm A (Durvalumab + Oleclumab) | Progression-Free Survival (PFS) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents | 21.1 Months |
| Arm B (Durvalumab + Monalizumab) | Progression-Free Survival (PFS) as a Measure of Efficacy of Durvalumab Alone vs Durvalumab in Combination With Novel Agents | 19.8 Months |