臨床研究等提出・公開システム

A Phase III, Randomized, Multi-Center, Open-Label, Comparative Global Study to Determine the Efficacy of Durvalumab or Durvalumab and Tremelimumab in Combination With Platinum-Based Chemotherapy for First-Line Treatment in Patients With Metastatic Non Small-Cell Lung Cancer (NSCLC)

POSEIDON

1186

- Arm/Group Description 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. Total: Total of all reporting groups - Overall Number of Baseline Participants T + D + SoC: 338 participants D + SoC: 338 participants SoC Alone: 337 participants Total : 1013 participants - Baseline Analysis Population Description Global cohort: All patients in the full analysis set (FAS), which included all randomized patients, were included in the baseline analysis. Patients were included in the analysis in the treatment arm to which they were randomized, regardless of the treatment they received. - Age, Continuous Mean (Standard Deviation) Unit of measure: Years T + D + SoC: Number Analyzed 338 participants, 62.6(9.43) D + SoC: Number Analyzed 338 participants, 63.5(9.10) SoC Alone: Number Analyzed 337 participants, 63.1(9.87) Total: Number Analyzed 1013 participants, 63.1(9.47) - Sex: Female, Male Measure Type: Count of Participants, Unit of measure: Participants T + D + SoC: Number Analyzed 338 participants, Female 69(20.4%), Male 269(79.6%) D + SoC: Number Analyzed 338 participants, Female 85(25.1%), Male 253(74.9%) SoC Alone: Number Analyzed 337 participants, Female 89(26.4%), Male 248(73.6%) Total: Number Analyzed 1013 participants, Female 243(24.0%), Male 770(76.0%) - Race/Ethnicity, Customized Measure Type: Count of Participants, Unit of measure: Participants T + D + SoC: Number Analyzed 338 participants, White 205(60.7%), Black or African American 8(2.4%), Asian 99(29.3%), Native Hawaiian or other Pacific Islander 2(0.6%), American Indian or Alaska Native 12(3.6%), Other 12(3.6%) D + SoC: Number Analyzed 338 participants, White 182(53.8%), Black or African American 4(1.2%), Asian 123(36.4%), Native Hawaiian or other Pacific Islander 0(0%), American Indian or Alaska Native 17(5.0%), Other 13(3.9%) SoC Alone: Number Analyzed 337 participants, White 179(53.1%), Black or African American 8(2.4%), Asian 128(38.0%), Native Hawaiian or other Pacific Islander 0(0%), American Indian or Alaska Native 9(2.7%), Other 13(3.9%) Total: Number Analyzed 1013 participants, White 566(55.9%), Black or African American 20(2.0%), Asian 350(34.6%), Native Hawaiian or other Pacific Islander 2(0.2%), American Indian or Alaska Native 38(3.8%), Other 37(3.7%) - Race/Ethnicity, Customized Measure Type: Count of Participants, Unit of measure: Participants T + D + SoC: Number Analyzed 338 participants, Hispanic or Latino 51(15.1%), Not Hispanic or Latino 287(84.9%) D + SoC: Number Analyzed 338 participants, Hispanic or Latino 54(16.0%), Not Hispanic or Latino 284(84.0%) SoC Alone: Number Analyzed 337 participants, Hispanic or Latino 55(16.3%), Not Hispanic or Latino 282(83.7%) Total: Number Analyzed 1013 participants, Hispanic or Latino 160(15.8%), Not Hispanic or Latino 853(84.2%) - Age Cateegorical Measure Type: Count of Participants, Unit of measure: Participants T + D + SoC: Number Analyzed 338 participants, 18 or more to 50 29(8.6%),

- Recruitment Details Study was conducted in 142 study centers across 18 countries in North and Latin America, Europe, Asia Pacific and Africa. First patient randomized: 27 June 2017. Results are presented for the global cohort at final analysis data cut-offs (DCOs) of 24 July 2019 (Response Evaluation Criteria in Solid Tumors [RECIST]-based endpoints) and 12 March 2021 (all other data). Once global enrollment was complete, enrollment was started in mainland China. Results for the China cohort will be reported later. - Pre-assignment Details Patients were randomized in a stratified manner as per programmed cell death ligand 1 (PD-L1) tumor expression status (PD-L1 tumor cells [TC] 50% or more versus [vs] <50%), disease stage (IVA vs IVB), and histology (non-squamous vs squamous) in a 1:1:1 ratio to receive treatment with tremelimumab + durvalumab combination therapy + standard of care (SoC) chemotherapy (also referred to as T + D + SoC), durvalumab monotherapy + SoC chemotherapy (also referred to as D + SoC), or SoC chemotherapy alone. - Overall Study T + D + SoC: Started[1] 338, Received Treatment 331, Completed[2] 80, Not Completed 258 D + SoC: Started[1] 338, Received Treatment 335, Completed[2] 65, Not Completed 273 SoC Alone: Started[1] 337, Received Treatment 331, Completed[2] 40, Not Completed 297 - Reason Not Completed T + D + SoC: Death 250, Lost to Follow-up 2, Withdrawal by Subject 6 D + SoC: Death 264, Lost to Follow-up 2, Withdrawal by Subject 7 SoC Alone: Death 279, Lost to Follow-up 2, Withdrawal by Subject 16 [1] Randamized and included in global cohort analysis [2] Completed study or ongoing in study at primary completion date (global cohort final analysis DCO of 12 March 2021)

- Time Frame: Adverse events: from first dose of study treatment until the earlier of 90 days after last dose or the date of first subsequent anticancer therapy. All-cause mortality (death due to any cause): from randomization up to global cohort final analysis DCO (12 March 2021). Maximum timeframe of approximately 45 months. - Adverse Event Reporting Description: Safety analysis set included all patients who received at least 1 dose of study treatment (analyzed according to actual treatment received). 1 patient randomized to T + D + SoC arm and 1 patient randomized to D + SoC arm only received SoC and were included in SoC alone arm of the safety analysis set. All-cause mortality was determined for patients in the FAS (analyzed according to randomized treatment arm, regardless of the treatment received). Results are reported for the global cohort only. - All-Cause Mortality T + D + SoC: 251/338 (74.26%) D + SoC: 265/338 (78.40%) SoC Alone: 285/337 (84.57%) - Serious Adverse Events T + D + SoC: Serious adverse events were confirmed in 146 out of 330 individuals (44.24%). The specific events are as follows. For detailed event names and their frequencies, please refer to the Results Posted on ClinicalTrials.gov for the Study of Durvalumab + Tremelimumab With Chemotherapy or Durvalumab With Chemotherapy or Chemotherapy Alone for Patients With Lung Cancer (POSEIDON) (page in English). Hematologic and Lymphatic Disorders: Reports include leukopenia, anemia, and neutropenia. Cardiac Disorders: Observations include myocardial infarction, atrial fibrillation, and heart failure. Ear and Labyrinth Disorders: There is one report of unilateral hearing loss. Endocrine Disorders: Observations include adrenal insufficiency and diabetes insipidus. Gastrointestinal Disorders: Multiple reports of issues related to the digestive system, such as diarrhea and colitis. General Disorders: Includes fever and sudden death. Hepatobiliary Disorders: Includes drug-induced liver injury and autoimmune hepatitis. Infectious Diseases: Many infections have been noted, including pneumonia, COVID-19, and pneumocystis pneumonia. Renal and Urinary Disorders: Reports of acute renal injury and renal failure. Respiratory Disorders: Pneumonia and pulmonary embolism are frequently observed. Skin Disorders: Reports include rashes and drug eruptions. D + SoC: Serious adverse events were confirmed in 134 out of 334 individuals (40.12%). The specific events are as follows. For detailed event names and their frequencies, please refer to the Results Posted on ClinicalTrials.gov for the Study of Durvalumab + Tremelimumab With Chemotherapy or Durvalumab With Chemotherapy or Chemotherapy Alone for Patients With Lung Cancer (POSEIDON) (page in English). Hematologic and Lymphatic Disorders: Anemia is the most common, with neutropenia and thrombocytopenia also observed. Cardiac Disorders: Reports include acute myocardial infarction, atrial fibrillation, and cardiac tamponade, but acute coronary syndrome has not been observed. Ear and Labyrinth Disorders: One case of bilateral hearing loss has been reported. Endocrine Disorders: Multiple cases of adrenal insufficiency have been observed. Gastrointestinal Disorders: Reports include abdominal discomfort, diarrhea, and colitis, as well as gastrointestinal bleeding and bowel obstruction. General Disorders: Includes death, sudden death, and asthenia, with reports of fatigue and malaise. Hepatobiliary Disorders: Cholangitis and autoimmune hepatitis have been observed. Immune System Disorders: Anaphylactic reactions and hypersensitivity are observed. Infections and Infestations: Pneumonia is predominant, including COVID-19 and related pneumonia. Injury, Poisoning, and Procedural Complications: Hip fractures and radiation esophagitis have been reported. Blood tests: Increasing liver enzymes and decreased white blood cell count are observed. Metabolism and Nutrition Disorders: Include hyperglycemia and hypokalemia. Musculoskeletal and Connective Tissue Disorders: Include back pain and joint pain. Neoplasms Benign, Malignant and Unspecified: Include cancer-related pain and colorectal cancer. Nervous System Disorders: Stroke and a small number of seizures are reported. Psychiatric Disorders: One case of completed suicide has been reported. Renal and Urinary Disorders: Acute kidney injury and glomerulonephritis are observed. Respiratory, Thoracic and Mediastinal Disorders: Hemoptysis and pneumonia are prominent, with aspiration pneumonia also included. Skin and Subcutaneous Tissue Disorders: Two cases of rash are confirmed. Vascular Disorders: Include embolism and hemorrhagic shock. SoC Alone: Serious adverse events were confirmed in 117 out of 333 individuals (35.14%). The specific events are as follows. For detailed event names and their frequencies, please refer to the Results Posted on ClinicalTrials.gov for the Study of Durvalumab + Tremelimumab With Chemotherapy or Durvalumab With Chemotherapy or Chemotherapy Alone for Patients With Lung Cancer (POSEIDON) (page in English). Hematologic and Lymphatic Disorders: Anemia is the most common, with reports of neutropenia and thrombocytopenia as well. Disseminated intravascular coagulation syndrome and febrile neutropenia are also observed. Cardiac Disorders: Acute myocardial infarction, angina, and heart failure are reported. Tachyarrhythmias and ventricular fibrillation are also noted in a small number. Ear and Labyrinth Disorders: No specific reports are present. Endocrine Disorders: No relevant reports are present. Eye Disorders: Cataracts have been reported. Gastrointestinal Disorders: Include diarrhea, gastric ulcer bleeding, nausea, pancreatitis, and esophagitis, although widespread reports are few. General Disorders: Include asthenia, facial edema, and fever, with only one report of death. Hepatobiliary Disorders: One case of liver failure is reported. Immune System Disorders: There is one report of drug hypersensitivity. Infections and Infestations: Multiple reports of cellulitis and pneumonia, including COVID- 19 pneumonia, are observed. Injury, Poisoning, and Procedural Complications: Reports include hip fractures and upper limb fractures. Blood tests: Decreases in neutrophil and platelet counts are confirmed. Metabolism and Nutrition Disorders: Include few reports of dehydration, hypercalcemia, and hyponatremia. Musculoskeletal and Connective Tissue Disorders: Include joint pain and musculoskeletal chest pain. Neoplasms Benign, Malignant, and Unspecified: Reports include rectal cancer. Nervous System Disorders: Reports include stroke, spinal cord disorders, and headaches. Psychiatric Disorders: No specific reports are present. Renal and Urinary Disorders: Include acute kidney injury and chronic kidney disease, but the number of reports is low. Respiratory, Thoracic, and Mediastinal Disorders: Chronic obstructive pulmonary disease and pulmonary embolism are frequently reported. Skin and Subcutaneous Tissue Disorders: No specific reports are present. Vascular Disorders: Reports of deep vein thrombosis and hemorrhagic shock exist but are infrequent.

1. Progression-Free Survoval (PFS); D + SoC Compared With SoC Alone Type: Primary / Time Frame: Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months). - Description PFS (per RECIST version 1.1 [RECIST 1.1] using Blinded Independent Central Review [BICR] assessments) was defined as time from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression. Median PFS was calculated using the Kaplan-Meier technique. The final analysis of PFS in the global cohort was pre-specified after approximately 497 BICR PFS events occurred across the D + SoC and SoC alone treatment arms (75% maturity). - Time Frame Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months). - Analysis Population Description Global cohort: The FAS included all randomized patients. Analysis of PFS was assessed as a primary outcome measure for comparison of the D + SoC vs SoC alone treatment arms only. The alternative treatment arm comparisons were assessed as a secondary outcome measure. - Overall Number of Participants Analyzed D + SoC 338, SoC Alone 337 - Median (95% Confidence Interval) | Unit of Measure: months D + SoC 5.5 (4.7 to 6.5), SoC Alone 4.8 (4.6 to 5.8) Statistical Analysis 1 - Statistical Analysis Overview Comparison Group Selection: D + SoC, SoC Alone Comments: D + SoC vs SoC alone. A hazard ratio (HR) <1 favors D + SoC to be associated with a longer PFS than SoC alone. Type of Statistical Test: Superiority Comments: [Not Specified] - Statistical Test of Hypothesis P-Value: 0.00093 Comments: Analysis was performed using a stratified log-rank test adjusting for PD-L1 tumor expression (TC 50% or more vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using the Breslow approach for handling ties. Method: Log Rank Comments: [Not Specified] - Method of Estimation Estimation Parameter: Hazard Ratio (HR) Estimated Value: 0.74 Confidence Interval: (2-Sided) 95% 0.620 to 0.885 Estimation Comments: The HR and confidence interval (CI) were estimated from a stratified Cox proportional hazards model adjusting for PD-L1 (TC 50% or more vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using Efron method to control for ties. 2. Overall Survival (OS); D + SoC Compared With SoC Alone Type: Primary / Time Frame: From baseline until death due to any cause. Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months). - Description OS was defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. The final analysis of OS in the global cohort was pre-specified after approximately 532 OS events occurred across the D + SoC and SoC alone treatment arms (80% maturity). - Time Frame From baseline until death due to any cause. Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months). - Analysis Population Description Global cohort: The FAS included all randomized patients. Analysis of OS was assessed as a primary outcome measure for comparison of the D + SoC vs SoC alone treatment arms only. The alternative treatment arm comparisons were assessed as a secondary outcome measure. - Overall Number of Participants Analyzed D + SoC 338, SoC Alone 337 - Median (95% Confidence Interval) / Unit of Measure: months D + SoC 13.3 (11.4 to 14.7), SoC Alone 11.7 (10.5 to 13.1) Statistical Analysis 1 - Statistical Analysis Overview Comparison Group Selection: D + SoC, SoC Alone Comments: D + SoC vs SoC alone. An HR <1 favors D + SoC to be associated with a longer OS than SoC alone. Type of Statistical Test: Superiority Comments: [Not Specified] - Statistical Test of Hypothesis P-Value: 0.07581 Comments: Analysis was performed using a stratified log-rank test adjusting for PD-L1 tumor expression (TC 50% or more vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using the Breslow approach for handling ties. Method: Log Rank Comments: [Not Specified] - Method of Estimation Estimation Parameter: Hazard Ratio (HR) Estimated Value: 0.86 Confidence Interval: (2-Sided) 95% 0.724 to 1.016 Estimation Comments: The HR and CI were estimated from a stratified Cox proportional hazards model adjusting for PD-L1 (TC 50% or more vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using Efron method to control for ties.

3.PFS; Comparison between T + D + SoC and SoC Alone, and T + D + SoC and D + SoC In the PFS (Progression-Free Survival) study, T+ D + SoC, and SoC Alone were compared over a follow-up of up to 25 months. Randomized patients underwent tumor scans at baseline, week 6, week 12, and every 8 weeks thereafter. Total participants: T + D + SoC 338, D + SoC 338, SoC Alone 337. Median PFS: T + D + SoC 6.2 months, D + SoC 5.5 months, SoC Alone 4.8 months. Statistical analysis suggests that T + D + SoC has a longer PFS than SoC Alone with HR of 0.72 (95% CI: 0.600-0.860), P-value 0.00031, using stratified log-rank test based on PD-L1 expression, histology, and disease stage. 4.OS; Comparison between T + D + SoC and SoC Alone, and T + D + SoC and D + SoC The OS (Overall Survival) comparison analyzed the three treatment groups: T + D + SoC, D + SoC, and SoC Alone over a follow-up of up to 45 months. Median OS calculated using the Kaplan-Meier method: T + D + SoC 14.0 months, D + SoC 13.3 months, SoC Alone 11.7 months. T + D + SoC showed longer OS than SoC Alone with HR 0.77 (95% CI: 0.650-0.916), P-value 0.00304, using stratified log-rank test based on PD-L1 expression, histology, and disease stage. 5.Objective Response Rate (ORR) ORR is defined as the proportion of patients with a complete response (CR) or partial response (PR). Tumor scans were conducted for up to 25 months. Total analyzed: T + D + SoC 335, D + SoC 330, SoC Alone 332. ORR was 46.3% for T + D + SoC, 48.5% for D + SoC, and 33.4% for SoC Alone. Statistical analysis showed an odds ratio of 1.72 (95% CI: 1.260-2.367) favoring D + SoC over SoC Alone, using logistic regression based on PD-L1 expression, histology, and disease stage. 6.Best Objective Response Rate (BoR) BoR is defined as the best response shown by patients based on RECIST 1.1 evaluation. Tumor scans conducted for up to 25 months. Total analyzed: T + D + SoC 335, D + SoC 330, SoC Alone 332. CR: T + D + SoC 0.6%, D + SoC 0.9%, SoC Alone 0%. PR: T + D + SoC 45.7%, D + SoC 47.6%, SoC Alone 33.4%. Stable Disease (SD) for over 6 weeks: T + D + SoC 35.8%, D + SoC 32.4%, SoC Alone 45.2%. Progressive Disease (PD): T + D + SoC 14.3%, D + SoC 18.2%, SoC Alone 18.4%. Not Evaluable (NE): T + D + SoC 3.6%, D + SoC 0.9%, SoC Alone 3.0%. 7.Duration of Response (DoR) DoR refers to the period from the first response until recorded disease progression or death. Tumor scans conducted for up to 25 months. Total analyzed: T + D + SoC 155, D + SoC 160, SoC Alone 111. Median DoR: T + D + SoC 7.4 months (3.5-NA), D + SoC 6.0 months (3.4-NA), SoC Alone 4.2 months (3.0-6.9). 8.Time from Randomization to Second Progression (PFS2) PFS2 indicates the time from randomization to the second progression event or death. Tumor scans conducted up to 25 months involving all patients. Participants: T + D + SoC 338, D + SoC 338, SoC Alone 337. Medians: T + D + SoC 10.4 months, D + SoC 10.2 months, SoC Alone 9.4 months. Statistical analysis showed HR of 0.79 (95% CI: 0.666-0.928) for D + SoC and 0.75 (95% CI: 0.632-0.883) for T + D + SoC, both indicating longer PFS2 than SoC Alone. 9.Pharmacokinetics (PK) of Durvalumab; Serum Peak and Trough Concentrations The PK of durvalumab was assessed by measuring serum peak and trough concentrations. Samples collected at week 0, week 3, week 12, and follow-up. Analyzed in T + D + SoC and D + SoC groups. Peak at week 0: T + D + SoC 418.80 mcg/mL, D + SoC 505.01 mcg/mL. Trough at week 3: T + D + SoC 82.08 mcg/mL, D + SoC 91.53 mcg/mL. Week 12: T + D + SoC 195.62 mcg/mL, D + SoC 212.11 mcg/mL. Follow-up: T + D + SoC 13.42 mcg/mL, D + SoC 16.06 mcg/mL. 10.Pharmacokinetics (PK) of Tremelimumab; Serum Peak and Trough Concentrations The PK of tremelimumab was assessed by measuring serum peak and trough concentrations. Samples collected at week 0, week 3, week 12, and follow-up, with evaluation conducted in 327 T + D + SoC group participants. Peak at week 0 was 23.17 mcg/mL, week 3 trough was 4.16 mcg/mL, week 12 was 7.82 mcg/mL, follow-up was 0.86 mcg/mL. 11.Number of Patients with Anti-Drug Antibody (ADA) Response to Durvalumab ADA samples were collected on day 1, at week 12, and three months post-treatment end. ADA prevalence: 42 (14.7%) in T + D + SoC group of 286, 33 (11.6%) in D + SoC group of 285. Treatment-emergent ADA incidence: 29 (10.1%) in T + D + SoC and 19 (6.7%) in D + SoC. Persistent ADA positive: T + D + SoC 8 (2.8%), D + SoC 7 (2.5%). nAb positive reported in 3 patients each group. 12.Number of Patients with ADA Response to Tremelimumab Samples were collected at day 1, week 12, and three months post-treatment. ADA prevalence in T + D + SoC only was 41 (15.8%). Treatment-emergent ADA: 38 (13.7%). Boosted ADA: 3 (1.1%). Induced ADA: 35 (12.6%). Persistent ADA: 22 (7.9%). Temporary: 18 (6.5%). nAb positive: 31 (11.2%). 13.Overall Health/Health-Related Quality of Life (HRQoL) and Time to Worsening of Patient-Reported Outcomes (PRO) Symptoms, Assessed Using the EORTC QLQ HRQoL and PRO were evaluated using the EORTC QLQ-C30. Maximum 45 months follow-up including T + D + SoC 325, D + SoC 326, SoC Alone 321. QLQ-C30 global health median: T + D + SoC 8.3 months, D + SoC 7.8 months, SoC Alone 5.6 months. Assessed physical, role, cognitive, emotional, social functions and symptoms (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea). 14.Time to Worsening of Lung Cancer-Specific PRO Symptoms Using EORTC QLQ-LC13 Assessed using the EORTC QLQ-LC13 module over up to 45 months. T + D + SoC 325, D + SoC 326, SoC Alone 321. Median symptom worsening: cough T + D + SoC 9.7 months, D + SoC 11.0 months, SoC Alone 8.8 months. Hemoptysis: T + D + SoC 17.8 months, D + SoC 14.0 months, SoC Alone 11.4 months. Dyspnea: T + D + SoC 5.4 months, D + SoC 5.0 months, SoC Alone 3.6 months. Chest pain: T + D + SoC 10.0 months, D + SoC 9.5 months, SoC Alone 8.6 months. Overall, T + D + SoC showed slower symptom worsening. **For detailed data in terms of section3 to 14, please refer to the Results Posted on ClinicalTrials.gov for the Study of Durvalumab + Tremelimumab With Chemotherapy or Durvalumab With Chemotherapy or Chemotherapy Alone for Patients With Lung Cancer (POSEIDON) (page in English).

Limitations and Caveats This study also incorporates a China tail, comprising additional patients randomized after the end of the global cohort recruitment. Efficacy and safety of patients randomized in China will be reported at a later date once this separate analysis has been completed.

Jan. 06, 2025

Feb. 20, 2023

https://pubmed.ncbi.nlm.nih.gov/36327426/

Yes

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this dose not mean all request will be approved.

Hibi Kazushige

Astrazeneka K.K

3-1, Ofuka-cho, Kita-ku, Osaka-shi, Osaka

RD-clinical-information-Japan@astrazeneca.com

Hibi Kazushige

Astrazeneka K.K

3-1, Ofuka-cho, Kita-ku, Osaka-shi, Osaka

+81-6-4802-3533

RD-clinical-information-Japan@astrazeneca.com

completed

June. 01, 2017

Interventional

Randomized, Parallel Assignment, No masking

treatment purpose

3

1. Aged at least 18 years.

2. Histologically or cytologically documented Stage IV NSCLC.

3. Confirmed tumor PD-L1 status prior to randomization.

4. Patients must have tumors that lack activating EGFR mutations and ALK fusions.

5. No prior chemotherapy or any other systemic therapy for metastatic NSCLC.

6. World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

7. No prior exposure to immunemediated therapy, excluding therapeutic anticancer vaccines.

1. Mixed small-cell lung cancer and NSCLC histology, sarcomatoid variant.

2. Active or prior documented autoimmune or inflammatory disorders.

3. Brain metastases or spinal cord compression unless the patient's condition is stable and off steroids.

4. Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus.

Both

Non Small Cell Lung Cancer NSCLC

investigational material(s)
Generic name etc : Durvalumab, Tremelimumab, Abraxane + carboplatin, Gemcitabine + cisplatin, Gemcitabine + carboplatin, Pemetrexed + carboplatin, Pemetrexed + cisplatin
INN of investigational material :
Therapeutic category code : 42- Antineoplastic agents
Dosage and Administration for Investigational material : [Durvalumab] IV infusions every 3 weeks for 12 weeks (4 cycles) and every 4 weeks thereafter until disease progression or other discontinuation criteria [Tremelimumab] IV infusions every 3 weeks for 12 weeks (4 cycles). An additional dose of tremelimumab will be administered in the week 16. [Abraxane + carboplatin] Standard of care chemotherapy (squamous and non-squamous patients) [Gemcitabine + cisplatin] Standard of care chemotherapy (squamous patients only) [Gemcitabine + carboplatin] Standard of care chemotherapy (squamous patients only) [Pemetrexed + carboplatin] Standard of care chemotherapy (non-squamous patients only) [Pemetrexed + cisplatin] Standard of care chemotherapy (non-squamous patients only)

[Current]
- Progression-Free Survival (PFS); D + SoC Compared With SoC Alone [Time Frame: Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months).]

- PFS (per RECIST version 1.1 [RECIST 1.1] using Blinded Independent Central Review [BICR] assessments) was defined as time from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression. Median PFS was calculated using the Kaplan-Meier technique. The final analysis of PFS in the global cohort was pre-specified after approximately 497 BICR PFS events occurred across the D + SoC and SoC alone treatment arms (75% maturity).

- Overall Survival (OS); D + SoC Compared With SoC Alone [Time Frame: From baseline until death due to any cause. Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months).]

- OS was defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. The final analysis of OS in the global cohort was pre-specified after approximately 532 OS events occurred across the D + SoC and SoC alone treatment arms (80% maturity).

[Original]
Progression-free survival (PFS) using Blinded Independent Central Review (BICR) assessments according to RECIST 1.1 [Time Frame: Up to 3 years after first patient randomized]

+81-827-34-1000

Aug. 03, 2017