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

• ClinicalTrials.gov Identifier: NCT04832854
• Recruitment Status: Recruiting
• First Posted: April 6, 2021
• Last Update Posted: May 25, 2023
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: April 2, 2021
• First Posted Date: April 6, 2021
• Last Update Posted Date: May 25, 2023
• Actual Study Start Date: April 23, 2021
• Estimated Primary Completion Date: April 30, 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 2, 2021)

• Number of Participants With Surgical Delays [ Time Frame: Up to approximately 6 years ]
• Number of Participants With Operative and Post-operative Complications [ Time Frame: Up to approximately 6 years ]
• Number of Participants With Surgical Cancellations Related to Study Treatment [ Time Frame: Up to approximately 6 years ]
• Percentage of Participants With Adverse Events [ Time Frame: Up to approximately 6 years ]
• Percentage of Participants Who Achieve Major Pathological Response (MPR) [ Time Frame: At the time of surgery (approximately Weeks 17-20) ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 2, 2021)

• Percentage of Participants With Pathological Complete Response (pCR) [ Time Frame: At the time of surgery (approximately Weeks 17-20) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer (NSCLC)

Intervention

• Drug: Atezolizumab
  Atezolizumab 1200 mg will be administered by intravenous (IV) infusion on Day 1 of each 21-day cycle.
  Other Name: Tecentriq
• Drug: Tiragolumab
  Tiragolumab 600 mg will be administered by IV infusion on Day 1 of each 21-day cycle.
  Other Name: MTIG7192A
• Drug: Carboplatin
  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.
• Drug: Cisplatin
  Cisplatin at 75 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.
• Drug: Pemetrexed
  Pemetrexed at 500 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.
• Drug: Gemcitabine
  Gemcitabine at 1000 or 1250 mg/m^2 will be administered by IV infusion on Days 1 and 8 of each 21-day cycle.
• Drug: Paclitaxel
  Paclitaxel at 175 or 200 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.

Study Arms

• Experimental: Cohort A (PD-L1 High)

  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
  Interventions:

  • Drug: Atezolizumab
  • Drug: Tiragolumab
  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: Pemetrexed
  • Drug: Gemcitabine
  • Drug: Paclitaxel
• Experimental: Cohort B (PD-L1 All Comers)

  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
  Interventions:

  • Drug: Atezolizumab
  • Drug: Tiragolumab
  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: Pemetrexed
  • Drug: Gemcitabine
  • Drug: Paclitaxel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 2, 2021): 82
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 30, 2028
• Estimated Primary Completion Date: April 30, 2028 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Reference Study ID Number: GO42501 https://forpatients.roche.com/; 888-662-6728 (U.S. Only); global-roche-genentech-trials@gene.com

• Listed Location Countries: Australia, Korea, Republic of, Spain, Switzerland, United States
• Removed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT04832854
• Other Study ID Numbers: GO42501; 2020-002853-11 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: May 2023