Non Small Cell Lung Carcinoma NSCLC
Conditions
Keywords
NSCLC, PDL1, TMB, MEDI4736, Durvalumab, Tremelimumab, OS
Brief summary
This is a randomized, open-label, multi-center, global, Phase III study to determine the efficacy and safety of durvalumab + tremelimumab combination therapy 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 advanced or metastatic NSCLC.
Detailed description
Patients will be randomized in a 1:1 to receive treatment with durvalumab + tremelimumab combination therapy or SoC therapy. The primary objective of this study is to assess the efficacy of combination treatment compared with SoC in terms of Overall Survival (OS) in patients.
Interventions
BIOLOGICALDurvalumab +Tremelimumab
Chemotherapy Agents
Chemotherapy Agents
Chemotherapy Agents
Chemotherapy Agent
Chemotherapy Agent
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 activating 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 * No Prior exposure to Immune Mediated Therapy (IMT), including, but not limited to, other antiCTLA4, antiPD1, anti PDL1,or antiPDL2 antibodies, excluding therapeutic anticancer vaccines
Exclusion criteria
Patients should not enter the study if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS); Global Cohort: Blood Tumor Mutational Burden (bTMB) ≥20 Mutations Per Megabase (Mut/Mb) Analysis Set | From baseline (Day 1, Week 0) until death due to any cause, assessed up to the Global cohort DCO date (a maximum of approximately 44 months). | 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 was 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; China Cohort: China Programmed Cell Death Ligand 1 (PD-L1) Negative NSCLC Analysis Set | From baseline (Day 1, Week 0) until death due to any cause, assessed up to the China cohort DCO date (a maximum of approximately 44 months). | 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 was 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| OS; Global Cohort: bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | From baseline (Day 1, Week 0) until death due to any cause, assessed up to the Global cohort DCO date (a maximum of approximately 44 months). | OS was defined as time from 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 time of analysis was censored based on last recorded date on which participant was known to be alive. bTMB ≥16 mut/Mb, bTMB ≥12 mut/Mb and bTMB \<20 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥16 mut/Mb, ≥12 mut/Mb and \<20 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay. PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue). bTMB non-evaluable analysis set included the subset of participants in FAS whose bTMB status at baseline could not be determined by the GuardantOMNI CDx assay or whose sample was not available. tTMB analysis sets are defined same as the bTMB analysis sets. |
| OS; Global and China Cohorts: FAS, PD-L1 Tumor Cell (TC) ≥25%, and PD-L1 TC ≥50% Analysis Sets | From baseline (Day 1, Week 0) until death due to any cause, assessed up to the Global or China cohort DCO dates, as applicable (a maximum of approximately 44 months) for each cohort. | The OS was defined as time from 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 was censored based on last recorded date on which participant was known to be alive. Global Cohort: The FAS included all randomized participants prior to the end of global recruitment. Any participants recruited in China, after global recruitment had ended, were not included in the FAS. China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses. PD-L1 TC ≥25% and PD-L1 TC ≥50% analysis sets included the subset of participants in the FAS whose PD-L1 status was TC ≥25% and TC ≥50% membrane expression in tumoral tissue, respectively at baseline as defined by the Ventana SP263 PD-L1 Assay. |
| Progression-Free Survival (PFS); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global cohort DCO date (approximately 44 months). | The PFS (per Response Evaluation Criteria in Solid Tumors, version 1.1 \[RECIST 1.1\] using Investigator assessments) was defined as the time from the date of randomization until the date of objective PD or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay. tTMB ≥14 mut/Mb, tTMB ≥12 mut/Mb, tTMB ≥10 mut/Mb and tTMB ≥8 mut/Mb analysis sets included the subset of participants in FAS whose tTMB status was ≥14 mut/Mb, ≥12 mut/Mb, ≥10 mut/Mb and ≥8 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay. |
| PFS; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global or China cohort DCO dates, as applicable (approximately 44 months) for each cohort. | PFS (per RECIST 1.1 using Investigator assessments) was defined as time from date of randomization until date of objective PD or death regardless of whether participant withdrew from randomized therapy or received another anticancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). PD-L1-negative analysis set included subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue). Global Cohort: FAS included all randomized participants prior to end of global recruitment. China Cohort: China FAS included all randomized participants in China cohort and were used for all China only efficacy analyses. PD-L1 TC ≥25% and PD-L1 TC ≥50% analysis sets included subset of participants in FAS whose PD-L1 status was TC ≥25% and TC ≥50% membrane expression in tumoral tissue, respectively at baseline as defined by the Ventana SP263 PD-L1 Assay. |
| OS at Months 12, 18 and 24; Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | Months 12, 18 and 24 | 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). bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay. |
| Objective Response Rate (ORR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global cohort DCO date (approximately 44 months). | The ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with at least 1 visit response of complete response (CR) or partial response (PR) prior to PD. bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay. tTMB ≥14 mut/Mb, tTMB ≥12 mut/Mb, tTMB ≥10 mut/Mb and tTMB ≥8 mut/Mb analysis sets included the subset of participants in FAS whose tTMB status was ≥14 mut/Mb, ≥12 mut/Mb, ≥10 mut/Mb and ≥8 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay. |
| ORR; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global or China cohort DCO dates, as applicable (approximately 44 months) for each cohort. | The ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with at least 1 visit response of CR or PR prior to PD. PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue). Global Cohort: The FAS included all randomized participants prior to the end of global recruitment. China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses. PD-L1 TC ≥25% and PD-L1 TC ≥50% analysis sets included the subset of participants in the FAS whose PD-L1 status was TC ≥25% and TC ≥50% membrane expression in tumoral tissue, respectively at baseline as defined by the Ventana SP263 PD-L1 Assay. |
| Duration of Response (DoR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global cohort DCO date (approximately 44 months). | DoR (per RECIST 1.1 using Investigator 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 PD (ie, date of PFS event or censoring - date of first response + 1). bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay. |
| DoR; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global or China cohort DCO dates, as applicable (approximately 44 months) for each cohort. | DoR (per RECIST 1.1 using Investigator 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 PD (ie, date of PFS event or censoring - date of first response + 1). PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue). Global Cohort: The FAS included all randomized participants prior to the end of global recruitment. China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses. |
| Alive and Progression-Free at 12 Months (APF12); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | 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 at 12 months from randomization (ie, PFS rate at 12 months). bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay. |
| APF12; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Tumour scans performed at baseline then every 6 weeks up to 12 months. | The APF12 was defined as the percentage of patients who were alive and progression free at 12 months from randomization (ie, PFS rate at 12 months). PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue). Global Cohort: The FAS included all randomized participants prior to the end of global recruitment. China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses. |
| Time From Randomization to Second Progression or Death (PFS2); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global cohort DCO date (approximately 44 months). | 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, or death (ie, date of PFS2 event or censoring - date of randomization + 1). bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay. |
| PFS2; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global or China cohort DCO dates, as applicable (approximately 44 months) for each cohort. | 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, or death (ie, date of PFS2 event or censoring - date of randomization + 1). PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue). Global Cohort: The FAS included all randomized participants prior to the end of global recruitment. China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses. |
| OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Months 12, 18 and 24 | 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). PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue). Global Cohort: The FAS included all randomized participants prior to the end of global recruitment. China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses. |
| Serum Concentrations of Durvalumab | Pre-dose and within 1 hour after end of infusion at Week 0 and 12; pre-dose on Week 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. |
| 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. ADA prevalence is defined as the percentage of participants with positive ADA result at any time, baseline or post-baseline. Treatment-emergent ADA is defined as the sum of treatment-induced ADA and treatment-boosted ADA. ADA incidence is the percentage of participants who were treatment-emergent ADA-positive. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted to \>=4 fold during the study period. 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 1 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. ADA prevalence is defined as the percentage of participants with positive ADA result at any time, baseline or post-baseline. Treatment-emergent ADA is defined as the sum of treatment-induced ADA and treatment-boosted ADA. ADA incidence is the percentage of participants who were treatment-emergent ADA-positive. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted to \>=4 fold during the study period. 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 1 post baseline ADA positive measurement and not fulfilling the conditions for persistently positive. |
Countries
Argentina, Brazil, Bulgaria, Chile, China, Denmark, Finland, Greece, Hong Kong, India, Israel, Japan, Malaysia, Mexico, Peru, Philippines, Poland, Portugal, Qatar, Romania, Russia, Saudi Arabia, Singapore, South Korea, Sweden, Turkey (Türkiye), Ukraine, United Kingdom, United States
Contacts
PRINCIPAL_INVESTIGATORGilberto de Castro
Faculdade de Medicina da Universidade de São Paulo
Participant flow
Recruitment details
A total of 192 centers across 29 countries in North America, Latin America, Asia, Europe and Gulf countries randomized adults with epidermal growth factor receptor and anaplastic lymphoma kinase wild-type advanced or metastatic non-small-cell lung cancer (NSCLC) in this study. First participant was enrolled on 03 November 2015 and final data cut-off (DCO) date was 24 June 2019 for Global cohort and 21 September 2020 for China cohort. SoC = standard of care
Pre-assignment details
823 participants in Global cohort and 160 participants in China cohort were randomized in 1:1 ratio to receive durvalumab + tremelimumab or SoC chemotherapy. China cohort comprised participants from mainland China (30 from Global cohort and 130 randomized after end of Global cohort recruitment). Thus, 953 unique participants were randomized in the study overall. Participants included in both cohorts for Started, Completed and Reasons for Not Completed are not double-counted for participant flow.
Participants by arm
| Arm | Count |
|---|---|
| All Participants: 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 to receive durvalumab 20 mg/kg Q4W, starting on Week 16 until objective PD, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or specific treatment discontinuation criteria were met. | 474 |
| All Participants: 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 objective PD, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or 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 participants 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 participants only).
4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous participants only; pemetrexed maintenance dose was permitted).
5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous participants only; pemetrexed maintenance dose was permitted). | 479 |
| Total | 953 |
Baseline characteristics
| Characteristic | All Participants: Durvalumab + Tremelimumab | Total | All Participants: SoC Chemotherapy |
|---|---|---|---|
| Age, Customized All participants <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized All participants >=65 years | 196 Participants | 431 Participants | 235 Participants |
| Age, Customized All participants Between 18 and 65 years | 278 Participants | 522 Participants | 244 Participants |
| Age, Customized China cohort <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized China cohort >=65 years | 25 Participants | 56 Participants | 31 Participants |
| Age, Customized China cohort Between 18 and 65 years | 53 Participants | 104 Participants | 51 Participants |
| Age, Customized Global cohort <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Global cohort >=65 years | 177 Participants | 387 Participants | 210 Participants |
| Age, Customized Global cohort Between 18 and 65 years | 233 Participants | 436 Participants | 203 Participants |
| Race/Ethnicity, Customized All participants American Indian or Alaska Native | 10 Participants | 22 Participants | 12 Participants |
| Race/Ethnicity, Customized All participants Asian | 150 Participants | 315 Participants | 165 Participants |
| Race/Ethnicity, Customized All participants Black or African American | 3 Participants | 10 Participants | 7 Participants |
| Race/Ethnicity, Customized All participants Hispanic or Latino | 50 Participants | 98 Participants | 48 Participants |
| Race/Ethnicity, Customized All participants Missing | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized All participants Not Hispanic or Latino | 423 Participants | 852 Participants | 429 Participants |
| Race/Ethnicity, Customized All participants Other | 3 Participants | 7 Participants | 4 Participants |
| Race/Ethnicity, Customized All participants White | 307 Participants | 596 Participants | 289 Participants |
| Race/Ethnicity, Customized China cohort American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized China cohort Asian | 78 Participants | 160 Participants | 82 Participants |
| Race/Ethnicity, Customized China cohort Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized China cohort Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized China cohort Missing | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized China cohort Not Hispanic or Latino | 78 Participants | 160 Participants | 82 Participants |
| Race/Ethnicity, Customized China cohort Other | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized China cohort White | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Global cohort American Indian or Alaska Native | 10 Participants | 22 Participants | 12 Participants |
| Race/Ethnicity, Customized Global cohort Asian | 86 Participants | 185 Participants | 99 Participants |
| Race/Ethnicity, Customized Global cohort Black or African American | 3 Participants | 10 Participants | 7 Participants |
| Race/Ethnicity, Customized Global cohort Hispanic or Latino | 50 Participants | 98 Participants | 48 Participants |
| Race/Ethnicity, Customized Global cohort Missing | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Global cohort Not Hispanic or Latino | 359 Participants | 722 Participants | 363 Participants |
| Race/Ethnicity, Customized Global cohort Other | 3 Participants | 7 Participants | 4 Participants |
| Race/Ethnicity, Customized Global cohort White | 307 Participants | 596 Participants | 289 Participants |
| Sex: Female, Male All participants Female | 127 Participants | 256 Participants | 129 Participants |
| Sex: Female, Male All participants Male | 347 Participants | 697 Participants | 350 Participants |
| Sex: Female, Male China cohort Female | 18 Participants | 43 Participants | 25 Participants |
| Sex: Female, Male China cohort Male | 60 Participants | 117 Participants | 57 Participants |
| Sex: Female, Male Global cohort Female | 113 Participants | 221 Participants | 108 Participants |
| Sex: Female, Male Global cohort Male | 297 Participants | 602 Participants | 305 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 328 / 410 | 329 / 413 | 50 / 78 | 62 / 82 |
| other Total, other adverse events | 310 / 410 | 349 / 399 | 73 / 77 | 77 / 78 |
| serious Total, serious adverse events | 193 / 410 | 112 / 399 | 32 / 77 | 22 / 78 |
Outcome results
Primary
OS; China Cohort: China Programmed Cell Death Ligand 1 (PD-L1) Negative NSCLC Analysis Set
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 was 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 China cohort DCO date (a maximum of approximately 44 months).
Population: The China PD-L1-negative population analysis set included the subset of participants in the China FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 assay (ie, \<1% PD-L1-membrane expression in tumoral tissue). Only participants randomized in China cohort were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Global: Durvalumab + Tremelimumab | OS; China Cohort: China Programmed Cell Death Ligand 1 (PD-L1) Negative NSCLC Analysis Set | 15.0 months |
| Global: SoC Chemotherapy | OS; China Cohort: China Programmed Cell Death Ligand 1 (PD-L1) Negative NSCLC Analysis Set | 11.7 months |
Comparison: China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.95% CI: [0.322, 1.109]
Primary
Overall Survival (OS); Global Cohort: Blood Tumor Mutational Burden (bTMB) ≥20 Mutations Per Megabase (Mut/Mb) Analysis Set
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 was 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 Global cohort DCO date (a maximum of approximately 44 months).
Population: The bTMB ≥20 mut/Mb analysis set included the subset of participants in the FAS whose blood TMB status was ≥20 mut/Mb at baseline as defined by the GuardantOMNI CDx assay. Only participants randomized in Global cohort were analyzed as bTMB and tissue tumor mutational burden (tTMB) testing was not performed in China cohort.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Global: Durvalumab + Tremelimumab | Overall Survival (OS); Global Cohort: Blood Tumor Mutational Burden (bTMB) ≥20 Mutations Per Megabase (Mut/Mb) Analysis Set | 11.7 months |
| Global: SoC Chemotherapy | Overall Survival (OS); Global Cohort: Blood Tumor Mutational Burden (bTMB) ≥20 Mutations Per Megabase (Mut/Mb) Analysis Set | 9.1 months |
Comparison: Global: Durvalumab + Tremelimumab versus (Vs) Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.p-value: 0.080895% CI: [0.485, 1.045]Log Rank
Secondary
Alive and Progression-Free at 12 Months (APF12); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets
The APF12 was defined as the percentage of participants who were alive and progression free at 12 months from randomization (ie, PFS rate at 12 months). bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.
Time frame: Tumour scans performed at baseline then every 6 weeks up to 12 months.
Population: Participants included in bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb, and bTMB ≥12 mut/Mb analysis sets are reported in this outcome measure. Only participants randomized in Global cohort were analyzed as bTMB and tTMB testing was not performed in China cohort.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Global: Durvalumab + Tremelimumab | Alive and Progression-Free at 12 Months (APF12); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | bTMB ≥20 mut/Mb analysis set | 25.6 percentage of participants |
| Global: Durvalumab + Tremelimumab | Alive and Progression-Free at 12 Months (APF12); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | bTMB ≥16 mut/Mb analysis set | 22.0 percentage of participants |
| Global: Durvalumab + Tremelimumab | Alive and Progression-Free at 12 Months (APF12); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | bTMB ≥12 mut/Mb analysis set | 21.6 percentage of participants |
| Global: SoC Chemotherapy | Alive and Progression-Free at 12 Months (APF12); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | bTMB ≥20 mut/Mb analysis set | 7.0 percentage of participants |
| Global: SoC Chemotherapy | Alive and Progression-Free at 12 Months (APF12); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | bTMB ≥16 mut/Mb analysis set | 12.3 percentage of participants |
| Global: SoC Chemotherapy | Alive and Progression-Free at 12 Months (APF12); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | bTMB ≥12 mut/Mb analysis set | 13.8 percentage of participants |
Secondary
APF12; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets
The APF12 was defined as the percentage of patients who were alive and progression free at 12 months from randomization (ie, PFS rate at 12 months). PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue). Global Cohort: The FAS included all randomized participants prior to the end of global recruitment. China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.
Time frame: Tumour scans performed at baseline then every 6 weeks up to 12 months.
Population: Participants included in PD-L1-negative NSCLC and FAS analysis sets are reported in this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Global: Durvalumab + Tremelimumab | APF12; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | PD-L1-negative NSCLC analysis set | 18.2 percentage of participants |
| Global: Durvalumab + Tremelimumab | APF12; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | FAS | 20.2 percentage of participants |
| Global: SoC Chemotherapy | APF12; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | FAS | 14.9 percentage of participants |
| Global: SoC Chemotherapy | APF12; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | PD-L1-negative NSCLC analysis set | 12.1 percentage of participants |
| China: Durvalumab + Tremelimumab | APF12; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | PD-L1-negative NSCLC analysis set | 15.6 percentage of participants |
| China: Durvalumab + Tremelimumab | APF12; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | FAS | 23.9 percentage of participants |
| China: SoC Chemotherapy | APF12; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | PD-L1-negative NSCLC analysis set | 11.3 percentage of participants |
| China: SoC Chemotherapy | APF12; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | FAS | 16.6 percentage of participants |
Secondary
DoR; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets
DoR (per RECIST 1.1 using Investigator 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 PD (ie, date of PFS event or censoring - date of first response + 1). PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue). Global Cohort: The FAS included all randomized participants prior to the end of global recruitment. China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.
Time frame: Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global or China cohort DCO dates, as applicable (approximately 44 months) for each cohort.
Population: Participants included in PD-L1-negative NSCLC and FAS analysis sets are reported in this outcome measure. Only participants with objective response were included in this analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Global: Durvalumab + Tremelimumab | DoR; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | PD-L1-negative NSCLC analysis set | 10.2 months |
| Global: Durvalumab + Tremelimumab | DoR; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | FAS | 11.1 months |
| Global: SoC Chemotherapy | DoR; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | FAS | 4.9 months |
| Global: SoC Chemotherapy | DoR; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | PD-L1-negative NSCLC analysis set | 4.9 months |
| China: Durvalumab + Tremelimumab | DoR; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | PD-L1-negative NSCLC analysis set | 10.5 months |
| China: Durvalumab + Tremelimumab | DoR; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | FAS | 12.9 months |
| China: SoC Chemotherapy | DoR; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | PD-L1-negative NSCLC analysis set | 6.1 months |
| China: SoC Chemotherapy | DoR; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | FAS | 6.1 months |
Comparison: PD-L1-negative analysis set:~Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer DoR than SoC.95% CI: [0.199, 0.787]
Comparison: PD-L1-negative analysis set:~China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer DoR than SoC.95% CI: [0.183, 2.86]
Comparison: FAS:~Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer DoR than SoC.95% CI: [0.324, 0.588]
Comparison: FAS:~China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer DoR than SoC.95% CI: [0.193, 0.761]
Secondary
Duration of Response (DoR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets
DoR (per RECIST 1.1 using Investigator 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 PD (ie, date of PFS event or censoring - date of first response + 1). bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.
Time frame: Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global cohort DCO date (approximately 44 months).
Population: Participants included in bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb, and bTMB ≥12 mut/Mb analysis sets are reported in this outcome measure. Only participants with objective response and randomized in Global cohort were analyzed as bTMB and tTMB testing was not performed in China cohort.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Global: Durvalumab + Tremelimumab | Duration of Response (DoR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | bTMB ≥20 mut/Mb analysis set | 11.6 months |
| Global: Durvalumab + Tremelimumab | Duration of Response (DoR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | bTMB ≥16 mut/Mb analysis set | 10.6 months |
| Global: Durvalumab + Tremelimumab | Duration of Response (DoR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | bTMB ≥12 mut/Mb analysis set | 11.5 months |
| Global: SoC Chemotherapy | Duration of Response (DoR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | bTMB ≥20 mut/Mb analysis set | 4.2 months |
| Global: SoC Chemotherapy | Duration of Response (DoR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | bTMB ≥16 mut/Mb analysis set | 4.3 months |
| Global: SoC Chemotherapy | Duration of Response (DoR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | bTMB ≥12 mut/Mb analysis set | 4.3 months |
Comparison: bTMB ≥20 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer DoR than SoC.95% CI: [0.113, 0.532]
Comparison: bTMB ≥16 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer DoR than SoC.95% CI: [0.196, 0.639]
Comparison: bTMB ≥12 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer DoR than SoC.95% CI: [0.233, 0.611]
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. ADA prevalence is defined as the percentage of participants with positive ADA result at any time, baseline or post-baseline. Treatment-emergent ADA is defined as the sum of treatment-induced ADA and treatment-boosted ADA. ADA incidence is the percentage of participants who were treatment-emergent ADA-positive. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted to \>=4 fold during the study period. 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 1 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: Global Cohort: The FAS included all randomized participants prior to the end of global recruitment. Any participants recruited in China, after global recruitment had ended, were not included in the FAS.~China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.~The denominator for calculation of percentage for all categories is the number of ADA evaluable participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Global: Durvalumab + Tremelimumab | Number of Participants With ADA Response to Tremelimumab | Treatment-emergent ADA positive (ADA incidence) | 37 Participants |
| Global: Durvalumab + Tremelimumab | Number of Participants With ADA Response to Tremelimumab | Persistent positive | 29 Participants |
| Global: Durvalumab + Tremelimumab | Number of Participants With ADA Response to Tremelimumab | Treatment-induced ADA (positive post-baseline only) | 36 Participants |
| Global: Durvalumab + Tremelimumab | Number of Participants With ADA Response to Tremelimumab | Transient positive | 11 Participants |
| Global: Durvalumab + Tremelimumab | Number of Participants With ADA Response to Tremelimumab | Treatment-boosted ADA | 1 Participants |
| Global: Durvalumab + Tremelimumab | Number of Participants With ADA Response to Tremelimumab | nAb positive at any visit | 33 Participants |
| Global: Durvalumab + Tremelimumab | Number of Participants With ADA Response to Tremelimumab | ADA positive post-baseline and positive at baseline | 4 Participants |
| Global: Durvalumab + Tremelimumab | Number of Participants With ADA Response to Tremelimumab | ADA positive at baseline and not detected post-baseline | 9 Participants |
| Global: Durvalumab + Tremelimumab | Number of Participants With ADA Response to Tremelimumab | ADA positive at any visit (ADA prevalence) | 49 Participants |
| Global: SoC Chemotherapy | Number of Participants With ADA Response to Tremelimumab | ADA positive at baseline and not detected post-baseline | 0 Participants |
| Global: SoC Chemotherapy | Number of Participants With ADA Response to Tremelimumab | ADA positive at any visit (ADA prevalence) | 2 Participants |
| Global: SoC Chemotherapy | Number of Participants With ADA Response to Tremelimumab | Treatment-emergent ADA positive (ADA incidence) | 1 Participants |
| Global: SoC Chemotherapy | Number of Participants With ADA Response to Tremelimumab | Treatment-boosted ADA | 0 Participants |
| Global: SoC Chemotherapy | Number of Participants With ADA Response to Tremelimumab | Treatment-induced ADA (positive post-baseline only) | 1 Participants |
| Global: SoC Chemotherapy | Number of Participants With ADA Response to Tremelimumab | ADA positive post-baseline and positive at baseline | 1 Participants |
| Global: SoC Chemotherapy | Number of Participants With ADA Response to Tremelimumab | Persistent positive | 0 Participants |
| Global: SoC Chemotherapy | Number of Participants With ADA Response to Tremelimumab | Transient positive | 2 Participants |
| Global: SoC Chemotherapy | Number of Participants With ADA Response to Tremelimumab | nAb positive at any visit | 0 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. ADA prevalence is defined as the percentage of participants with positive ADA result at any time, baseline or post-baseline. Treatment-emergent ADA is defined as the sum of treatment-induced ADA and treatment-boosted ADA. ADA incidence is the percentage of participants who were treatment-emergent ADA-positive. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted to \>=4 fold during the study period. 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 1 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: Global Cohort: The FAS included all randomized participants prior to the end of global recruitment. Any participants recruited in China, after global recruitment had ended, were not included in the FAS.~China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.~The denominator for calculation of percentage for all categories is the number of ADA evaluable participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Global: Durvalumab + Tremelimumab | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | ADA positive post-baseline and positive at baseline | 1 Participants |
| Global: Durvalumab + Tremelimumab | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | Treatment-boosted ADA | 0 Participants |
| Global: Durvalumab + Tremelimumab | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | Persistent positive | 11 Participants |
| Global: Durvalumab + Tremelimumab | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | Treatment-emergent ADA positive (ADA incidence) | 12 Participants |
| Global: Durvalumab + Tremelimumab | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | Transient positive | 2 Participants |
| Global: Durvalumab + Tremelimumab | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | nAb positive at any visit | 3 Participants |
| Global: Durvalumab + Tremelimumab | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | Treatment-induced ADA (positive post-baseline only) | 12 Participants |
| Global: Durvalumab + Tremelimumab | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | ADA positive at baseline and not detected post-baseline | 13 Participants |
| Global: Durvalumab + Tremelimumab | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | ADA positive at any visit (ADA prevalence) | 26 Participants |
| Global: SoC Chemotherapy | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | ADA positive at baseline and not detected post-baseline | 0 Participants |
| Global: SoC Chemotherapy | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | ADA positive at any visit (ADA prevalence) | 1 Participants |
| Global: SoC Chemotherapy | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | Treatment-emergent ADA positive (ADA incidence) | 1 Participants |
| Global: SoC Chemotherapy | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | Treatment-boosted ADA | 0 Participants |
| Global: SoC Chemotherapy | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | Treatment-induced ADA (positive post-baseline only) | 1 Participants |
| Global: SoC Chemotherapy | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | ADA positive post-baseline and positive at baseline | 0 Participants |
| Global: SoC Chemotherapy | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | Persistent positive | 1 Participants |
| Global: SoC Chemotherapy | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | nAb positive at any visit | 0 Participants |
| Global: SoC Chemotherapy | Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab | Transient positive | 0 Participants |
Secondary
Objective Response Rate (ORR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets
The ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with at least 1 visit response of complete response (CR) or partial response (PR) prior to PD. bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay. tTMB ≥14 mut/Mb, tTMB ≥12 mut/Mb, tTMB ≥10 mut/Mb and tTMB ≥8 mut/Mb analysis sets included the subset of participants in FAS whose tTMB status was ≥14 mut/Mb, ≥12 mut/Mb, ≥10 mut/Mb and ≥8 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.
Time frame: Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global cohort DCO date (approximately 44 months).
Population: Participants included in bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb, bTMB ≥12 mut/Mb, tTMB ≥14 mut/Mb, tTMB ≥12 mut/Mb, tTMB ≥10 mut/Mb, and tTMB ≥8 mut/Mb analysis sets with measurable disease are reported in this outcome measure. Only participants randomized in Global cohort were analyzed as bTMB and tTMB testing was not performed in China cohort.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Global: Durvalumab + Tremelimumab | Objective Response Rate (ORR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | bTMB ≥12 mut/Mb analysis set | 28.7 percentage of participants |
| Global: Durvalumab + Tremelimumab | Objective Response Rate (ORR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | tTMB ≥12 mut/Mb analysis set | 42.6 percentage of participants |
| Global: Durvalumab + Tremelimumab | Objective Response Rate (ORR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | bTMB ≥16 mut/Mb analysis set | 31.2 percentage of participants |
| Global: Durvalumab + Tremelimumab | Objective Response Rate (ORR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | tTMB ≥10 mut/Mb analysis set | 37.7 percentage of participants |
| Global: Durvalumab + Tremelimumab | Objective Response Rate (ORR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | tTMB ≥14 mut/Mb analysis set | 61.3 percentage of participants |
| Global: Durvalumab + Tremelimumab | Objective Response Rate (ORR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | tTMB ≥8 mut/Mb analysis set | 36.7 percentage of participants |
| Global: Durvalumab + Tremelimumab | Objective Response Rate (ORR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | bTMB ≥20 mut/Mb analysis set | 27.5 percentage of participants |
| Global: SoC Chemotherapy | Objective Response Rate (ORR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | tTMB ≥8 mut/Mb analysis set | 41.2 percentage of participants |
| Global: SoC Chemotherapy | Objective Response Rate (ORR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | bTMB ≥20 mut/Mb analysis set | 43.3 percentage of participants |
| Global: SoC Chemotherapy | Objective Response Rate (ORR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | bTMB ≥16 mut/Mb analysis set | 46.1 percentage of participants |
| Global: SoC Chemotherapy | Objective Response Rate (ORR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | bTMB ≥12 mut/Mb analysis set | 42.0 percentage of participants |
| Global: SoC Chemotherapy | Objective Response Rate (ORR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | tTMB ≥14 mut/Mb analysis set | 44.7 percentage of participants |
| Global: SoC Chemotherapy | Objective Response Rate (ORR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | tTMB ≥12 mut/Mb analysis set | 41.8 percentage of participants |
| Global: SoC Chemotherapy | Objective Response Rate (ORR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | tTMB ≥10 mut/Mb analysis set | 42.5 percentage of participants |
Comparison: bTMB ≥20 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.95% CI: [0.236, 1.03]
Comparison: bTMB ≥16 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.95% CI: [0.288, 0.968]
Comparison: bTMB ≥12 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.95% CI: [0.336, 0.908]
Comparison: tTMB ≥14 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.95% CI: [0.752, 5.234]
Comparison: tTMB ≥12 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.95% CI: [0.482, 2.214]
Comparison: tTMB ≥10 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.95% CI: [0.43, 1.548]
Comparison: tTMB ≥8 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.95% CI: [0.456, 1.486]
Secondary
ORR; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets
The ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with at least 1 visit response of CR or PR prior to PD. PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue). Global Cohort: The FAS included all randomized participants prior to the end of global recruitment. China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses. PD-L1 TC ≥25% and PD-L1 TC ≥50% analysis sets included the subset of participants in the FAS whose PD-L1 status was TC ≥25% and TC ≥50% membrane expression in tumoral tissue, respectively at baseline as defined by the Ventana SP263 PD-L1 Assay.
Time frame: Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global or China cohort DCO dates, as applicable (approximately 44 months) for each cohort.
Population: Participants included in PD-L1-negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% analysis sets with measurable disease are reported in this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Global: Durvalumab + Tremelimumab | ORR; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | FAS | 25.9 percentage of participants |
| Global: Durvalumab + Tremelimumab | ORR; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1 TC ≥25% analysis set | 35.2 percentage of participants |
| Global: Durvalumab + Tremelimumab | ORR; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1 TC ≥50% analysis set | 37.4 percentage of participants |
| Global: Durvalumab + Tremelimumab | ORR; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1-negative NSCLC analysis set | 23.1 percentage of participants |
| Global: SoC Chemotherapy | ORR; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1-negative NSCLC analysis set | 38.8 percentage of participants |
| Global: SoC Chemotherapy | ORR; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1 TC ≥50% analysis set | 44.0 percentage of participants |
| Global: SoC Chemotherapy | ORR; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1 TC ≥25% analysis set | 43.9 percentage of participants |
| Global: SoC Chemotherapy | ORR; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | FAS | 41.7 percentage of participants |
| China: Durvalumab + Tremelimumab | ORR; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1 TC ≥50% analysis set | 60.0 percentage of participants |
| China: Durvalumab + Tremelimumab | ORR; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1-negative NSCLC analysis set | 23.1 percentage of participants |
| China: Durvalumab + Tremelimumab | ORR; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1 TC ≥25% analysis set | 54.8 percentage of participants |
| China: Durvalumab + Tremelimumab | ORR; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | FAS | 35.9 percentage of participants |
| China: SoC Chemotherapy | ORR; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1 TC ≥25% analysis set | 40.6 percentage of participants |
| China: SoC Chemotherapy | ORR; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | FAS | 39.0 percentage of participants |
| China: SoC Chemotherapy | ORR; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1-negative NSCLC analysis set | 41.4 percentage of participants |
| China: SoC Chemotherapy | ORR; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1 TC ≥50% analysis set | 46.4 percentage of participants |
Comparison: PD-L1-negative analysis set:~Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.95% CI: [0.245, 0.869]
Comparison: PD-L1-negative analysis set:~China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy~An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.95% CI: [0.124, 1.337]Binomial exact test
Comparison: FAS:~Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.95% CI: [0.356, 0.647]
Comparison: FAS:~China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy~An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.95% CI: [0.45, 1.66]
Comparison: PD-L1 TC ≥25% analysis set:~Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.95% CI: [0.443, 1.079]
Comparison: PD-L1 TC ≥ 25% analysis set:~China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy~An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.95% CI: [0.658, 4.919]
Comparison: PD-L1 TC ≥50% analysis set:~Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.95% CI: [0.449, 1.291]
Comparison: PD-L1 TC ≥50% analysis set:~China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy~An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.95% CI: [0.585, 5.27]
Secondary
OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets
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). PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue). Global Cohort: The FAS included all randomized participants prior to the end of global recruitment. China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.
Time frame: Months 12, 18 and 24
Population: Participants included in PD-L1-negative NSCLC and FAS analysis sets are reported in this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Global: Durvalumab + Tremelimumab | OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Month 12: PD-L1-negative NSCLC analysis set | 47.8 percentage of participants |
| Global: Durvalumab + Tremelimumab | OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Month 12: FAS | 47.7 percentage of participants |
| Global: Durvalumab + Tremelimumab | OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Month 18: PD-L1-negative NSCLC analysis set | 34.1 percentage of participants |
| Global: Durvalumab + Tremelimumab | OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Month 18: FAS | 34.8 percentage of participants |
| Global: Durvalumab + Tremelimumab | OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Month 24: PD-L1-negative NSCLC analysis set | 22.1 percentage of participants |
| Global: Durvalumab + Tremelimumab | OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Month 24: FAS | 25.7 percentage of participants |
| Global: SoC Chemotherapy | OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Month 24: FAS | 23.4 percentage of participants |
| Global: SoC Chemotherapy | OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Month 18: FAS | 34.6 percentage of participants |
| Global: SoC Chemotherapy | OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Month 12: PD-L1-negative NSCLC analysis set | 52.8 percentage of participants |
| Global: SoC Chemotherapy | OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Month 18: PD-L1-negative NSCLC analysis set | 34.5 percentage of participants |
| Global: SoC Chemotherapy | OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Month 12: FAS | 50.0 percentage of participants |
| Global: SoC Chemotherapy | OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Month 24: PD-L1-negative NSCLC analysis set | 22.3 percentage of participants |
| China: Durvalumab + Tremelimumab | OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Month 12: FAS | 72.8 percentage of participants |
| China: Durvalumab + Tremelimumab | OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Month 18: PD-L1-negative NSCLC analysis set | 44.0 percentage of participants |
| China: Durvalumab + Tremelimumab | OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Month 18: FAS | 54.6 percentage of participants |
| China: Durvalumab + Tremelimumab | OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Month 24: FAS | 44.2 percentage of participants |
| China: Durvalumab + Tremelimumab | OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Month 24: PD-L1-negative NSCLC analysis set | 36.0 percentage of participants |
| China: Durvalumab + Tremelimumab | OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Month 12: PD-L1-negative NSCLC analysis set | 68.0 percentage of participants |
| China: SoC Chemotherapy | OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Month 24: PD-L1-negative NSCLC analysis set | 17.9 percentage of participants |
| China: SoC Chemotherapy | OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Month 24: FAS | 30.4 percentage of participants |
| China: SoC Chemotherapy | OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Month 12: FAS | 53.1 percentage of participants |
| China: SoC Chemotherapy | OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Month 18: FAS | 41.8 percentage of participants |
| China: SoC Chemotherapy | OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Month 12: PD-L1-negative NSCLC analysis set | 46.4 percentage of participants |
| China: SoC Chemotherapy | OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | Month 18: PD-L1-negative NSCLC analysis set | 39.3 percentage of participants |
Secondary
OS at Months 12, 18 and 24; Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets
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). bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.
Time frame: Months 12, 18 and 24
Population: Participants included in bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb, and bTMB ≥12 mut/Mb analysis sets are reported in this outcome measure. Only participants randomized in Global cohort were analyzed as bTMB and tTMB testing was not performed in China cohort.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Global: Durvalumab + Tremelimumab | OS at Months 12, 18 and 24; Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | Month 12: bTMB ≥16 mut/Mb analysis set | 50.5 percentage of participants |
| Global: Durvalumab + Tremelimumab | OS at Months 12, 18 and 24; Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | Month 18: bTMB ≥12 mut/Mb analysis set | 29.4 percentage of participants |
| Global: Durvalumab + Tremelimumab | OS at Months 12, 18 and 24; Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | Month 18: bTMB ≥20 mut/Mb analysis set | 36.2 percentage of participants |
| Global: Durvalumab + Tremelimumab | OS at Months 12, 18 and 24; Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | Month 24: bTMB ≥20 mut/Mb analysis set | 26.1 percentage of participants |
| Global: Durvalumab + Tremelimumab | OS at Months 12, 18 and 24; Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | Month 12: bTMB ≥12 mut/Mb analysis set | 46.9 percentage of participants |
| Global: Durvalumab + Tremelimumab | OS at Months 12, 18 and 24; Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | Month 24: bTMB ≥16 mut/Mb analysis set | 24.0 percentage of participants |
| Global: Durvalumab + Tremelimumab | OS at Months 12, 18 and 24; Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | Month 18: bTMB ≥16 mut/Mb analysis set | 35.5 percentage of participants |
| Global: Durvalumab + Tremelimumab | OS at Months 12, 18 and 24; Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | Month 24: bTMB ≥12 mut/Mb analysis set | 21.3 percentage of participants |
| Global: Durvalumab + Tremelimumab | OS at Months 12, 18 and 24; Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | Month 12: bTMB ≥20 mut/Mb analysis set | 49.3 percentage of participants |
| Global: SoC Chemotherapy | OS at Months 12, 18 and 24; Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | Month 24: bTMB ≥12 mut/Mb analysis set | 19.0 percentage of participants |
| Global: SoC Chemotherapy | OS at Months 12, 18 and 24; Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | Month 12: bTMB ≥20 mut/Mb analysis set | 40.8 percentage of participants |
| Global: SoC Chemotherapy | OS at Months 12, 18 and 24; Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | Month 12: bTMB ≥16 mut/Mb analysis set | 48.9 percentage of participants |
| Global: SoC Chemotherapy | OS at Months 12, 18 and 24; Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | Month 12: bTMB ≥12 mut/Mb analysis set | 44.6 percentage of participants |
| Global: SoC Chemotherapy | OS at Months 12, 18 and 24; Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | Month 18: bTMB ≥20 mut/Mb analysis set | 20.4 percentage of participants |
| Global: SoC Chemotherapy | OS at Months 12, 18 and 24; Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | Month 18: bTMB ≥16 mut/Mb analysis set | 28.5 percentage of participants |
| Global: SoC Chemotherapy | OS at Months 12, 18 and 24; Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | Month 18: bTMB ≥12 mut/Mb analysis set | 27.8 percentage of participants |
| Global: SoC Chemotherapy | OS at Months 12, 18 and 24; Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | Month 24: bTMB ≥20 mut/Mb analysis set | 13.6 percentage of participants |
| Global: SoC Chemotherapy | OS at Months 12, 18 and 24; Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | Month 24: bTMB ≥16 mut/Mb analysis set | 18.2 percentage of participants |
Secondary
OS; Global and China Cohorts: FAS, PD-L1 Tumor Cell (TC) ≥25%, and PD-L1 TC ≥50% Analysis Sets
The OS was defined as time from 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 was censored based on last recorded date on which participant was known to be alive. Global Cohort: The FAS included all randomized participants prior to the end of global recruitment. Any participants recruited in China, after global recruitment had ended, were not included in the FAS. China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses. PD-L1 TC ≥25% and PD-L1 TC ≥50% analysis sets included the subset of participants in the FAS whose PD-L1 status was TC ≥25% and TC ≥50% membrane expression in tumoral tissue, respectively at baseline as defined by the Ventana SP263 PD-L1 Assay.
Time frame: From baseline (Day 1, Week 0) until death due to any cause, assessed up to the Global or China cohort DCO dates, as applicable (a maximum of approximately 44 months) for each cohort.
Population: Participants included in FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% analysis sets are reported in this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Global: Durvalumab + Tremelimumab | OS; Global and China Cohorts: FAS, PD-L1 Tumor Cell (TC) ≥25%, and PD-L1 TC ≥50% Analysis Sets | FAS | 10.9 months |
| Global: Durvalumab + Tremelimumab | OS; Global and China Cohorts: FAS, PD-L1 Tumor Cell (TC) ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1 TC ≥50% analysis set | 14.1 months |
| Global: Durvalumab + Tremelimumab | OS; Global and China Cohorts: FAS, PD-L1 Tumor Cell (TC) ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1 TC ≥25% analysis set | 12.2 months |
| Global: SoC Chemotherapy | OS; Global and China Cohorts: FAS, PD-L1 Tumor Cell (TC) ≥25%, and PD-L1 TC ≥50% Analysis Sets | FAS | 12.1 months |
| Global: SoC Chemotherapy | OS; Global and China Cohorts: FAS, PD-L1 Tumor Cell (TC) ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1 TC ≥50% analysis set | 10.5 months |
| Global: SoC Chemotherapy | OS; Global and China Cohorts: FAS, PD-L1 Tumor Cell (TC) ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1 TC ≥25% analysis set | 10.4 months |
| China: Durvalumab + Tremelimumab | OS; Global and China Cohorts: FAS, PD-L1 Tumor Cell (TC) ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1 TC ≥25% analysis set | 36.6 months |
| China: Durvalumab + Tremelimumab | OS; Global and China Cohorts: FAS, PD-L1 Tumor Cell (TC) ≥25%, and PD-L1 TC ≥50% Analysis Sets | FAS | 20.0 months |
| China: Durvalumab + Tremelimumab | OS; Global and China Cohorts: FAS, PD-L1 Tumor Cell (TC) ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1 TC ≥50% analysis set | 36.6 months |
| China: SoC Chemotherapy | OS; Global and China Cohorts: FAS, PD-L1 Tumor Cell (TC) ≥25%, and PD-L1 TC ≥50% Analysis Sets | FAS | 14.1 months |
| China: SoC Chemotherapy | OS; Global and China Cohorts: FAS, PD-L1 Tumor Cell (TC) ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1 TC ≥50% analysis set | 15.8 months |
| China: SoC Chemotherapy | OS; Global and China Cohorts: FAS, PD-L1 Tumor Cell (TC) ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1 TC ≥25% analysis set | 15.8 months |
Comparison: FAS:~Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.95% CI: [0.871, 1.186]
Comparison: FAS:~China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.95% CI: [0.48, 1.018]
Comparison: PD-L1 TC ≥25% analysis set:~Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.95% CI: [0.654, 1.078]
Comparison: PD-L1 TC ≥ 25% analysis set:~China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.95% CI: [0.289, 1.065]
Comparison: PD-L1 TC ≥50% analysis set:~Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.95% CI: [0.587, 1.081]
Comparison: PD-L1 TC ≥50% analysis set:~China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.95% CI: [0.222, 0.955]
Secondary
OS; Global Cohort: bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets
OS was defined as time from 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 time of analysis was censored based on last recorded date on which participant was known to be alive. bTMB ≥16 mut/Mb, bTMB ≥12 mut/Mb and bTMB \<20 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥16 mut/Mb, ≥12 mut/Mb and \<20 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay. PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue). bTMB non-evaluable analysis set included the subset of participants in FAS whose bTMB status at baseline could not be determined by the GuardantOMNI CDx assay or whose sample was not available. tTMB analysis sets are defined same as the bTMB analysis sets.
Time frame: From baseline (Day 1, Week 0) until death due to any cause, assessed up to the Global cohort DCO date (a maximum of approximately 44 months).
Population: Participants included in bTMB ≥16 mut/Mb, bTMB ≥12 mut/Mb, PD-L1-Negative NSCLC, bTMB \<20 mut/Mb, bTMB non-evaluable population, tTMB ≥14 mut/Mb, tTMB ≥12 mut/Mb, tTMB ≥10 mut/Mb, and tTMB ≥8 mut/Mb analysis sets are reported in this outcome measure. Only participants randomized in Global cohort were analyzed as bTMB and tTMB testing was not performed in China cohort.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Global: Durvalumab + Tremelimumab | OS; Global Cohort: bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | bTMB ≥12 mut/Mb analysis set | 10.9 months |
| Global: Durvalumab + Tremelimumab | OS; Global Cohort: bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | tTMB ≥14 mut/Mb analysis set | 17.5 months |
| Global: Durvalumab + Tremelimumab | OS; Global Cohort: bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | bTMB <20 mut/Mb analysis set | 9.9 months |
| Global: Durvalumab + Tremelimumab | OS; Global Cohort: bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | tTMB ≥12 mut/Mb analysis set | 11.1 months |
| Global: Durvalumab + Tremelimumab | OS; Global Cohort: bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | PD-L1 negative analysis set | 11.1 months |
| Global: Durvalumab + Tremelimumab | OS; Global Cohort: bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | tTMB ≥10 mut/Mb analysis set | 11.1 months |
| Global: Durvalumab + Tremelimumab | OS; Global Cohort: bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | bTMB non-evaluable analysis set | 9.3 months |
| Global: Durvalumab + Tremelimumab | OS; Global Cohort: bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | tTMB ≥8 mut/Mb analysis set | 11.0 months |
| Global: Durvalumab + Tremelimumab | OS; Global Cohort: bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | bTMB ≥16 mut/Mb analysis set | 12.1 months |
| Global: SoC Chemotherapy | OS; Global Cohort: bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | tTMB ≥8 mut/Mb analysis set | 10.2 months |
| Global: SoC Chemotherapy | OS; Global Cohort: bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | bTMB ≥16 mut/Mb analysis set | 11.9 months |
| Global: SoC Chemotherapy | OS; Global Cohort: bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | bTMB ≥12 mut/Mb analysis set | 10.3 months |
| Global: SoC Chemotherapy | OS; Global Cohort: bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | PD-L1 negative analysis set | 12.5 months |
| Global: SoC Chemotherapy | OS; Global Cohort: bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | bTMB <20 mut/Mb analysis set | 11.5 months |
| Global: SoC Chemotherapy | OS; Global Cohort: bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | bTMB non-evaluable analysis set | 10.4 months |
| Global: SoC Chemotherapy | OS; Global Cohort: bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | tTMB ≥14 mut/Mb analysis set | 10.6 months |
| Global: SoC Chemotherapy | OS; Global Cohort: bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | tTMB ≥12 mut/Mb analysis set | 13.9 months |
| Global: SoC Chemotherapy | OS; Global Cohort: bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | tTMB ≥10 mut/Mb analysis set | 10.6 months |
Comparison: bTMB ≥16 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.95% CI: [0.629, 1.201]
Comparison: bTMB ≥12 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.95% CI: [0.726, 1.213]
Comparison: PD-L1 negative analysis set:~Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.95% CI: [0.786, 1.464]
Comparison: bTMB \<20 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.95% CI: [0.835, 1.302]
Comparison: bTMB non-evaluable analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.95% CI: [0.758, 1.353]
Comparison: tTMB ≥14 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.95% CI: [0.309, 1.008]
Comparison: tTMB ≥12 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.95% CI: [0.56, 1.35]
Comparison: tTMB ≥10 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.95% CI: [0.614, 1.251]
Comparison: tTMB ≥8 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.95% CI: [0.564, 1.08]
Secondary
PFS2; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets
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, or death (ie, date of PFS2 event or censoring - date of randomization + 1). PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue). Global Cohort: The FAS included all randomized participants prior to the end of global recruitment. China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.
Time frame: Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global or China cohort DCO dates, as applicable (approximately 44 months) for each cohort.
Population: Participants included in PD-L1-negative NSCLC and FAS analysis sets are reported in this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Global: Durvalumab + Tremelimumab | PFS2; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | PD-L1-negative NSCLC analysis set | 9.1 months |
| Global: Durvalumab + Tremelimumab | PFS2; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | FAS | 9.4 months |
| Global: SoC Chemotherapy | PFS2; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | FAS | 10.4 months |
| Global: SoC Chemotherapy | PFS2; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | PD-L1-negative NSCLC analysis set | 12.4 months |
| China: Durvalumab + Tremelimumab | PFS2; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | PD-L1-negative NSCLC analysis set | 13.8 months |
| China: Durvalumab + Tremelimumab | PFS2; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | FAS | 15.5 months |
| China: SoC Chemotherapy | PFS2; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | PD-L1-negative NSCLC analysis set | 10.3 months |
| China: SoC Chemotherapy | PFS2; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets | FAS | 12.9 months |
Comparison: FAS:~Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab to be associated with a longer time to second progression than SoC.95% CI: [0.845, 1.147]
Comparison: FAS:~China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab to be associated with a longer time to second progression than SoC.95% CI: [0.492, 1.03]
Comparison: PD-L1-negative analysis set:~Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab to be associated with a longer time to second progression than SoC.95% CI: [0.748, 1.388]
Comparison: PD-L1-negative analysis set:~China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab to be associated with a longer time to second progression than SoC.95% CI: [0.36, 1.219]
Secondary
PFS; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets
PFS (per RECIST 1.1 using Investigator assessments) was defined as time from date of randomization until date of objective PD or death regardless of whether participant withdrew from randomized therapy or received another anticancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). PD-L1-negative analysis set included subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue). Global Cohort: FAS included all randomized participants prior to end of global recruitment. China Cohort: China FAS included all randomized participants in China cohort and were used for all China only efficacy analyses. PD-L1 TC ≥25% and PD-L1 TC ≥50% analysis sets included subset of participants in FAS whose PD-L1 status was TC ≥25% and TC ≥50% membrane expression in tumoral tissue, respectively at baseline as defined by the Ventana SP263 PD-L1 Assay.
Time frame: Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global or China cohort DCO dates, as applicable (approximately 44 months) for each cohort.
Population: Participants included in PD-L1-negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% analysis sets are reported in this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Global: Durvalumab + Tremelimumab | PFS; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1-negative NSCLC analysis set | 4.1 months |
| Global: Durvalumab + Tremelimumab | PFS; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | FAS | 4.0 months |
| Global: Durvalumab + Tremelimumab | PFS; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1 TC ≥25% analysis set | 4.2 months |
| Global: Durvalumab + Tremelimumab | PFS; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1 TC ≥50% analysis set | 4.6 months |
| Global: SoC Chemotherapy | PFS; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | FAS | 5.6 months |
| Global: SoC Chemotherapy | PFS; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1 TC ≥25% analysis set | 5.4 months |
| Global: SoC Chemotherapy | PFS; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1 TC ≥50% analysis set | 5.4 months |
| Global: SoC Chemotherapy | PFS; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1-negative NSCLC analysis set | 5.6 months |
| China: Durvalumab + Tremelimumab | PFS; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1 TC ≥25% analysis set | 6.8 months |
| China: Durvalumab + Tremelimumab | PFS; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | FAS | 4.2 months |
| China: Durvalumab + Tremelimumab | PFS; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1 TC ≥50% analysis set | 6.8 months |
| China: Durvalumab + Tremelimumab | PFS; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1-negative NSCLC analysis set | 5.1 months |
| China: SoC Chemotherapy | PFS; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1 TC ≥50% analysis set | 5.7 months |
| China: SoC Chemotherapy | PFS; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | FAS | 6.0 months |
| China: SoC Chemotherapy | PFS; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1-negative NSCLC analysis set | 6.0 months |
| China: SoC Chemotherapy | PFS; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets | PD-L1 TC ≥25% analysis set | 5.7 months |
Comparison: PD-L1-negative analysis set:~Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.95% CI: [0.81, 1.517]
Comparison: PD-L1-negative analysis set:~China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.95% CI: [0.592, 2.141]
Comparison: FAS:~Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.95% CI: [0.924, 1.253]
Comparison: FAS:~China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.95% CI: [0.655, 1.362]
Comparison: PD-L1 TC ≥25% analysis set:~Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.95% CI: [0.621, 1.024]
Comparison: PD-L1 TC ≥ 25% analysis set:~China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.95% CI: [0.389, 1.317]
Comparison: PD-L1 TC ≥50% analysis set:~Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.95% CI: [0.542, 1.01]
Comparison: PD-L1 TC ≥50% analysis set:~China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.95% CI: [0.335, 1.251]
Secondary
Progression-Free Survival (PFS); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets
The PFS (per Response Evaluation Criteria in Solid Tumors, version 1.1 \[RECIST 1.1\] using Investigator assessments) was defined as the time from the date of randomization until the date of objective PD or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay. tTMB ≥14 mut/Mb, tTMB ≥12 mut/Mb, tTMB ≥10 mut/Mb and tTMB ≥8 mut/Mb analysis sets included the subset of participants in FAS whose tTMB status was ≥14 mut/Mb, ≥12 mut/Mb, ≥10 mut/Mb and ≥8 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.
Time frame: Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global cohort DCO date (approximately 44 months).
Population: Participants included in bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb, bTMB ≥12 mut/Mb, tTMB ≥14 mut/Mb, tTMB ≥12 mut/Mb, tTMB ≥10 mut/Mb, and tTMB ≥8 mut/Mb analysis sets are reported in this outcome measure. Only participants randomized in Global cohort were analyzed as bTMB and tTMB testing was not performed in China cohort.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Global: Durvalumab + Tremelimumab | Progression-Free Survival (PFS); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | bTMB ≥12 mut/Mb analysis set | 3.9 months |
| Global: Durvalumab + Tremelimumab | Progression-Free Survival (PFS); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | tTMB ≥12 mut/Mb analysis set | 5.2 months |
| Global: Durvalumab + Tremelimumab | Progression-Free Survival (PFS); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | bTMB ≥16 mut/Mb analysis set | 4.2 months |
| Global: Durvalumab + Tremelimumab | Progression-Free Survival (PFS); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | tTMB ≥10 mut/Mb analysis set | 4.3 months |
| Global: Durvalumab + Tremelimumab | Progression-Free Survival (PFS); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | tTMB ≥14 mut/Mb analysis set | 8.7 months |
| Global: Durvalumab + Tremelimumab | Progression-Free Survival (PFS); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | tTMB ≥8 mut/Mb analysis set | 4.4 months |
| Global: Durvalumab + Tremelimumab | Progression-Free Survival (PFS); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | bTMB ≥20 mut/Mb analysis set | 4.2 months |
| Global: SoC Chemotherapy | Progression-Free Survival (PFS); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | tTMB ≥8 mut/Mb analysis set | 5.0 months |
| Global: SoC Chemotherapy | Progression-Free Survival (PFS); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | bTMB ≥20 mut/Mb analysis set | 5.1 months |
| Global: SoC Chemotherapy | Progression-Free Survival (PFS); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | bTMB ≥16 mut/Mb analysis set | 5.5 months |
| Global: SoC Chemotherapy | Progression-Free Survival (PFS); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | bTMB ≥12 mut/Mb analysis set | 5.1 months |
| Global: SoC Chemotherapy | Progression-Free Survival (PFS); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | tTMB ≥14 mut/Mb analysis set | 5.8 months |
| Global: SoC Chemotherapy | Progression-Free Survival (PFS); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | tTMB ≥12 mut/Mb analysis set | 5.8 months |
| Global: SoC Chemotherapy | Progression-Free Survival (PFS); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets | tTMB ≥10 mut/Mb analysis set | 5.1 months |
Comparison: bTMB ≥20 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.95% CI: [0.514, 1.146]
Comparison: bTMB ≥16 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.95% CI: [0.623, 1.189]
Comparison: bTMB ≥12 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.95% CI: [0.714, 1.193]
Comparison: tTMB ≥14 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.95% CI: [0.258, 0.818]
Comparison: tTMB ≥12 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.95% CI: [0.524, 1.228]
Comparison: tTMB ≥10 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.95% CI: [0.585, 1.177]
Comparison: tTMB ≥8 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.95% CI: [0.534, 1.017]
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 and 12; pre-dose on Week 24 and at follow-up Month 3
Population: Global Cohort: The FAS included all randomized participants prior to the end of global recruitment. Any participants recruited in China, after global recruitment had ended, were not included in the FAS.~China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Global: Durvalumab + Tremelimumab | Serum Concentrations of Durvalumab | Week 0: Pre-infusion | NA microgram per milliliter (µg/mL) | — |
| Global: Durvalumab + Tremelimumab | Serum Concentrations of Durvalumab | Week 0: End of infusion | 418.6 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 74.8 |
| Global: Durvalumab + Tremelimumab | Serum Concentrations of Durvalumab | Week 12: Pre-infusion | 77.5 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 138.1 |
| Global: Durvalumab + Tremelimumab | Serum Concentrations of Durvalumab | Week 12: End of infusion | 434.3 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 105.6 |
| Global: Durvalumab + Tremelimumab | Serum Concentrations of Durvalumab | Week 24: Pre-infusion | 108.8 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 95.7 |
| Global: Durvalumab + Tremelimumab | Serum Concentrations of Durvalumab | Follow-up Month 3 | 8.8 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 253.9 |
| Global: SoC Chemotherapy | Serum Concentrations of Durvalumab | Week 24: Pre-infusion | 85.6 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 93.9 |
| Global: SoC Chemotherapy | Serum Concentrations of Durvalumab | Week 0: Pre-infusion | NA microgram per milliliter (µg/mL) | — |
| Global: SoC Chemotherapy | Serum Concentrations of Durvalumab | Week 12: End of infusion | 448.9 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 40 |
| Global: SoC Chemotherapy | Serum Concentrations of Durvalumab | Week 0: End of infusion | 392.7 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 48.9 |
| Global: SoC Chemotherapy | Serum Concentrations of Durvalumab | Follow-up Month 3 | 5.4 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 351.7 |
| Global: SoC Chemotherapy | Serum Concentrations of Durvalumab | Week 12: Pre-infusion | 72.4 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 55 |
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: Global Cohort: The FAS included all randomized participants prior to the end of global recruitment. Any participants recruited in China, after global recruitment had ended, were not included in the FAS.~China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Global: Durvalumab + Tremelimumab | Serum Concentrations of Tremelimumab | Week 0: End of infusion | 20.3 µg/mL | Geometric Coefficient of Variation 38.7 |
| Global: Durvalumab + Tremelimumab | Serum Concentrations of Tremelimumab | Week 12: End of infusion | 20.8 µg/mL | Geometric Coefficient of Variation 67.4 |
| Global: Durvalumab + Tremelimumab | Serum Concentrations of Tremelimumab | Week 12: Pre-infusion | 3.4 µg/mL | Geometric Coefficient of Variation 99.6 |
| Global: Durvalumab + Tremelimumab | Serum Concentrations of Tremelimumab | Follow-up Month 3 | NA µg/mL | — |
| Global: Durvalumab + Tremelimumab | Serum Concentrations of Tremelimumab | Week 0: Pre-infusion | NA µg/mL | — |
| Global: SoC Chemotherapy | Serum Concentrations of Tremelimumab | Follow-up Month 3 | NA µg/mL | — |
| Global: SoC Chemotherapy | Serum Concentrations of Tremelimumab | Week 0: Pre-infusion | NA µg/mL | — |
| Global: SoC Chemotherapy | Serum Concentrations of Tremelimumab | Week 0: End of infusion | 18.4 µg/mL | Geometric Coefficient of Variation 43.3 |
| Global: SoC Chemotherapy | Serum Concentrations of Tremelimumab | Week 12: Pre-infusion | 3.3 µg/mL | Geometric Coefficient of Variation 64.6 |
| Global: SoC Chemotherapy | Serum Concentrations of Tremelimumab | Week 12: End of infusion | 23.2 µg/mL | Geometric Coefficient of Variation 43.4 |
Secondary
Time From Randomization to Second Progression or Death (PFS2); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets
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, or death (ie, date of PFS2 event or censoring - date of randomization + 1). bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.
Time frame: Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global cohort DCO date (approximately 44 months).
Population: Participants included in bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb, and bTMB ≥12 mut/Mb analysis sets are reported in this outcome measure. Only participants randomized in Global cohort were analyzed as bTMB and tTMB testing was not performed in China cohort.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Global: Durvalumab + Tremelimumab | Time From Randomization to Second Progression or Death (PFS2); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | bTMB ≥20 mut/Mb analysis set | 10.6 months |
| Global: Durvalumab + Tremelimumab | Time From Randomization to Second Progression or Death (PFS2); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | bTMB ≥16 mut/Mb analysis set | 10.9 months |
| Global: Durvalumab + Tremelimumab | Time From Randomization to Second Progression or Death (PFS2); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | bTMB ≥12 mut/Mb analysis set | 9.9 months |
| Global: SoC Chemotherapy | Time From Randomization to Second Progression or Death (PFS2); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | bTMB ≥20 mut/Mb analysis set | 8.6 months |
| Global: SoC Chemotherapy | Time From Randomization to Second Progression or Death (PFS2); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | bTMB ≥16 mut/Mb analysis set | 10.5 months |
| Global: SoC Chemotherapy | Time From Randomization to Second Progression or Death (PFS2); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets | bTMB ≥12 mut/Mb analysis set | 9.0 months |
Comparison: bTMB ≥20 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab to be associated with a longer time to second progression than SoC.95% CI: [0.494, 1.058]
Comparison: bTMB ≥16 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab to be associated with a longer time to second progression than SoC.95% CI: [0.607, 1.151]
Comparison: bTMB ≥12 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy~A HR \<1 favors Durvalumab + Tremelimumab to be associated with a longer time to second progression than SoC.95% CI: [0.689, 1.146]