Back to resultsA 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
Primary Purpose
Non-Small Cell Lung Cancer (NSCLC)
Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Atezolizumab
Tiragolumab
Carboplatin
Cisplatin
Pemetrexed
Gemcitabine
Paclitaxel
Sponsored by
About this trial
This is an interventional treatment trial for Non-Small Cell Lung Cancer (NSCLC)
Eligibility Criteria
Key inclusion criteria:
- Histologically or cytologically confirmed Stage II, IIIA, or select IIIB (T3N2 only) NSCLC of squamous or non-squamous histology
- Eligible for R0 resection with curative intent at the time of screening
- Adequate pulmonary function to be eligible for surgical resection with curative intent
- Eligible to receive a platinum-based chemotherapy regimen
- Measurable disease, as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Availability of a representative tumor specimen that is suitable for determination of PD-L1 status
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Normal life expectancy, excluding lung cancer mortality risk
- Adequate hematologic and end-organ function
- Negative human immunodeficiency virus (HIV) test at screening
- Negative serology for active hepatitis B virus (HBV) and active hepatitis C virus (HCV) at screening
Key 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
Sites / Locations
- City of Hope Cancer Center; Division of Medical Oncology & Experimental Therapeutics
- City of Hope at Irvine Lennar
- University of Southern California
- USC Norris Cancer Center; Oncology/Hematology - Newport Beach Treatment Center
- Georgetown U; Lombardi Comp Can
- University of Kansas Cancer Center
- Washington University School of Medicine; Medical Oncology
- Winthrop Univ Hospital
- NYU Cancer Center
- Columbia University
- Mays Cancer Center
- Sunshine Coast University Hospital; The Adem Crosby Centre
- Cabrini Hospital Malvern
- PETER MACCALLUM CANCER INSTITUTE; MEDICAL ONCOLOGY; Parkville Cancer Clinical Trials Unit
- Kosin University Gospel Hospital
- St. Vincent's Hospital
- Seoul National University Hospital
- Severance Hospital, Yonsei University Health System
- ICO L'Hospitalet; Servicio de oncologia medica
- Corporacio Sanitaria Parc Tauli; Servicio de Oncologia
- Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Oncologia
- Hospital Universitario Puerta de Hierro; Servicio de Oncologia
- Vall d?Hebron Institute of Oncology (VHIO), Barcelona
- Hospital Universitario 12 de Octubre; Servicio de Oncologia
- Kantonsspital Baden; Medizinische Klinik, Onkologie
- Universitaetsspital Basel; Onkologie
- Kantonsspital Graubünden Medizin Onkologie; Onkologie und Hämatologie
- Kantonsspital St. Gallen; Onkologie/Hämatologie
- Kantonsspital Winterthur; Medizinische Onkologie
- UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort A (PD-L1 High)
Cohort B (PD-L1 All Comers)
Arm Description
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) cisplatin/carboplatin + gemcitabine (for squamous only) carboplatin + 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) cisplatin/carboplatin + gemcitabine (for squamous only) carboplatin + paclitaxel
Outcomes
Primary Outcome Measures
Number of Participants With Surgical Delays
Number of Participants With Operative and Post-operative Complications
Number of Participants With Surgical Cancellations Related to Study Treatment
Percentage of Participants With Adverse Events
Percentage of Participants Who Achieve Major Pathological Response (MPR)
Secondary Outcome Measures
Percentage of Participants With Pathological Complete Response (pCR)
Event Free Survival (EFS)
Serum Concentrations of Atezolizumab
Serum Concentrations of Tiragolumab
Percentage of Participants With Anti-drug Antibodies (ADAs) to Atezolizumab
Percentage of Participants With ADAs to Tiragolumab
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04832854
Brief Title
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
Official Title
A Phase II, Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Neoadjuvant and Adjuvant Tiragolumab Plus Atezolizumab, With or Without Platinum-Based Chemotherapy, in Patients With Previously Untreated Locally Advanced Resectable Stage II, IIIA, or Select IIIB Non-Small Cell Lung Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 23, 2021 (Actual)
Primary Completion Date
April 30, 2028 (Anticipated)
Study Completion Date
April 30, 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer (NSCLC)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort A (PD-L1 High)
Arm Type
Experimental
Arm Description
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)
cisplatin/carboplatin + gemcitabine (for squamous only)
carboplatin + paclitaxel
Arm Title
Cohort B (PD-L1 All Comers)
Arm Type
Experimental
Arm Description
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)
cisplatin/carboplatin + gemcitabine (for squamous only)
carboplatin + paclitaxel
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Other Intervention Name(s)
Tecentriq
Intervention Description
Atezolizumab 1200 mg will be administered by intravenous (IV) infusion on Day 1 of each 21-day cycle.
Intervention Type
Drug
Intervention Name(s)
Tiragolumab
Other Intervention Name(s)
MTIG7192A
Intervention Description
Tiragolumab 600 mg will be administered by IV infusion on Day 1 of each 21-day cycle.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
Carboplatin at initial target area under the concentration curve (AUC) of 5 or 6 mg/mL/min will be administered by IV infusion on Day 1 of each 21-day cycle.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Cisplatin at 75 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.
Intervention Type
Drug
Intervention Name(s)
Pemetrexed
Intervention Description
Pemetrexed at 500 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
Gemcitabine at 1000 or 1250 mg/m^2 will be administered by IV infusion on Days 1 and 8 of each 21-day cycle.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
Paclitaxel at 175 or 200 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.
Primary Outcome Measure Information:
Title
Number of Participants With Surgical Delays
Time Frame
Up to approximately 6 years
Title
Number of Participants With Operative and Post-operative Complications
Time Frame
Up to approximately 6 years
Title
Number of Participants With Surgical Cancellations Related to Study Treatment
Time Frame
Up to approximately 6 years
Title
Percentage of Participants With Adverse Events
Time Frame
Up to approximately 6 years
Title
Percentage of Participants Who Achieve Major Pathological Response (MPR)
Time Frame
At the time of surgery (approximately Weeks 17-20)
Secondary Outcome Measure Information:
Title
Percentage of Participants With Pathological Complete Response (pCR)
Time Frame
At the time of surgery (approximately Weeks 17-20)
Title
Event Free Survival (EFS)
Time Frame
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)
Title
Serum Concentrations of Atezolizumab
Time Frame
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)
Title
Serum Concentrations of Tiragolumab
Time Frame
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)
Title
Percentage of Participants With Anti-drug Antibodies (ADAs) to Atezolizumab
Time Frame
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)
Title
Percentage of Participants With ADAs to Tiragolumab
Time Frame
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key inclusion criteria:
Histologically or cytologically confirmed Stage II, IIIA, or select IIIB (T3N2 only) NSCLC of squamous or non-squamous histology
Eligible for R0 resection with curative intent at the time of screening
Adequate pulmonary function to be eligible for surgical resection with curative intent
Eligible to receive a platinum-based chemotherapy regimen
Measurable disease, as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Availability of a representative tumor specimen that is suitable for determination of PD-L1 status
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Normal life expectancy, excluding lung cancer mortality risk
Adequate hematologic and end-organ function
Negative human immunodeficiency virus (HIV) test at screening
Negative serology for active hepatitis B virus (HBV) and active hepatitis C virus (HCV) at screening
Key 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope Cancer Center; Division of Medical Oncology & Experimental Therapeutics
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
City of Hope at Irvine Lennar
City
Irvine
State/Province
California
ZIP/Postal Code
92618
Country
United States
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
USC Norris Cancer Center; Oncology/Hematology - Newport Beach Treatment Center
City
Newport Beach
State/Province
California
ZIP/Postal Code
92663
Country
United States
Facility Name
Georgetown U; Lombardi Comp Can
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20016-1468
Country
United States
Facility Name
University of Kansas Cancer Center
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
Washington University School of Medicine; Medical Oncology
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Winthrop Univ Hospital
City
Mineola
State/Province
New York
ZIP/Postal Code
11501
Country
United States
Facility Name
NYU Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032-3725
Country
United States
Facility Name
Mays Cancer Center
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Sunshine Coast University Hospital; The Adem Crosby Centre
City
Birtinya
State/Province
Queensland
ZIP/Postal Code
4575
Country
Australia
Facility Name
Cabrini Hospital Malvern
City
Malvern
State/Province
Victoria
ZIP/Postal Code
3144
Country
Australia
Facility Name
PETER MACCALLUM CANCER INSTITUTE; MEDICAL ONCOLOGY; Parkville Cancer Clinical Trials Unit
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Facility Name
Kosin University Gospel Hospital
City
Busan
ZIP/Postal Code
49267
Country
Korea, Republic of
Facility Name
St. Vincent's Hospital
City
Gyeonggi-do
ZIP/Postal Code
16247
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Severance Hospital, Yonsei University Health System
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
ICO L'Hospitalet; Servicio de oncologia medica
City
L'Hospitalet de Llobregat
State/Province
Barcelona
ZIP/Postal Code
08908
Country
Spain
Facility Name
Corporacio Sanitaria Parc Tauli; Servicio de Oncologia
City
Sabadell
State/Province
Barcelona
ZIP/Postal Code
8208
Country
Spain
Facility Name
Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Oncologia
City
A Coruña
State/Province
LA Coruña
ZIP/Postal Code
15006
Country
Spain
Facility Name
Hospital Universitario Puerta de Hierro; Servicio de Oncologia
City
Majadahonda
State/Province
Madrid
ZIP/Postal Code
28222
Country
Spain
Facility Name
Vall d?Hebron Institute of Oncology (VHIO), Barcelona
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre; Servicio de Oncologia
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Kantonsspital Baden; Medizinische Klinik, Onkologie
City
Baden
ZIP/Postal Code
5404
Country
Switzerland
Facility Name
Universitaetsspital Basel; Onkologie
City
Basel
ZIP/Postal Code
4031
Country
Switzerland
Facility Name
Kantonsspital Graubünden Medizin Onkologie; Onkologie und Hämatologie
City
Chur
ZIP/Postal Code
7000
Country
Switzerland
Facility Name
Kantonsspital St. Gallen; Onkologie/Hämatologie
City
St. Gallen
ZIP/Postal Code
9007
Country
Switzerland
Facility Name
Kantonsspital Winterthur; Medizinische Onkologie
City
Winterthur
ZIP/Postal Code
8401
Country
Switzerland
Facility Name
UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie
City
Zürich
ZIP/Postal Code
8091
Country
Switzerland
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
Learn more about this trial
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
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