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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

NCT04832854

Description:

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.

Related Conditions:
  • Non-Squamous Non-Small Cell Lung Carcinoma
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: GO42501
  • SECONDARY ID: 2020-002853-11
  • NCT ID: NCT04832854

Conditions

  • Non-Small Cell Lung Cancer (NSCLC)

Interventions

DrugSynonymsArms
AtezolizumabTecentriqCohort A (PD-L1 High)
TiragolumabMTIG7192ACohort A (PD-L1 High)
CarboplatinCohort A (PD-L1 High)
CisplatinCohort A (PD-L1 High)
PemetrexedCohort A (PD-L1 High)
GemcitabineCohort A (PD-L1 High)
PaclitaxelCohort A (PD-L1 High)

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Cohort A (PD-L1 High)ExperimentalParticipants 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
  • Atezolizumab
  • Tiragolumab
  • Carboplatin
  • Cisplatin
  • Pemetrexed
  • Gemcitabine
  • Paclitaxel
Cohort B (PD-L1 All Comers)ExperimentalAll 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
  • Atezolizumab
  • Tiragolumab
  • Carboplatin
  • Cisplatin
  • Pemetrexed
  • Gemcitabine
  • Paclitaxel

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants With Surgical Delays
Time Frame:Up to approximately 6 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Percentage of Participants With Pathological Complete Response (pCR)
Time Frame:At the time of surgery (approximately Weeks 17-20)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

August 25, 2021