A Study Evaluating the Safety and Efficacy of Neoadjuvant and Adjuvant Tiragolumab Plus Atezolizumab, With or Without Platinum-Based Chemotherapy, in Participants With Previously Untreated Locally Advanced Resectable Stage II, IIIA, or Select IIIB Non-Small Cell Lung Cancer
Phase 2
Completed
- Conditions
- Non-Small Cell Lung Cancer (NSCLC)
- Interventions
- Registration Number
- NCT04832854
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This study will evaluate the surgical safety and feasibility of atezolizumab plus tiragolumab alone or in combination with platinum-based chemotherapy as neoadjuvant treatment for participants with previously untreated locally advanced non-small cell lung cancer (NSCLC). The study will also evaluate the efficacy, pharmacokinetics, immunogenicity, and safety of atezolizumab plus tiragolumab alone or in combination with platinum-based chemotherapy as neoadjuvant treatment, followed by adjuvant atezolizumab plus tiragolumab or adjuvant platinum-based chemotherapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 50
Inclusion Criteria
Not provided
Exclusion Criteria
- NSCLC with histology of large cell neuroendocrine carcinoma, sarcomatoid carcinoma, or NSCLC not otherwise specified
- Small cell lung cancer (SCLC) histology or NSCLC with any component of SCLC
- Any prior therapy for lung cancer
- Active or history of autoimmune disease or immune deficiency
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
- Active tuberculosis
- Significant cardiovascular disease
- NSCLC with an activating EGFR mutation or ALK fusion oncogene
- Known c-ros oncogene 1 (ROS1) rearrangement
- History of malignancy other than NSCLC within 5 years prior to screening, with the exception of malignancies with 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
- Prior treatment with CD127 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, anti-TIGIT, and anti-PD-L1 therapeutic antibodies
- Treatment with systemic immunostimulatory agents
- Treatment with systemic immunosuppressive medication
- Pregnancy or breastfeeding
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort A (PD-L1 High) Tiragolumab Participants with high programmed death-ligand 1 (PD-L1) expression level will be enrolled in Cohort A and receive neoadjuvant atezolizumab plus tiragolumab for 4 cycles, followed by surgical resection and either adjuvant atezolizumab plus tiragolumab for 16 cycles or adjuvant chemotherapy for 4 cycles at the discretion of the investigator. Chemotherapy may include: * cisplatin/carboplatin + pemetrexed (for non-squamous only) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel Cohort B (PD-L1 All Comers) Tiragolumab All comers, which are participants with any PD-L1 expression level, will be enrolled in Cohort B and receive neoadjuvant atezolizumab plus tiragolumab plus chemotherapy for 4 cycles, followed by surgical resection and adjuvant atezolizumab plus tiragolumab for 16 cycles. Chemotherapy may include: * cisplatin/carboplatin + pemetrexed (for non-squamous only) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel Cohort A (PD-L1 High) Atezolizumab Participants with high programmed death-ligand 1 (PD-L1) expression level will be enrolled in Cohort A and receive neoadjuvant atezolizumab plus tiragolumab for 4 cycles, followed by surgical resection and either adjuvant atezolizumab plus tiragolumab for 16 cycles or adjuvant chemotherapy for 4 cycles at the discretion of the investigator. Chemotherapy may include: * cisplatin/carboplatin + pemetrexed (for non-squamous only) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel Cohort A (PD-L1 High) Carboplatin Participants with high programmed death-ligand 1 (PD-L1) expression level will be enrolled in Cohort A and receive neoadjuvant atezolizumab plus tiragolumab for 4 cycles, followed by surgical resection and either adjuvant atezolizumab plus tiragolumab for 16 cycles or adjuvant chemotherapy for 4 cycles at the discretion of the investigator. Chemotherapy may include: * cisplatin/carboplatin + pemetrexed (for non-squamous only) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel Cohort A (PD-L1 High) Pemetrexed Participants with high programmed death-ligand 1 (PD-L1) expression level will be enrolled in Cohort A and receive neoadjuvant atezolizumab plus tiragolumab for 4 cycles, followed by surgical resection and either adjuvant atezolizumab plus tiragolumab for 16 cycles or adjuvant chemotherapy for 4 cycles at the discretion of the investigator. Chemotherapy may include: * cisplatin/carboplatin + pemetrexed (for non-squamous only) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel Cohort A (PD-L1 High) Cisplatin Participants with high programmed death-ligand 1 (PD-L1) expression level will be enrolled in Cohort A and receive neoadjuvant atezolizumab plus tiragolumab for 4 cycles, followed by surgical resection and either adjuvant atezolizumab plus tiragolumab for 16 cycles or adjuvant chemotherapy for 4 cycles at the discretion of the investigator. Chemotherapy may include: * cisplatin/carboplatin + pemetrexed (for non-squamous only) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel Cohort A (PD-L1 High) Gemcitabine Participants with high programmed death-ligand 1 (PD-L1) expression level will be enrolled in Cohort A and receive neoadjuvant atezolizumab plus tiragolumab for 4 cycles, followed by surgical resection and either adjuvant atezolizumab plus tiragolumab for 16 cycles or adjuvant chemotherapy for 4 cycles at the discretion of the investigator. Chemotherapy may include: * cisplatin/carboplatin + pemetrexed (for non-squamous only) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel Cohort A (PD-L1 High) Paclitaxel Participants with high programmed death-ligand 1 (PD-L1) expression level will be enrolled in Cohort A and receive neoadjuvant atezolizumab plus tiragolumab for 4 cycles, followed by surgical resection and either adjuvant atezolizumab plus tiragolumab for 16 cycles or adjuvant chemotherapy for 4 cycles at the discretion of the investigator. Chemotherapy may include: * cisplatin/carboplatin + pemetrexed (for non-squamous only) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel Cohort B (PD-L1 All Comers) Atezolizumab All comers, which are participants with any PD-L1 expression level, will be enrolled in Cohort B and receive neoadjuvant atezolizumab plus tiragolumab plus chemotherapy for 4 cycles, followed by surgical resection and adjuvant atezolizumab plus tiragolumab for 16 cycles. Chemotherapy may include: * cisplatin/carboplatin + pemetrexed (for non-squamous only) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel Cohort B (PD-L1 All Comers) Pemetrexed All comers, which are participants with any PD-L1 expression level, will be enrolled in Cohort B and receive neoadjuvant atezolizumab plus tiragolumab plus chemotherapy for 4 cycles, followed by surgical resection and adjuvant atezolizumab plus tiragolumab for 16 cycles. Chemotherapy may include: * cisplatin/carboplatin + pemetrexed (for non-squamous only) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel Cohort B (PD-L1 All Comers) Carboplatin All comers, which are participants with any PD-L1 expression level, will be enrolled in Cohort B and receive neoadjuvant atezolizumab plus tiragolumab plus chemotherapy for 4 cycles, followed by surgical resection and adjuvant atezolizumab plus tiragolumab for 16 cycles. Chemotherapy may include: * cisplatin/carboplatin + pemetrexed (for non-squamous only) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel Cohort B (PD-L1 All Comers) Cisplatin All comers, which are participants with any PD-L1 expression level, will be enrolled in Cohort B and receive neoadjuvant atezolizumab plus tiragolumab plus chemotherapy for 4 cycles, followed by surgical resection and adjuvant atezolizumab plus tiragolumab for 16 cycles. Chemotherapy may include: * cisplatin/carboplatin + pemetrexed (for non-squamous only) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel Cohort B (PD-L1 All Comers) Gemcitabine All comers, which are participants with any PD-L1 expression level, will be enrolled in Cohort B and receive neoadjuvant atezolizumab plus tiragolumab plus chemotherapy for 4 cycles, followed by surgical resection and adjuvant atezolizumab plus tiragolumab for 16 cycles. Chemotherapy may include: * cisplatin/carboplatin + pemetrexed (for non-squamous only) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel Cohort B (PD-L1 All Comers) Paclitaxel All comers, which are participants with any PD-L1 expression level, will be enrolled in Cohort B and receive neoadjuvant atezolizumab plus tiragolumab plus chemotherapy for 4 cycles, followed by surgical resection and adjuvant atezolizumab plus tiragolumab for 16 cycles. Chemotherapy may include: * cisplatin/carboplatin + pemetrexed (for non-squamous only) * carboplatin + gemcitabine (for squamous only) * carboplatin + paclitaxel
- Primary Outcome Measures
Name Time Method Number of Participants With Surgical Delays Up to approximately 6 years Number of Participants With Operative and Post-operative Complications Up to approximately 6 years Number of Participants With Surgical Cancellations Related to Study Treatment Up to approximately 6 years Percentage of Participants With Adverse Events Up to approximately 6 years Percentage of Participants Who Achieve Major Pathological Response (MPR) At the time of surgery (approximately Weeks 17-20)
- Secondary Outcome Measures
Name Time Method Event Free Survival (EFS) From baseline to disease progression that precludes surgical resection, or local or distant disease recurrence after surgery, or death from any cause (up to approximately 6 years) Percentage of Participants With Anti-drug Antibodies (ADAs) to Atezolizumab Prior to the first infusion on Day 1 of Cycles 1, 2, 3, 4, 5, 8, 12 and 16 (cycle=21 days) and at TD visit (up to approximately 9 months) Percentage of Participants With Pathological Complete Response (pCR) At the time of surgery (approximately Weeks 17-20) Serum Concentrations of Tiragolumab Day 1 of Cycle 1 (cycle=21 days): pre-dose and 30 min post-dose; Day 1 of Cycles 2, 3, 4, 5, 8, 12, 16: pre-dose; at TD visit (up to approximately 9 months) Percentage of Participants With ADAs to Tiragolumab Prior to the first infusion on Day 1 of Cycles 1, 2, 3, 4, 5, 8, 12 and 16 (cycle=21 days) and at TD visit (up to approximately 9 months) Serum Concentrations of Atezolizumab Day 1 of Cycle 1 (cycle=21 days): pre-dose and 30 minutes (min) post-dose; Day 1 of Cycles 2, 3, 4, 5, 8, 12, 16: pre-dose; at treatment discontinuation (TD) visit (up to approximately 9 months)
Trial Locations
- Locations (22)
ICO L'Hospitalet
🇪🇸L Hospitalet De Llobregat, Barcelona, Spain
Kantonsspital St. Gallen
🇨🇭St. Gallen, Switzerland
UniversitätsSpital Zürich
🇨🇭Zürich, Switzerland
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Sunshine Coast University Hospital
🇦🇺Birtinya, Queensland, Australia
Peter Maccallum Cancer Institute
🇦🇺Melbourne, Victoria, Australia
Kantonsspital Baden
🇨🇭Baden, Switzerland
University of Southern California
🇺🇸Los Angeles, California, United States
Columbia University
🇺🇸New York, New York, United States
St. Vincent's Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Vall d?Hebron Institute of Oncology (VHIO), Barcelona
🇪🇸Barcelona, Spain
Corporacio Sanitaria Parc Tauli
🇪🇸Sabadell, Barcelona, Spain
Kantonsspital Graubünden Medizin Onkologie
🇨🇭Chur, Switzerland
City of Hope Cancer Center
🇺🇸Duarte, California, United States
Hospital Universitario Puerta de Hierro
🇪🇸Majadahonda, Madrid, Spain
Complejo Hospitalario Universitario A Coruña (CHUAC)
🇪🇸La Coruna, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Kantonsspital Winterthur
🇨🇭Winterthur, Switzerland
Winthrop Univ Hospital
🇺🇸Mineola, New York, United States
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
City of Hope at Irvine Lennar
🇺🇸Irvine, California, United States
NYU Cancer Center
🇺🇸New York, New York, United States