Phase 3
N=542
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
Non-small Cell Lung Cancer (NSCLC)
Bottom Line
View on ClinicalTrials.gov: NCT04619797 ↗Enrolled (actual)
542
Serious AEs
53.6%
Results posted
Jun 2026
Primary outcome: Primary: Progression-free Survival (PFS) as Determined by the Investigator — 9.89; 8.31 months — p=0.9912
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Tiragolumab (Drug); Atezolizumab (Drug); Pemetrexed (Drug); Carboplatin (Drug); Cisplatin (Drug); Tiragolumab Matching Placebo (Drug); Pembrolizumab (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Apr 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression-free Survival (PFS) as Determined by the Investigator |
9.89; 8.31 | 0.9912 |
| PRIMARY Overall Survival (OS) |
23.10; 18.89 | 0.9838 |
| SECONDARY PFS as Determined by the Independent Review Facility (IRF) |
— | — |
| SECONDARY Investigator Assessed PFS in Participants With PD-L1 Expression at TPS/TC >=1% |
11.96; 9.82 | 0.0488 sig |
| SECONDARY Investigator Assessed PFS in Participants With PD-L1 Expression at TPS/TC >=50% |
14.09; 11.76 | 0.2228 |
| SECONDARY OS in Participants With PD-L1 Expression at TPS/TC >=1% |
33.58; 20.70 | 0.0069 sig |
| SECONDARY OS in Participants With PD-L1 Expression at TPS/TC >= 50% |
33.58; 23.79 | 0.1810 |
| SECONDARY PFS Rate at Month 6 and Month 12 |
68.52; 61.12; 42.79; 34.26 | 0.0734 |
| SECONDARY OS Rate at Month 12 and Month 24 |
72.34; 63.38; 47.95; 41.90 | 0.0329 sig |
| SECONDARY Duration of Response (DOR) |
11.1; 9.4 | — |
| SECONDARY Objective Response Rate (ORR) |
56.6; 50.2 | 0.1220 |
| SECONDARY Time to Confirmed Deterioration (TTCD) in Participant-Reported Physical Functioning (PF) as Measured by European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC-QLQ-C30) |
30.36; 20.76 | 0.2613 |
| SECONDARY TTCD in Participant-Reported Global Health Status (GHS)/Quality of Life (QoL) as Measured by EORTC QLQ-C30 |
NA; NA | 0.0816 |
| SECONDARY TTCD in Participant-Reported Dyspnoea as Measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) |
16.99; 23.52 | 0.7727 |
| SECONDARY TTCD in Participant-Reported Chest Pain, as Measured by EORTC QLQ-LC13 |
NA; NA | 0.3694 |
| SECONDARY TTCD in Participant-Reported Cough, as Measured by EORTC QLQ-LC13 |
NA; NA | 0.1878 |
| SECONDARY Number of Participants With Adverse Events (AEs) |
267; 262 | — |
| SECONDARY Number of Participants With Response to Side Effects of Treatment as Assessed by European Organisation for Research and Treatment of Cancer Item List 46 (EORTC IL46) |
207; 192; 33; 44; 8; 12 | — |
| SECONDARY Serum Concentration of Atezolizumab |
NA; 326; 67.3; 106; 143; 173 | — |
| SECONDARY Serum Concentration of Tiragolumab |
NA; 137; 32.2; 51.2; 69.2; 79.6 | — |
| SECONDARY Number of Participants With Treatment-Emergent Anti-drug Antibodies (ADAs) to Atezolizumab |
90 | — |
| SECONDARY Number of Participants With Treatment-Emergent ADAs to Tiragolumab |
2 | — |
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).
Eligibility Criteria
Key Inclusion Criteria
- 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 Exclusion Criteria
- 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.
Data sourced from ClinicalTrials.gov (NCT04619797). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.