A Study of Tiragolumab in Combination With Atezolizumab Plus Pemetrexed and Carboplatin/Cisplatin Versus Pembrolizumab Plus Pemetrexed and Carboplatin/Cisplatin in Participants With Previously Untreated Advanced Non-Squamous Non-Small Cell Lung Cancer
- Conditions
- Non-small Cell Lung Cancer (NSCLC)
- Interventions
- Registration Number
- NCT04619797
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of tiragolumab in combination with atezolizumab plus pemetrexed and carboplatin/cisplatin (Arm A) compared with placebo in combination with pembrolizumab plus pemetrexed and carboplatin/cisplatin (Arm B) in participants with previously untreated, locally advanced unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC).
Eligible participants will be randomized in a 1:1 ratio to receive one of the following treatment regimens during the induction phase:
* Arm A: Tiragolumab plus atezolizumab plus pemetrexed and carboplatin or cisplatin
* Arm B: Placebo plus pembrolizumab plus pemetrexed and carboplatin or cisplatin
Following the induction phase, participants will continue maintenance therapy with either tiragolumab in combination with atezolizumab and pemetrexed (Arm A) or placebo in combination with pembrolizumab and pemetrexed (Arm B).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 542
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Histologically or cytologically documented locally advanced unresectable or metastatic non-squamous NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy
- No prior systemic treatment for metastatic non-squamous NSCLC
- Known tumor programmed death-ligand 1 (PD-L1) status
- Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
- Life expectancy >= 12 weeks
- Adequate hematologic and end-organ function
- Negative human immunodeficiency virus (HIV) test at screening
- Serology test negative for active hepatitis B virus or active hepatitis C virus at screening.
Key
- Mutations in epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma kinase (ALK) fusion oncogene
- Pulmonary lymphoepithelioma-like carcinoma subtype of NSCLC
- Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
- Active or history of autoimmune disease or immune deficiency
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
- History of malignancy other than NSCLC within 5 years prior to randomization, with the exception of malignancies with a negligible risk of metastasis or death
- Severe infection within 4 weeks prior to initiation of study treatment or any active infection that, in the opinion of the investigator, could impact patient safety
- Treatment with investigational therapy within 28 days prior to initiation of study treatment
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T lymphocyte-associated protein 4, anti-TIGIT, anti-PD-1, and anti-PD-L1 therapeutic antibodies
- Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
- Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment
- Known allergy or hypersensitivity or other contraindication to any component of the chemotherapy regimen the participant may receive during the study
- Women who are pregnant, or breastfeeding
- Known targetable c-ROS oncogene 1 (ROS1) or BRAFV600E genomic aberration.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tiragolumab+Atezolizumab+Pemetrexed+Carboplatin or Cisplatin Tiragolumab Induction treatment with tiragolumab in combination with atezolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with tiragolumab in combination with atezolizumab and pemetrexed on Day 1 of each 21-day cycle. Placebo+Pembrolizumab+Pemetrexed+Carboplatin or Cisplatin Tiragolumab Matching Placebo Induction treatment with placebo in combination with pembrolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with placebo in combination with pembrolizumab and pemetrexed on Day 1 of each 21-day cycle. Tiragolumab+Atezolizumab+Pemetrexed+Carboplatin or Cisplatin Atezolizumab Induction treatment with tiragolumab in combination with atezolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with tiragolumab in combination with atezolizumab and pemetrexed on Day 1 of each 21-day cycle. Tiragolumab+Atezolizumab+Pemetrexed+Carboplatin or Cisplatin Pemetrexed Induction treatment with tiragolumab in combination with atezolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with tiragolumab in combination with atezolizumab and pemetrexed on Day 1 of each 21-day cycle. Tiragolumab+Atezolizumab+Pemetrexed+Carboplatin or Cisplatin Carboplatin Induction treatment with tiragolumab in combination with atezolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with tiragolumab in combination with atezolizumab and pemetrexed on Day 1 of each 21-day cycle. Tiragolumab+Atezolizumab+Pemetrexed+Carboplatin or Cisplatin Cisplatin Induction treatment with tiragolumab in combination with atezolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with tiragolumab in combination with atezolizumab and pemetrexed on Day 1 of each 21-day cycle. Placebo+Pembrolizumab+Pemetrexed+Carboplatin or Cisplatin Pemetrexed Induction treatment with placebo in combination with pembrolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with placebo in combination with pembrolizumab and pemetrexed on Day 1 of each 21-day cycle. Placebo+Pembrolizumab+Pemetrexed+Carboplatin or Cisplatin Carboplatin Induction treatment with placebo in combination with pembrolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with placebo in combination with pembrolizumab and pemetrexed on Day 1 of each 21-day cycle. Placebo+Pembrolizumab+Pemetrexed+Carboplatin or Cisplatin Cisplatin Induction treatment with placebo in combination with pembrolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with placebo in combination with pembrolizumab and pemetrexed on Day 1 of each 21-day cycle. Placebo+Pembrolizumab+Pemetrexed+Carboplatin or Cisplatin Pembrolizumab Induction treatment with placebo in combination with pembrolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with placebo in combination with pembrolizumab and pemetrexed on Day 1 of each 21-day cycle.
- Primary Outcome Measures
Name Time Method Investigator-Assessed Progression-Free Survival (PFS) (Phase 2 and Phase 3) From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 5 years [Phase 2], up to approximately 7 years [Phase 3]) Investigator-Assessed Confirmed Objective Response Rate (ORR) (Phase 2) Up to approximately 5 years Overall Survival (Phase 3) From randomization to death from any cause (up to approximately 7 years)
- Secondary Outcome Measures
Name Time Method Overall Survival (Phase 2) From randomization to death from any cause (up to approximately 5 years) TTCD in Participant-Reported Lung Cancer Symptoms for Cough, Dyspnea, and Chest Pain, as Measured by EORTC QLQ-LC13 (Phase 2 and Phase 3) Up to approximately 5 years (Phase 2); up to approximately 7 years (Phase 3) TTCD using EORTC Quality-of-Life Questionnaire Lung Cancer Module (QLQ-LC13) is an initial 10-point increase in symptom score from baseline that must be held for at least two consecutive assessments or an initial clinically meaningful decrease above baseline followed by death. EORTC QLQ-LC13 consists of 13 lung cancer specific items and includes 11 disease-specific scales/items (dyspnea, coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, pain medication). Each item is scored on a 4-point scale of 1=Not at all to 4=Very much. Scores will be linearly transformed to a score range of 0 to 100. Higher score indicates worsening of symptoms.
PFS as Determined by an Independent Review Facility (IRF) (Phase 3) From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 7 years) Investigator-assessed PFS in Participants With PD-L1 Expression at TC ≥50% and TC ≥1% Cut-off, as Determined by Central Testing With Ventana PD-L1 (SP263) Assay (Phase 3) From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 7 years) OS in Participants With PD-L1 Expression at TC ≥50% and TC ≥1% Cut-off, as Determined by Central Testing With Ventana PD-L1 (SP263) Assay (Phase 3) From randomization to death from any cause (up to approximately 7 years) Investigator-Assessed PFS at 6 Months and 12 Months (Phase 3) 6 months, 12 months Serum Concentration of Tiragolumab (Phase 2 and Phase 3) Cycle 1 (each cycle=21 days), Day 1: predose, 0.5 hour (h) postdose; Cycles 2, 3, 4, 8, 12, 16, Day 1: predose and at treatment discontinuation (TD) visit (up to approximately 5 years [Phase 2]; up to approximately 7 years [Phase 3]) OS Rate at 12 Months and 24 Months (Phase 3) 12 months, 24 months Investigator-Assessed Confirmed ORR (Phase 3) Up to approximately 7 years Investigator-Assessed Duration of Response (DOR) (Phase 2 and Phase 3) From first occurrence of a documented confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 5 years [Phase 2]; up to approximately 7 years [Phase 3]) Percentage of Participants With Adverse Events (AEs) (Phase 2 and Phase 3) Up to approximately 5 years (Phase 2); up to approximately 7 years (Phase 3) Participants' Response to Side Effects of Treatment as Assessed by EORTC IL46 (Phase 2 and Phase 3) Up to approximately 5 years (Phase 2); up to approximately 7 years (Phase 3) EORTC Item List 46 (IL46) is a validated single-item question that assesses overall side effect impact. Each item is scored on a 4-point scale of 1=Not at all to 4=Very much. Scores will be linearly transformed to a score range of 0 to 100. Higher score indicates a worse outcome.
Serum Concentration of Atezolizumab (Phase 2 and Phase 3) Cycle 1 (each cycle=21 days), Day 1: predose, 0.5 hour (h) postdose; Cycles 2, 3, 4, 8, 12, 16, Day 1: predose and at TD visit (up to approximately 5 years [Phase 2]; up to approximately 7 years [Phase 3]) Time to Confirmed Deterioration (TTCD) in Participant-Reported Physical Functioning and Global Health Status (GHS)/Quality of Life (QoL) as Measured by European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 (Phase 2 and Phase 3) Up to approximately 5 years (Phase 2); up to approximately 7 years (Phase 3) TTCD using EORTC Quality-of-Life Questionnaire Core 30 (QLQ-C30) is an initial 10-point decrease in GHS and physical functioning from baseline that must be held for at least two consecutive assessments or an initial clinically meaningful decrease above baseline followed by death. EORTC QLQ-C30: a self-reported measure, consisting of 30 questions that assess 5 aspects of participants functioning (physical, emotional, role, cognitive and social), 3 symptom scales (fatigue, nausea/vomiting and pain), GHS and QoL, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) with a recall period of the previous week. Functioning items are scored on a 4-point scale: 1=Not at all to 4=Very much, with higher score indicating worse outcome. Symptom items (GHS and QoL) are scored on a 7-point scale: 1=Very poor to 7=Excellent. Scores will be linearly transformed with a minimum score of 0 and maximum score of 100. Higher score indicates better outcome.
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab (Phase 2 and Phase 3) Predose on Day 1 of Cycles (each cycle=21 days) 1, 2, 3, 4, 8, 12, 16 and at TD visit (up to approximately 5 years [Phase 2]; up to approximately 7 years [Phase 3]) Percentage of Participants With ADAs to Atezolizumab (Phase 2 and Phase 3) Predose on Day 1 of Cycles (each cycle=21 days) 1, 2, 3, 4, 8, 12, 16 and at TD visit (up to approximately 5 years [Phase 2]; up to approximately 7 years [Phase 3])
Trial Locations
- Locations (122)
UCLA
🇺🇸Los Angeles, California, United States
Torrance Memorial Physician Network/Cancer Care
🇺🇸Torrance, California, United States
PIH Health Whittier Hospital
🇺🇸Whittier, California, United States
SCRI Florida Cancer Specialists South
🇺🇸Fort Myers, Florida, United States
SCRI Florida Cancer Specialists North
🇺🇸Saint Petersburg, Florida, United States
Advent Health Orlando
🇺🇸Winter Park, Florida, United States
Northwest Georgia Oncology Centers PC - Marietta
🇺🇸Marietta, Georgia, United States
Fort Wayne Medical Oncology and Hematology, Inc
🇺🇸Fort Wayne, Indiana, United States
Baptist Health Lexington
🇺🇸Lexington, Kentucky, United States
Tennessee Oncology Chattanooga
🇺🇸Chattanooga, Tennessee, United States
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