Non-Small-Cell Lung Carcinoma NSCLC
Conditions
Keywords
NSCLC, PD-L1, MEDI4736, Tremelimumab, PFS, OS
Brief summary
This is a randomized, open-label, multi-center, global, Phase III study to determine the efficacy and safety of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy versus platinum-based SoC chemotherapy in the first-line treatment of patients with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type locally advanced or metastatic NSCLC
Detailed description
Patients will be randomized in a 1:1:1 ratio to receive treatment with MEDI4736 + tremelimumab combination therapy, MEDI4736 monotherapy, or Standard of Care (SoC) therapy.
Interventions
BIOLOGICALMEDI4736 (Durvalumab)
BIOLOGICALMEDI4736 (Durvalumab)+Tremelimumab
Chemotherapy Agents
Chemotherapy Agents
Chemotherapy Agents
Chemotherapy Agents
Chemotherapy Agents
BIOLOGICALTremelimumab
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
For inclusion in the study, patients should fulfill the following criteria: * Aged at least 18 years * Documented evidence of Stage IV NSCLC * No sensitizing EGFR mutation or ALK rearrangement * No prior chemotherapy or any other systemic therapy for recurrent/metastatic NSCLC * World Health Organization (WHO) Performance Status of 0 or 1
Exclusion criteria
Patients should not enter the study if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs SoC Chemotherapy | From baseline (Day 1, Week 0) until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years). | The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique. |
| Progression-Free Survival (PFS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs SoC Chemotherapy | Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years). | The PFS per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) using blinded independent central review (BICR) assessments was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraw from randomized therapy or received another anti-cancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions (TLs) and an absolute increase of at least 5 millimeter (mm), taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| OS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs Durvalumab Monotherapy | From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years). | The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique. |
| OS; PD-L1 (TC >=1%) Analysis Set Population | From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years). | The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique. |
| OS; FAS Population | From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years). | The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique. |
| PFS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs Durvalumab Monotherapy | Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years). | The PFS per RECIST 1.1 using BICR assessments was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraw from randomized therapy or received another anti-cancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). The PD was defined as at least a 20% increase in the sum of diameters of TLs and an absolute increase of at least 5 mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique. |
| PFS; PD-L1 (TC >=1%) Analysis Set Population | Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years). | The PFS per RECIST 1.1 using BICR assessments was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraw from randomized therapy or received another anti-cancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). The PD was defined as at least a 20% increase in the sum of diameters of TLs and an absolute increase of at least 5 mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique. |
| PFS; FAS Population | Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years). | The PFS per RECIST 1.1 using BICR assessments was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraw from randomized therapy or received another anti-cancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). The PD was defined as at least a 20% increase in the sum of diameters of TLs and an absolute increase of at least 5 mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique. |
| Objective Response Rate (ORR); PD-L1 (TC >=25%) Analysis Set Population | Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years). | The ORR per RECIST 1.1 using BICR assessments was defined as the percentage of participants with at least 1 visit response of Complete Response (CR) or Partial Response (PR). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met). |
| ORR; PD-L1 (TC >=1%) Analysis Set Population | Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years). | The ORR per RECIST 1.1 using BICR assessments was defined as the percentage of participants with at least 1 visit response of CR or PR. The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met). |
| ORR; FAS Population | Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years). | The ORR per RECIST 1.1 using BICR assessments was defined as the percentage of participants with at least 1 visit response of CR or PR. The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met). |
| Duration of Response (DoR); PD-L1 (TC >=25%) Analysis Set Population | Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years). | The DoR per RECIST 1.1 using BICR assessments was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (ie, date of PFS event or censoring - date of first response + 1). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met). |
| DoR; PD-L1 (TC >=1%) Analysis Set Population | Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years). | The DoR per RECIST 1.1 using BICR assessments was defined as the time from the date of first documented response (CR or PR) until the first date of documented progression or death in the absence of disease progression (ie, date of PFS event or censoring - date of first response + 1). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met). |
| DoR; FAS Population | Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years). | The DoR per RECIST 1.1 using BICR assessments was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (ie, date of PFS event or censoring - date of first response + 1). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met). |
| Percentage of Participants Alive and Progression Free at 12 Months (APF12); PD-L1 (TC >=25%) Analysis Set Population | Tumour scans performed at baseline then every 6 weeks up to 12 months. | The APF12 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 using BICR assessments at 12 months after randomization. The PFS was calculated using the Kaplan-Meier technique. |
| Percentage of Participants APF12; PD-L1 (TC >=1%) Analysis Set Population | Tumour scans performed at baseline then every 6 weeks up to 12 months. | The APF12 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 using BICR assessments at 12 months after randomization. The PFS was calculated using the Kaplan-Meier technique. |
| Percentage of Participants APF12; FAS Population | Tumour scans performed at baseline then every 6 weeks up to 12 months. | The APF12 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 using BICR assessments at 12 months after randomization. The PFS was calculated using the Kaplan-Meier technique. |
| Time From Randomization to Second Progression (PFS2); PD-L1 (TC >=25%) Analysis Set Population | Tumour scans performed at baseline then every 6 weeks up to Week 48, then every 8 weeks thereafter until 1st progression. Disease then assessed per local practice until 2nd progression. Assessed up to data cut-off date (maximum of approximately 3 years). | The PFS2 was defined as the time from the date of randomization to the earliest of the progression events (subsequent to that used for the primary variable PFS and excluding any confirmation of progression scans performed for first progression) or death (ie, date of PFS2 event or censoring - date of randomization + 1). The second progression event was determined by local standard clinical practice which may have included any of the following: objective radiological imaging, symptomatic progression, or death. |
| PFS2; PD-L1 (TC >=1%) Analysis Set Population | Tumour scans performed at baseline then every 6 weeks up to Week 48, then every 8 weeks thereafter until 1st progression. Disease then assessed per local practice until 2nd progression. Assessed up to data cut-off date (maximum of approximately 3 years). | The PFS2 was defined as the time from the date of randomization to the earliest of the progression events (subsequent to that used for the primary variable PFS and excluding any confirmation of progression scans performed for first progression) or death (ie, date of PFS2 event or censoring - date of randomization + 1). The second progression event was determined by local standard clinical practice which may have included any of the following: objective radiological imaging, symptomatic progression, or death. |
| PFS2; FAS Population | Tumour scans performed at baseline then every 6 weeks up to Week 48, then every 8 weeks thereafter until 1st progression. Disease then assessed per local practice until 2nd progression. Assessed up to data cut-off date (maximum of approximately 3 years). | The PFS2 was defined as the time from the date of randomization to the earliest of the progression events (subsequent to that used for the primary variable PFS and excluding any confirmation of progression scans performed for first progression) or death (ie, date of PFS2 event or censoring - date of randomization + 1). The second progression event was determined by local standard clinical practice which may have included any of the following: objective radiological imaging, symptomatic progression, or death. |
| Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months | At baseline then every 4 weeks for the first 8 weeks relative to the date of randomization, then every 8 weeks until second progression/death, whichever comes first. Assessed up to 12 months. | Patient reported outcomes for 5 disease related symptoms was assessed using the EORTC QLQ-Core 30 (C30) items questionnaire (fatigue and appetite loss) and the EORTC QLQ-Lung Cancer module 13 (LC13) (dysponea, cough and chest pain). An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items with higher scores representing greater symptom severity. An improvement in symptoms were indicated by a negative change in score from baseline. A positive change in score from baseline indicated a deterioration of symptoms. A minimum clinically meaningful change is defined as an absolute change in the score from baseline of \>=10. |
| Serum Concentrations of Durvalumab | Pre-dose and within 1 hour after end of infusion at Week 0, 12 and 24, and at follow-up Month 3. | Blood samples were collected to determine the serum concentration of durvalumab. |
| Serum Concentrations of Tremelimumab | Pre-dose and within 1 hour after end of infusion at Week 0 and 12, and at follow-up Month 3. | Blood samples were collected to determine the serum concentration of tremelimumab. |
| Maximum Serum Concentration at Steady State (Cmax_ss) of Durvalumab | Within 1 hour after end of infusion on infusion day at Week 12. | Blood samples were collected to determine the Cmax\_ss of durvalumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods. |
| Cmax_ss of Tremelimumab | Within 1 hour after end of infusion on infusion day at Week 12. | Blood samples were collected to determine the Cmax\_ss of tremelimumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods. |
| Trough Serum Concentration at Steady State (Ctrough_ss) of Durvalumab | Pre-dose at Week 12. | Blood samples were collected to determine the Ctrough\_ss of durvalumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods. |
| Ctrough_ss of Tremelimumab | Pre-dose at Week 12. | Blood samples were collected to determine the Ctrough\_ss of tremelimumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods. |
| Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | At Weeks 0, 12, and 24; 3 and 6 months after last dose of study treatment. | Blood samples were measured for the presence of ADAs and ADA-neutralizing antibodies (nAb) for durvalumab using validated assays. Tiered analysis was performed to include screening, confirmatory, and titer assay components, and positive-negative cut points previously statistically determined from drug-naïve validation samples were employed. Immunogenicity results were analyzed by summarizing the number of participants who developed detectable ADAs against durvalumab. Persistently positive is defined as having at least 2 post-baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive is defined as having at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. |
| Number of Participants With ADA Response to Tremelimumab | At Weeks 0 and 12; 3 and 6 months after last dose of study treatment. | Blood samples were measured for the presence of ADAs and ADA-nAb for tremelimumab using validated assays. Tiered analysis was performed to include screening, confirmatory, and titer assay components, and positive-negative cut points previously statistically determined from drug-naïve validation samples were employed. Immunogenicity results were analyzed by summarizing the number of participants who developed detectable ADAs against tremelimumab. Persistently positive is defined as having at least 2 post-baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive is defined as having at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. |
Countries
Australia, Belgium, Canada, France, Germany, Hungary, Italy, Japan, Netherlands, Russia, South Korea, Spain, Switzerland, Taiwan, Thailand, United States, Vietnam
Contacts
STUDY_DIRECTORStuart McIntosh, MD
AstraZeneca, Alderley Park, Cheshire, UK
PRINCIPAL_INVESTIGATORNaiyer Rizvi, MD
Columbia University Medical Center, New York, NY, USA
Participant flow
Recruitment details
A total of 194 centers across 17 countries in Asia, Australia, Europe and North America randomized adults with epidermal growth factor receptor and anaplastic lymphoma kinase wild-type advanced or metastatic non-small cell lung cancer in this study. First participant was randomized on 14 August 2015 and final data cut-off date was 04 October 2018.
Pre-assignment details
A total of 1118 participants were randomized in a 1:1:1 ratio in stratified manner as per programmed cell death ligand 1 (PD-L1) tumor expression status (PD-L1 \[tumor cell (TC) \>=25%\] versus (Vs) PD-L1 \[TC \<25%\]) and histology (squamous Vs non-squamous) to receive durvalumab alone, durvalumab + tremelimumab, or standard of care (SoC) chemotherapy.
Participants by arm
| Arm | Count |
|---|---|
| Durvalumab Monotherapy Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met. | 374 |
| Durvalumab + Tremelimumab Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met. | 372 |
| SoC Chemotherapy Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met.
1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL.
2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only).
3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only).
4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted). | 372 |
| Total | 1,118 |
Baseline characteristics
| Characteristic | Total | SoC Chemotherapy | Durvalumab + Tremelimumab | Durvalumab Monotherapy |
|---|---|---|---|---|
| Age, Continuous | 63.7 years STANDARD_DEVIATION 9.74 | 63.6 years STANDARD_DEVIATION 9.36 | 64.3 years STANDARD_DEVIATION 9.52 | 63.2 years STANDARD_DEVIATION 10.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 34 Participants | 6 Participants | 13 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1083 Participants | 366 Participants | 358 Participants | 359 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 363 Participants | 120 Participants | 118 Participants | 125 Participants |
| Race/Ethnicity, Customized Black or African American | 10 Participants | 4 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 7 Participants | 3 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 735 Participants | 243 Participants | 249 Participants | 243 Participants |
| Sex: Female, Male Female | 346 Participants | 122 Participants | 106 Participants | 118 Participants |
| Sex: Female, Male Male | 772 Participants | 250 Participants | 266 Participants | 256 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 278 / 374 | 278 / 372 | 297 / 372 |
| other Total, other adverse events | 335 / 369 | 328 / 371 | 332 / 352 |
| serious Total, serious adverse events | 131 / 369 | 178 / 371 | 112 / 352 |
Outcome results
Primary
Overall Survival (OS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs SoC Chemotherapy
The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique.
Time frame: From baseline (Day 1, Week 0) until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).
Population: The PD-L1 (TC \>=25%) analysis set included subset of participants in the FAS whose PD-L1 status was PD-L1 (TC \>=25%) as defined by Ventana PD-L1 (SP263) assay (ie, \>=25% TCs expressing PD-L1 on the membrane). Comparison of durvalumab monotherapy Vs SoC and durvalumab + tremelimumab Vs SoC reporting groups were analysed for primary outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab Monotherapy | Overall Survival (OS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs SoC Chemotherapy | 16.3 months |
| Durvalumab + Tremelimumab | Overall Survival (OS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs SoC Chemotherapy | 11.9 months |
| SoC Chemotherapy | Overall Survival (OS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs SoC Chemotherapy | 12.9 months |
Comparison: Durvalumab Monotherapy Vs SoC Chemotherapyp-value: 0.03697.54% CI: [0.564, 1.019]Log Rank
Comparison: Durvalumab + Tremelimumab Vs SoC Chemotherapyp-value: 0.20298.77% CI: [0.611, 1.173]Log Rank
Primary
Progression-Free Survival (PFS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs SoC Chemotherapy
The PFS per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) using blinded independent central review (BICR) assessments was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraw from randomized therapy or received another anti-cancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions (TLs) and an absolute increase of at least 5 millimeter (mm), taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique.
Time frame: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Population: The PD-L1 (TC \>=25%) analysis set included the subset of participants in the FAS whose PD-L1 status was PD-L1 (TC \>=25%) as defined by the Ventana PD-L1 (SP263) assay (ie, \>=25% TCs expressing PD-L1 on the membrane). Comparison of durvalumab + tremelimumab Vs SoC chemotherapy reporting groups were analysed for the primary outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab Monotherapy | Progression-Free Survival (PFS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs SoC Chemotherapy | 3.9 months |
| Durvalumab + Tremelimumab | Progression-Free Survival (PFS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs SoC Chemotherapy | 5.4 months |
Comparison: Durvalumab + Tremelimumab Vs SoC Chemotherapyp-value: 0.70599.5% CI: [0.722, 1.534]Log Rank
Secondary
Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months
Patient reported outcomes for 5 disease related symptoms was assessed using the EORTC QLQ-Core 30 (C30) items questionnaire (fatigue and appetite loss) and the EORTC QLQ-Lung Cancer module 13 (LC13) (dysponea, cough and chest pain). An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items with higher scores representing greater symptom severity. An improvement in symptoms were indicated by a negative change in score from baseline. A positive change in score from baseline indicated a deterioration of symptoms. A minimum clinically meaningful change is defined as an absolute change in the score from baseline of \>=10.
Time frame: At baseline then every 4 weeks for the first 8 weeks relative to the date of randomization, then every 8 weeks until second progression/death, whichever comes first. Assessed up to 12 months.
Population: The PD-L1 (TC \>=25%) analysis set included the subset of participants in the FAS whose PD-L1 status was PD-L1 (TC \>=25%) as defined by the Ventana PD-L1 (SP263) assay (ie, \>=25% TC expressing PD-L1 on the membrane).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Durvalumab Monotherapy | Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months | EORTC QLQ-LC13: Cough | -11.4 units on a scale | Standard Error 1.88 |
| Durvalumab Monotherapy | Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months | EORTC QLQ-LC13: Dyspnoea | 2.3 units on a scale | Standard Error 1.51 |
| Durvalumab Monotherapy | Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months | EORTC QLQ-C30: Fatigue | 1.2 units on a scale | Standard Error 1.83 |
| Durvalumab Monotherapy | Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months | EORTC QLQ-C30: Appetite loss | -3.9 units on a scale | Standard Error 2.24 |
| Durvalumab Monotherapy | Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months | EORTC QLQ-LC13: Chest pain | 0.1 units on a scale | Standard Error 1.71 |
| Durvalumab + Tremelimumab | Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months | EORTC QLQ-LC13: Dyspnoea | 0.8 units on a scale | Standard Error 1.6 |
| Durvalumab + Tremelimumab | Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months | EORTC QLQ-C30: Fatigue | -1.1 units on a scale | Standard Error 1.92 |
| Durvalumab + Tremelimumab | Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months | EORTC QLQ-C30: Appetite loss | 2.4 units on a scale | Standard Error 2.37 |
| Durvalumab + Tremelimumab | Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months | EORTC QLQ-LC13: Cough | -5.9 units on a scale | Standard Error 2.01 |
| Durvalumab + Tremelimumab | Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months | EORTC QLQ-LC13: Chest pain | 1.6 units on a scale | Standard Error 1.8 |
| SoC Chemotherapy | Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months | EORTC QLQ-LC13: Chest pain | 1.7 units on a scale | Standard Error 2.04 |
| SoC Chemotherapy | Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months | EORTC QLQ-LC13: Cough | -7.1 units on a scale | Standard Error 2.54 |
| SoC Chemotherapy | Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months | EORTC QLQ-C30: Fatigue | 10.6 units on a scale | Standard Error 2.34 |
| SoC Chemotherapy | Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months | EORTC QLQ-LC13: Dyspnoea | 5.6 units on a scale | Standard Error 1.9 |
| SoC Chemotherapy | Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months | EORTC QLQ-C30: Appetite loss | 8.0 units on a scale | Standard Error 2.83 |
Secondary
Cmax_ss of Tremelimumab
Blood samples were collected to determine the Cmax\_ss of tremelimumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods.
Time frame: Within 1 hour after end of infusion on infusion day at Week 12.
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the protocol for whom any post-dose data are available and who did not violate or deviate from the protocol in ways that would materially affect the PK analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Durvalumab Monotherapy | Cmax_ss of Tremelimumab | 24.8 mcg/mL | Standard Deviation 10.43 |
Secondary
Ctrough_ss of Tremelimumab
Blood samples were collected to determine the Ctrough\_ss of tremelimumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods.
Time frame: Pre-dose at Week 12.
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the protocol for whom any post-dose data are available and who did not violate or deviate from the protocol in ways that would materially affect the PK analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Durvalumab Monotherapy | Ctrough_ss of Tremelimumab | 4.9 mcg/mL | Standard Deviation 4.16 |
Secondary
DoR; FAS Population
The DoR per RECIST 1.1 using BICR assessments was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (ie, date of PFS event or censoring - date of first response + 1). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).
Time frame: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Population: The FAS included all randomized participants analyzed on an ITT basis. DoR is only analyzed for those participants with a response (including unconfirmed responses).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab Monotherapy | DoR; FAS Population | NA months |
| Durvalumab + Tremelimumab | DoR; FAS Population | NA months |
| SoC Chemotherapy | DoR; FAS Population | 4.3 months |
Secondary
DoR; PD-L1 (TC >=1%) Analysis Set Population
The DoR per RECIST 1.1 using BICR assessments was defined as the time from the date of first documented response (CR or PR) until the first date of documented progression or death in the absence of disease progression (ie, date of PFS event or censoring - date of first response + 1). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).
Time frame: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Population: The PD-L1 (TC \>=1%) analysis set included the subset of participants in the FAS whose PD-L1 status is PD-L1 (TC \>=1%) as defined by the Ventana PD-L1 (SP263) assay (ie, \>=1% TC expressing PD-L1 on the membrane). DoR is only analyzed for those participants with a response (including unconfirmed responses).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab Monotherapy | DoR; PD-L1 (TC >=1%) Analysis Set Population | NA months |
| Durvalumab + Tremelimumab | DoR; PD-L1 (TC >=1%) Analysis Set Population | NA months |
| SoC Chemotherapy | DoR; PD-L1 (TC >=1%) Analysis Set Population | 4.4 months |
Secondary
Duration of Response (DoR); PD-L1 (TC >=25%) Analysis Set Population
The DoR per RECIST 1.1 using BICR assessments was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (ie, date of PFS event or censoring - date of first response + 1). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).
Time frame: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Population: The PD-L1 (TC \>=25%) analysis set included the subset of participants in the FAS whose PD-L1 status was PD-L1 (TC \>=25%) as defined by the Ventana PD-L1 (SP263) assay (ie,\>=25% TC expressing PD-L1 on the membrane). DoR is only analyzed for those participants with a response (including unconfirmed responses).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab Monotherapy | Duration of Response (DoR); PD-L1 (TC >=25%) Analysis Set Population | NA months |
| Durvalumab + Tremelimumab | Duration of Response (DoR); PD-L1 (TC >=25%) Analysis Set Population | NA months |
| SoC Chemotherapy | Duration of Response (DoR); PD-L1 (TC >=25%) Analysis Set Population | 4.4 months |
Secondary
Maximum Serum Concentration at Steady State (Cmax_ss) of Durvalumab
Blood samples were collected to determine the Cmax\_ss of durvalumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods.
Time frame: Within 1 hour after end of infusion on infusion day at Week 12.
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the protocol for whom any post-dose data are available and who did not violate or deviate from the protocol in ways that would materially affect the PK analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Durvalumab Monotherapy | Maximum Serum Concentration at Steady State (Cmax_ss) of Durvalumab | 625.3 mcg/mL | Standard Deviation 453.8 |
| Durvalumab + Tremelimumab | Maximum Serum Concentration at Steady State (Cmax_ss) of Durvalumab | 506.1 mcg/mL | Standard Deviation 231.89 |
Secondary
Number of Participants With ADA Response to Tremelimumab
Blood samples were measured for the presence of ADAs and ADA-nAb for tremelimumab using validated assays. Tiered analysis was performed to include screening, confirmatory, and titer assay components, and positive-negative cut points previously statistically determined from drug-naïve validation samples were employed. Immunogenicity results were analyzed by summarizing the number of participants who developed detectable ADAs against tremelimumab. Persistently positive is defined as having at least 2 post-baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive is defined as having at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive.
Time frame: At Weeks 0 and 12; 3 and 6 months after last dose of study treatment.
Population: Safety analysis set included all participants who received at least 1 dose of study treatment. ADA evaluable population included participants who have non-missing baseline tremelimumab ADA and at least one non-missing post-baseline tremelimumab ADA result.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Durvalumab Monotherapy | Number of Participants With ADA Response to Tremelimumab | ADA positive at any time | 33 Participants |
| Durvalumab Monotherapy | Number of Participants With ADA Response to Tremelimumab | Treatment-emergent ADA positive | 28 Participants |
| Durvalumab Monotherapy | Number of Participants With ADA Response to Tremelimumab | ADA positive at baseline and post-baseline | 1 Participants |
| Durvalumab Monotherapy | Number of Participants With ADA Response to Tremelimumab | ADA positive at post-baseline only | 28 Participants |
| Durvalumab Monotherapy | Number of Participants With ADA Response to Tremelimumab | ADA positive at baseline only | 4 Participants |
| Durvalumab Monotherapy | Number of Participants With ADA Response to Tremelimumab | Treatment-boosted ADA | 0 Participants |
| Durvalumab Monotherapy | Number of Participants With ADA Response to Tremelimumab | Persistent positive | 25 Participants |
| Durvalumab Monotherapy | Number of Participants With ADA Response to Tremelimumab | Transient positive | 4 Participants |
| Durvalumab Monotherapy | Number of Participants With ADA Response to Tremelimumab | nAb positive at any visit | 25 Participants |
Secondary
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab
Blood samples were measured for the presence of ADAs and ADA-neutralizing antibodies (nAb) for durvalumab using validated assays. Tiered analysis was performed to include screening, confirmatory, and titer assay components, and positive-negative cut points previously statistically determined from drug-naïve validation samples were employed. Immunogenicity results were analyzed by summarizing the number of participants who developed detectable ADAs against durvalumab. Persistently positive is defined as having at least 2 post-baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive is defined as having at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive.
Time frame: At Weeks 0, 12, and 24; 3 and 6 months after last dose of study treatment.
Population: Safety analysis set included all participants who received at least 1 dose of study treatment. ADA evaluable population included participants who have non-missing durvalumab baseline ADA and at least one non-missing post-baseline durvalumab ADA result.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Durvalumab Monotherapy | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | Treatment-emergent ADA positive | 8 Participants |
| Durvalumab Monotherapy | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | Treatment-boosted ADA | 0 Participants |
| Durvalumab Monotherapy | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | ADA positive at post-baseline only | 8 Participants |
| Durvalumab Monotherapy | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | Persistent positive | 8 Participants |
| Durvalumab Monotherapy | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | ADA positive at baseline and post-baseline | 3 Participants |
| Durvalumab Monotherapy | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | Transient positive | 3 Participants |
| Durvalumab Monotherapy | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | ADA positive at baseline only | 6 Participants |
| Durvalumab Monotherapy | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | nAb positive at any visit | 2 Participants |
| Durvalumab Monotherapy | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | ADA positive at any time | 17 Participants |
| Durvalumab + Tremelimumab | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | nAb positive at any visit | 1 Participants |
| Durvalumab + Tremelimumab | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | ADA positive at any time | 14 Participants |
| Durvalumab + Tremelimumab | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | Treatment-emergent ADA positive | 8 Participants |
| Durvalumab + Tremelimumab | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | ADA positive at baseline and post-baseline | 1 Participants |
| Durvalumab + Tremelimumab | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | ADA positive at post-baseline only | 8 Participants |
| Durvalumab + Tremelimumab | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | ADA positive at baseline only | 5 Participants |
| Durvalumab + Tremelimumab | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | Treatment-boosted ADA | 0 Participants |
| Durvalumab + Tremelimumab | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | Persistent positive | 9 Participants |
| Durvalumab + Tremelimumab | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | Transient positive | 0 Participants |
Secondary
Objective Response Rate (ORR); PD-L1 (TC >=25%) Analysis Set Population
The ORR per RECIST 1.1 using BICR assessments was defined as the percentage of participants with at least 1 visit response of Complete Response (CR) or Partial Response (PR). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).
Time frame: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Population: The PD-L1 (TC \>=25%) analysis set included the subset of participants in the FAS whose PD-L1 status was PD-L1 (TC \>=25%) as defined by the Ventana PD-L1 (SP263) assay (ie, \>=25% TC expressing PD-L1 on the membrane).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab Monotherapy | Objective Response Rate (ORR); PD-L1 (TC >=25%) Analysis Set Population | 35.6 percentage of participants |
| Durvalumab + Tremelimumab | Objective Response Rate (ORR); PD-L1 (TC >=25%) Analysis Set Population | 34.4 percentage of participants |
| SoC Chemotherapy | Objective Response Rate (ORR); PD-L1 (TC >=25%) Analysis Set Population | 37.7 percentage of participants |
Comparison: Durvalumab Monotherapy Vs SoC Chemotherapyp-value: 0.69895% CI: [0.582, 1.437]Regression, Logistic
Comparison: Durvalumab + Tremelimumab Vs SoC Chemotherapyp-value: 0.53495% CI: [0.549, 1.363]Regression, Logistic
Comparison: Durvalumab + Tremelimumab Vs Durvalumab Monotherapyp-value: 0.8295% CI: [0.601, 1.496]Regression, Logistic
Secondary
ORR; FAS Population
The ORR per RECIST 1.1 using BICR assessments was defined as the percentage of participants with at least 1 visit response of CR or PR. The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).
Time frame: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Population: The FAS included all randomized participants analyzed on an ITT basis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab Monotherapy | ORR; FAS Population | 22.2 percentage of participants |
| Durvalumab + Tremelimumab | ORR; FAS Population | 24.7 percentage of participants |
| SoC Chemotherapy | ORR; FAS Population | 30.1 percentage of participants |
Comparison: Durvalumab Monotherapy Vs SoC Chemotherapyp-value: 0.01295% CI: [0.462, 0.908]Regression, Logistic
Comparison: Durvalumab + Tremelimumab Vs SoC Chemotherapyp-value: 0.09395% CI: [0.543, 1.048]Regression, Logistic
Comparison: Durvalumab + Tremelimumab Vs Durvalumab Monotherapyp-value: 0.40695% CI: [0.818, 1.647]Regression, Logistic
Secondary
ORR; PD-L1 (TC >=1%) Analysis Set Population
The ORR per RECIST 1.1 using BICR assessments was defined as the percentage of participants with at least 1 visit response of CR or PR. The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).
Time frame: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Population: The PD-L1 (TC \>=1%) analysis set included the subset of participants in the FAS whose PD-L1 status is PD-L1 (TC \>=1%) as defined by the Ventana PD-L1 (SP263) assay (ie, \>=1% TC expressing PD-L1 on the membrane).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab Monotherapy | ORR; PD-L1 (TC >=1%) Analysis Set Population | 26.5 percentage of participants |
| Durvalumab + Tremelimumab | ORR; PD-L1 (TC >=1%) Analysis Set Population | 25.3 percentage of participants |
| SoC Chemotherapy | ORR; PD-L1 (TC >=1%) Analysis Set Population | 33.6 percentage of participants |
Comparison: Durvalumab Monotherapy Vs SoC Chemotherapyp-value: 0.0595% CI: [0.48, 1]Regression, Logistic
Comparison: Durvalumab + Tremelimumab Vs SoC Chemotherapyp-value: 0.02995% CI: [0.464, 0.959]Regression, Logistic
Comparison: Durvalumab + Tremelimumab Vs Durvalumab Monotherapyp-value: 0.88795% CI: [0.661, 1.43]Regression, Logistic
Secondary
OS; FAS Population
The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique.
Time frame: From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).
Population: The FAS included all randomized participants analyzed on an ITT basis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab Monotherapy | OS; FAS Population | 12.3 months |
| Durvalumab + Tremelimumab | OS; FAS Population | 11.2 months |
| SoC Chemotherapy | OS; FAS Population | 11.8 months |
Comparison: Durvalumab Monotherapy Vs SoC Chemotherapyp-value: 0.60295% CI: [0.812, 1.128]Log Rank
Comparison: Durvalumab + Tremelimumab Vs SoC Chemotherapyp-value: 0.4395% CI: [0.794, 1.103]Log Rank
Comparison: Durvalumab + Tremelimumab Vs Durvalumab Monotherapyp-value: 0.80295% CI: [0.828, 1.157]Log Rank
Secondary
OS; PD-L1 (TC >=1%) Analysis Set Population
The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique.
Time frame: From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).
Population: The PD-L1 (TC \>=1%) analysis set included the subset of participants in the FAS whose PD-L1 status is PD-L1 (TC \>=1%) as defined by the Ventana PD-L1 (SP263) assay (ie, \>=1% TC expressing PD-L1 on the membrane).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab Monotherapy | OS; PD-L1 (TC >=1%) Analysis Set Population | 14.6 months |
| Durvalumab + Tremelimumab | OS; PD-L1 (TC >=1%) Analysis Set Population | 10.9 months |
| SoC Chemotherapy | OS; PD-L1 (TC >=1%) Analysis Set Population | 12.3 months |
Comparison: Durvalumab Monotherapy Vs SoC Chemotherapyp-value: 0.19495% CI: [0.725, 1.067]Log Rank
Comparison: Durvalumab + Tremelimumab Vs SoC Chemotherapyp-value: 0.95295% CI: [0.834, 1.213]Log Rank
Comparison: Durvalumab + Tremelimumab Vs Durvalumab Monotherapyp-value: 0.21895% CI: [0.931, 1.371]Log Rank
Secondary
OS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs Durvalumab Monotherapy
The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique.
Time frame: From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).
Population: The PD-L1 (TC \>=25%) analysis set included the subset of participants in the FAS whose PD-L1 status was PD-L1 (TC \>=25%) as defined by the Ventana PD-L1 (SP263) assay (ie, \>=25% TCs expressing PD-L1 on the membrane). Comparison of durvalumab + tremelimumab Vs durvalumab monotherapy reporting groups were analysed for the secondary outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab Monotherapy | OS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs Durvalumab Monotherapy | 16.3 months |
| Durvalumab + Tremelimumab | OS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs Durvalumab Monotherapy | 11.9 months |
| SoC Chemotherapy | OS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs Durvalumab Monotherapy | 12.9 months |
Comparison: Durvalumab + Tremelimumab Vs Durvalumab Monotherapyp-value: 0.52395% CI: [0.836, 1.421]Log Rank
Secondary
Percentage of Participants Alive and Progression Free at 12 Months (APF12); PD-L1 (TC >=25%) Analysis Set Population
The APF12 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 using BICR assessments at 12 months after randomization. The PFS was calculated using the Kaplan-Meier technique.
Time frame: Tumour scans performed at baseline then every 6 weeks up to 12 months.
Population: The PD-L1 (TC \>=25%) analysis set included the subset of participants in the FAS whose PD-L1 status was PD-L1 (TC \>=25%) as defined by the Ventana PD-L1 (SP263) assay (ie, \>=25% TC expressing PD-L1 on the membrane).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab Monotherapy | Percentage of Participants Alive and Progression Free at 12 Months (APF12); PD-L1 (TC >=25%) Analysis Set Population | 32.3 percentage of participants |
| Durvalumab + Tremelimumab | Percentage of Participants Alive and Progression Free at 12 Months (APF12); PD-L1 (TC >=25%) Analysis Set Population | 25.8 percentage of participants |
| SoC Chemotherapy | Percentage of Participants Alive and Progression Free at 12 Months (APF12); PD-L1 (TC >=25%) Analysis Set Population | 14.3 percentage of participants |
Secondary
Percentage of Participants APF12; FAS Population
The APF12 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 using BICR assessments at 12 months after randomization. The PFS was calculated using the Kaplan-Meier technique.
Time frame: Tumour scans performed at baseline then every 6 weeks up to 12 months.
Population: The FAS included all randomized participants analyzed on an ITT basis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab Monotherapy | Percentage of Participants APF12; FAS Population | 22.5 percentage of participants |
| Durvalumab + Tremelimumab | Percentage of Participants APF12; FAS Population | 19.8 percentage of participants |
| SoC Chemotherapy | Percentage of Participants APF12; FAS Population | 13.8 percentage of participants |
Secondary
Percentage of Participants APF12; PD-L1 (TC >=1%) Analysis Set Population
The APF12 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 using BICR assessments at 12 months after randomization. The PFS was calculated using the Kaplan-Meier technique.
Time frame: Tumour scans performed at baseline then every 6 weeks up to 12 months.
Population: The PD-L1 (TC \>=1%) analysis set included the subset of participants in the FAS whose PD-L1 status is PD-L1 (TC \>=1%) as defined by the Ventana PD-L1 (SP263) assay (ie, \>=1% TC expressing PD-L1 on the membrane).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab Monotherapy | Percentage of Participants APF12; PD-L1 (TC >=1%) Analysis Set Population | 27.0 percentage of participants |
| Durvalumab + Tremelimumab | Percentage of Participants APF12; PD-L1 (TC >=1%) Analysis Set Population | 20.4 percentage of participants |
| SoC Chemotherapy | Percentage of Participants APF12; PD-L1 (TC >=1%) Analysis Set Population | 14.9 percentage of participants |
Secondary
PFS2; FAS Population
The PFS2 was defined as the time from the date of randomization to the earliest of the progression events (subsequent to that used for the primary variable PFS and excluding any confirmation of progression scans performed for first progression) or death (ie, date of PFS2 event or censoring - date of randomization + 1). The second progression event was determined by local standard clinical practice which may have included any of the following: objective radiological imaging, symptomatic progression, or death.
Time frame: Tumour scans performed at baseline then every 6 weeks up to Week 48, then every 8 weeks thereafter until 1st progression. Disease then assessed per local practice until 2nd progression. Assessed up to data cut-off date (maximum of approximately 3 years).
Population: The FAS included all randomized participants analyzed on an ITT basis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab Monotherapy | PFS2; FAS Population | 9.3 months |
| Durvalumab + Tremelimumab | PFS2; FAS Population | 9.8 months |
| SoC Chemotherapy | PFS2; FAS Population | 10.1 months |
Comparison: Durvalumab Monotherapy Vs SoC Chemotherapyp-value: 0.66395% CI: [0.824, 1.131]Log Rank
Comparison: Durvalumab + Tremelimumab Vs SoC Chemotherapyp-value: 0.10395% CI: [0.746, 1.027]Log Rank
Secondary
PFS2; PD-L1 (TC >=1%) Analysis Set Population
The PFS2 was defined as the time from the date of randomization to the earliest of the progression events (subsequent to that used for the primary variable PFS and excluding any confirmation of progression scans performed for first progression) or death (ie, date of PFS2 event or censoring - date of randomization + 1). The second progression event was determined by local standard clinical practice which may have included any of the following: objective radiological imaging, symptomatic progression, or death.
Time frame: Tumour scans performed at baseline then every 6 weeks up to Week 48, then every 8 weeks thereafter until 1st progression. Disease then assessed per local practice until 2nd progression. Assessed up to data cut-off date (maximum of approximately 3 years).
Population: The PD-L1 (TC \>=1%) analysis set included the subset of participants in the FAS whose PD-L1 status is PD-L1 (TC \>=1%) as defined by the Ventana PD-L1 (SP263) assay (ie, \>=1% TC expressing PD-L1 on the membrane).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab Monotherapy | PFS2; PD-L1 (TC >=1%) Analysis Set Population | 10.6 months |
| Durvalumab + Tremelimumab | PFS2; PD-L1 (TC >=1%) Analysis Set Population | 9.4 months |
| SoC Chemotherapy | PFS2; PD-L1 (TC >=1%) Analysis Set Population | 10.5 months |
Comparison: Durvalumab Monotherapy Vs SoC Chemotherapyp-value: 0.25595% CI: [0.746, 1.08]Log Rank
Comparison: Durvalumab + Tremelimumab Vs SoC Chemotherapyp-value: 0.53495% CI: [0.787, 1.132]Log Rank
Secondary
PFS; FAS Population
The PFS per RECIST 1.1 using BICR assessments was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraw from randomized therapy or received another anti-cancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). The PD was defined as at least a 20% increase in the sum of diameters of TLs and an absolute increase of at least 5 mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique.
Time frame: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Population: The FAS included all randomized participants analyzed on an ITT basis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab Monotherapy | PFS; FAS Population | 2.8 months |
| Durvalumab + Tremelimumab | PFS; FAS Population | 2.9 months |
| SoC Chemotherapy | PFS; FAS Population | 5.4 months |
Comparison: Durvalumab Monotherapy Vs SoC Chemotherapyp-value: 0.01595% CI: [1.043, 1.475]Log Rank
Comparison: Durvalumab + Tremelimumab Vs SoC Chemotherapyp-value: 0.0195% CI: [1.054, 1.485]Log Rank
Comparison: Durvalumab + Tremelimumab Vs Durvalumab Monotherapyp-value: 0.98495% CI: [0.845, 1.179]Log Rank
Secondary
PFS; PD-L1 (TC >=1%) Analysis Set Population
The PFS per RECIST 1.1 using BICR assessments was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraw from randomized therapy or received another anti-cancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). The PD was defined as at least a 20% increase in the sum of diameters of TLs and an absolute increase of at least 5 mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique.
Time frame: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Population: The PD-L1 (TC \>=1%) analysis set included the subset of participants in the FAS whose PD-L1 status is PD-L1 (TC \>=1%) as defined by the Ventana PD-L1 (SP263) assay (ie, \>=1% TC expressing PD-L1 on the membrane).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab Monotherapy | PFS; PD-L1 (TC >=1%) Analysis Set Population | 3.6 months |
| Durvalumab + Tremelimumab | PFS; PD-L1 (TC >=1%) Analysis Set Population | 2.8 months |
| SoC Chemotherapy | PFS; PD-L1 (TC >=1%) Analysis Set Population | 5.5 months |
Comparison: Durvalumab Monotherapy Vs SoC Chemotherapyp-value: 0.38395% CI: [0.894, 1.339]Log Rank
Comparison: Durvalumab + Tremelimumab Vs SoC Chemotherapyp-value: 0.00195% CI: [1.136, 1.678]Log Rank
Comparison: Durvalumab + Tremelimumab Vs Durvalumab Monotherapyp-value: 0.13895% CI: [0.954, 1.403]Log Rank
Secondary
PFS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs Durvalumab Monotherapy
The PFS per RECIST 1.1 using BICR assessments was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraw from randomized therapy or received another anti-cancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). The PD was defined as at least a 20% increase in the sum of diameters of TLs and an absolute increase of at least 5 mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique.
Time frame: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Population: The PD-L1 (TC \>=25%) analysis set included subset of participants in the FAS whose PD-L1 status was PD-L1 (TC \>=25%) as defined by Ventana PD-L1 (SP263) assay (ie, \>=25% TCs expressing PD-L1 on the membrane). Comparison of durvalumab + tremelimumab Vs durvalumab and durvalumab Vs SoC reporting groups were analysed for secondary outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab Monotherapy | PFS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs Durvalumab Monotherapy | 4.7 months |
| Durvalumab + Tremelimumab | PFS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs Durvalumab Monotherapy | 3.9 months |
| SoC Chemotherapy | PFS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs Durvalumab Monotherapy | 5.4 months |
Comparison: Durvalumab Monotherapy Vs SoC Chemotherapyp-value: 0.32495% CI: [0.667, 1.143]Log Rank
Comparison: Durvalumab + Tremelimumab Vs Durvalumab Monotherapyp-value: 0.20795% CI: [0.911, 1.541]Log Rank
Secondary
Serum Concentrations of Durvalumab
Blood samples were collected to determine the serum concentration of durvalumab.
Time frame: Pre-dose and within 1 hour after end of infusion at Week 0, 12 and 24, and at follow-up Month 3.
Population: Pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of study treatment per the protocol for whom any post-dose data are available and who did not violate or deviate from the protocol in ways that would materially affect the PK analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Durvalumab Monotherapy | Serum Concentrations of Durvalumab | At Week 0: End of infusion | 484.5 microgram per milliliter (mcg/mL) | Standard Deviation 210.5 |
| Durvalumab Monotherapy | Serum Concentrations of Durvalumab | At Week 12: End of infusion | 625.3 microgram per milliliter (mcg/mL) | Standard Deviation 453.8 |
| Durvalumab Monotherapy | Serum Concentrations of Durvalumab | At Week 0: Pre-infusion | NA microgram per milliliter (mcg/mL) | — |
| Durvalumab Monotherapy | Serum Concentrations of Durvalumab | At Week 24: Pre-infusion | 163.0 microgram per milliliter (mcg/mL) | Standard Deviation 170.04 |
| Durvalumab Monotherapy | Serum Concentrations of Durvalumab | At Week 12: Pre-infusion | 139.5 microgram per milliliter (mcg/mL) | Standard Deviation 124.98 |
| Durvalumab Monotherapy | Serum Concentrations of Durvalumab | At follow-up Month 3 | 49.3 microgram per milliliter (mcg/mL) | Standard Deviation 132.54 |
| Durvalumab Monotherapy | Serum Concentrations of Durvalumab | At Week 24: End of infusion | 598.2 microgram per milliliter (mcg/mL) | Standard Deviation 344.52 |
| Durvalumab + Tremelimumab | Serum Concentrations of Durvalumab | At follow-up Month 3 | 41.4 microgram per milliliter (mcg/mL) | Standard Deviation 131.71 |
| Durvalumab + Tremelimumab | Serum Concentrations of Durvalumab | At Week 24: End of infusion | 553.2 microgram per milliliter (mcg/mL) | Standard Deviation 193.33 |
| Durvalumab + Tremelimumab | Serum Concentrations of Durvalumab | At Week 0: Pre-infusion | NA microgram per milliliter (mcg/mL) | — |
| Durvalumab + Tremelimumab | Serum Concentrations of Durvalumab | At Week 0: End of infusion | 444.3 microgram per milliliter (mcg/mL) | Standard Deviation 150.29 |
| Durvalumab + Tremelimumab | Serum Concentrations of Durvalumab | At Week 12: Pre-infusion | 140.8 microgram per milliliter (mcg/mL) | Standard Deviation 146.25 |
| Durvalumab + Tremelimumab | Serum Concentrations of Durvalumab | At Week 12: End of infusion | 506.1 microgram per milliliter (mcg/mL) | Standard Deviation 231.89 |
| Durvalumab + Tremelimumab | Serum Concentrations of Durvalumab | At Week 24: Pre-infusion | 197.0 microgram per milliliter (mcg/mL) | Standard Deviation 228.79 |
Secondary
Serum Concentrations of Tremelimumab
Blood samples were collected to determine the serum concentration of tremelimumab.
Time frame: Pre-dose and within 1 hour after end of infusion at Week 0 and 12, and at follow-up Month 3.
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the protocol for whom any post-dose data are available and who did not violate or deviate from the protocol in ways that would materially affect the PK analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Durvalumab Monotherapy | Serum Concentrations of Tremelimumab | At Week 0: Pre-infusion | NA mcg/mL | — |
| Durvalumab Monotherapy | Serum Concentrations of Tremelimumab | At Week 0: End of infusion | 22.6 mcg/mL | Standard Deviation 14.84 |
| Durvalumab Monotherapy | Serum Concentrations of Tremelimumab | At Week 12: Pre-infusion | 4.9 mcg/mL | Standard Deviation 4.16 |
| Durvalumab Monotherapy | Serum Concentrations of Tremelimumab | At Week 12: End of infusion | 24.8 mcg/mL | Standard Deviation 10.43 |
| Durvalumab Monotherapy | Serum Concentrations of Tremelimumab | At follow-up Month 3 | 0.5 mcg/mL | Standard Deviation 0.42 |
Secondary
Time From Randomization to Second Progression (PFS2); PD-L1 (TC >=25%) Analysis Set Population
The PFS2 was defined as the time from the date of randomization to the earliest of the progression events (subsequent to that used for the primary variable PFS and excluding any confirmation of progression scans performed for first progression) or death (ie, date of PFS2 event or censoring - date of randomization + 1). The second progression event was determined by local standard clinical practice which may have included any of the following: objective radiological imaging, symptomatic progression, or death.
Time frame: Tumour scans performed at baseline then every 6 weeks up to Week 48, then every 8 weeks thereafter until 1st progression. Disease then assessed per local practice until 2nd progression. Assessed up to data cut-off date (maximum of approximately 3 years).
Population: The PD-L1 (TC \>=25%) analysis set included the subset of participants in the FAS whose PD-L1 status was PD-L1 (TC \>=25%) as defined by the Ventana PD-L1 (SP263) assay (ie, \>=25% TC expressing PD-L1 on the membrane).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab Monotherapy | Time From Randomization to Second Progression (PFS2); PD-L1 (TC >=25%) Analysis Set Population | 12.7 months |
| Durvalumab + Tremelimumab | Time From Randomization to Second Progression (PFS2); PD-L1 (TC >=25%) Analysis Set Population | 10.9 months |
| SoC Chemotherapy | Time From Randomization to Second Progression (PFS2); PD-L1 (TC >=25%) Analysis Set Population | 10.4 months |
Comparison: Durvalumab Monotherapy Vs SoC Chemotherapyp-value: 0.0395% CI: [0.597, 0.975]Log Rank
Comparison: Durvalumab + Tremelimumab Vs SoC Chemotherapyp-value: 0.04595% CI: [0.606, 0.994]Log Rank
Secondary
Trough Serum Concentration at Steady State (Ctrough_ss) of Durvalumab
Blood samples were collected to determine the Ctrough\_ss of durvalumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods.
Time frame: Pre-dose at Week 12.
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the protocol for whom any post-dose data are available and who did not violate or deviate from the protocol in ways that would materially affect the PK analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Durvalumab Monotherapy | Trough Serum Concentration at Steady State (Ctrough_ss) of Durvalumab | 139.5 mcg/mL | Standard Deviation 124.98 |
| Durvalumab + Tremelimumab | Trough Serum Concentration at Steady State (Ctrough_ss) of Durvalumab | 140.8 mcg/mL | Standard Deviation 146.25 |