OS; T + D + SoC Compared With SoC Alone and T + D + SoC Compared With D + SoC

T + D + SoC

During chemotherapy (combination) stage: Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg (in combination with durvalumab) at Week 16 post-chemotherapy. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

D + SoC

During chemotherapy (combination) stage: Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

SoC Alone

During chemotherapy (combination) stage: Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up. The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.

Analysis denominator · Participants

1. ci Lower Limit

   0.650

   ci Num Sides

   TWO_SIDED

   ci Pct Value

   95

   ci Upper Limit

   0.916

   estimate Comment

   The HR and CI were estimated from a stratified Cox proportional hazards model adjusting for PD-L1 (TC ≥50% vs \<50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using Efron method to control for ties.

   group Description

   T + D + SoC vs SoC alone. An HR \<1 favors T + D + SoC to be associated with a longer OS than SoC alone.

   group Ids

   1. OG000
   2. OG002

   non Inferiority Type

   SUPERIORITY

   p Value

   0.00304

   p Value Comment

   Analysis was performed using a stratified log-rank test adjusting for PD-L1 tumor expression (TC ≥50% vs \<50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using the Breslow approach for handling ties.

   param Type

   Hazard Ratio (HR)

   param Value

   0.77

   statistical Method

   Log Rank