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A Study of the Efficacy and Safety of RO7198457 in Combination With Atezolizumab Versus Atezolizumab Alone Following Adjuvant Platinum-Doublet Chemotherapy in Participants Who Are ctDNA Positive After Surgical Resection of Stage II-III Non-Small Cell Lung Cancer

NCT04267237

Description:

This study will evaluate the efficacy, safety, pharmacokinetics, immunogenicity and biomarkers of RO7198457 plus atezolizumab compared with atezolizumab alone in patients with Stage II-III non-small cell lung cancer (NSCLC) who are circulating tumor DNA (ctDNA) positive following surgical resection and have received standard-of-care adjuvant platinum-doublet chemotherapy.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of the Efficacy and Safety of RO7198457 in Combination With Atezolizumab Versus Atezolizumab Alone Following Adjuvant Platinum-Doublet Chemotherapy in Participants Who Are ctDNA Positive After Surgical Resection of Stage II-III Non-Small Cell Lung Cancer
  • Official Title: A Phase II, Open-label, Multicenter, Randomized Study of the Efficacy and Safety of RO7198457 in Combination With Atezolizumab Versus Atezolizumab Alone Following Adjuvant Platinum-doublet Chemotherapy in Patients Who Are ctDNA Positive After Surgical Resection of Stage II-III Non-small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: GO41836
  • SECONDARY ID: 2019-003449-14
  • NCT ID: NCT04267237

Conditions

  • Non-small Cell Lung Cancer (NSCLC)

Interventions

DrugSynonymsArms
AtezolizumabTecentriqAtezolizumab
RO7198457Atezolizumab + RO7198457

Purpose

This study will evaluate the efficacy, safety, pharmacokinetics, immunogenicity and biomarkers of RO7198457 plus atezolizumab compared with atezolizumab alone in patients with Stage II-III non-small cell lung cancer (NSCLC) who are circulating tumor DNA (ctDNA) positive following surgical resection and have received standard-of-care adjuvant platinum-doublet chemotherapy.

Trial Arms

NameTypeDescriptionInterventions
AtezolizumabExperimentalParticipants will receive atezolizumab on Day 1 of each 28-day cycle (Q4W) for 12 cycles.
  • Atezolizumab
Atezolizumab + RO7198457ExperimentalParticipants will receive atezolizumab Q4W along with RO7198457 for 12 cycles.
  • Atezolizumab
  • RO7198457

Eligibility Criteria

        Inclusion Criteria:

          -  Age >= 18 years;

          -  Resected Stage II-III Non-small Cell Lung Cancer (NSCLC) per American Joint Committee
             on Cancer staging criteria, 8th revised edition;

          -  Complete R0 resection of Stage II or III NSCLC prior to enrollment and adequate
             recovery from surgery;

          -  Pathological evaluation of mediastinal lymph nodes preoperatively or intraoperatively;

          -  ctDNA (circulating tumor DNA) identified in plasma after resection of Stage II-III
             NSCLC and prior to start of adjuvant platinum-doublet therapy, as determined by
             central testing;

          -  Treatment with at least two cycles of adjuvant platinum-doublet chemotherapy regimens
             for resected NSCLC;

          -  No unequivocal evidence of disease after surgery and adjuvant platinum-doublet
             chemotherapy, as assessed on imaging (computed tomography [CT] scan or magnetic
             resonance imaging [MRI]) within 28 days prior to randomization;

          -  Availability of adequate tumor material;

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1;

          -  Adequate hematologic and end-organ function;

          -  Negative HIV test at screening;

          -  Negative hepatitis B test at screening;

          -  Negative hepatitis C test at screening.

        Exclusion Criteria:

          -  Participants with a known mutation in exons 18-21 of epidermal growth factor receptor
             (EGFR) or with a known anaplastic lymphoma kinase (ALK) or reactive oxygen species
             (ROS) alteration;

          -  History of malignancy other than disease under study within 5 years prior to
             enrollment, with the exception of malignancies with a negligible risk of metastasis or
             death, such as adequately treated carcinoma in situ of the cervix, non-melanoma skin
             cancer, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine
             cancer;

          -  Induction and neoadjuvant systemic therapy prior to resection of NSCLC;

          -  Radiotherapy prior to or after resection of NSCLC;

          -  Prior systemic investigational therapy;

          -  Prior anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, or a cancer
             vaccine;

          -  Treatment with systemic immunostimulatory agents within 6 weeks or 5 drug elimination
             half-lives, 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;

          -  Treatment with monoamine oxidase inhibitors (MAOIs) within 3 weeks prior to initiation
             of study treatment or requirement for ongoing treatment with MAOIs;

          -  Active or history of autoimmune disease or immune deficiency;

          -  Known primary immunodeficiencies, either cellular or combined T-cell and B-cell
             immunodeficiencies;

          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
             pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening
             chest CT scan;

          -  Significant cardiovascular disease;

          -  Major surgical procedure, other than for diagnosis or for resection of disease under
             current study, within 4 weeks prior to initiation of study treatment, or anticipation
             of need for a major surgical procedure during the study;

          -  Known active or latent tuberculosis infection;

          -  Recent acute infection;

          -  Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study
             treatment, or anticipation of need for such a vaccine during study treatment or within
             5 months after the final dose of study treatment;

          -  Prior allogeneic stem cell or solid organ transplantation;

          -  Any other disease, metabolic dysfunction, physical examination finding, or clinical
             laboratory finding that contraindicates the use of an investigational drug, may affect
             the interpretation of the results, or may render the participants at high risk from
             treatment complications;

          -  Known clinically significant liver disease;

          -  Previous splenectomy;

          -  History of severe allergic anaphylactic reactions to chimeric or humanized antibodies
             or fusion proteins;

          -  Known hypersensitivity to Chinese hamster ovary cell products or any component of the
             atezolizumab formulation;

          -  Known allergy or hypersensitivity to any component of RO7198457;

          -  Pregnant or lactating women.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease-free Survival (DFS)
Time Frame:Up to 62 months
Safety Issue:
Description:DFS as assessed by the investigator, is defined as the time from randomization to the date of first documented recurrence of NSCLC or occurrence of new primary NSCLC or death due to any cause, whichever occurs first.

Secondary Outcome Measures

Measure:Percentage of Participants with Adverse Events (AEs) and Serious AEs (SAEs) determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
Time Frame:Up to 90 days after the final dose of study drug or until initiation of another systemic anti-cancer therapy (up to approximately 62 months)
Safety Issue:
Description:
Measure:Plasma Concentrations of RNA at Specified Timepoints
Time Frame:Arm B: Days 1, 8, 15, 22 of Cycle 1 (each cycle is 28 days), Day 1 of Cycle 2, 3, 5, 7, 9, 11 and treatment discontinuation (TD) visit (up to 12 months)
Safety Issue:
Description:
Measure:Plasma Concentrations of (R)-N,N,N-trimethyl-2,3-dioleyloxy-1-propanaminium chloride (DOTMA) at Specified Timepoints
Time Frame:Arm B: Days 1, 8, 15, 22 of Cycle 1 (each cycle is 28 days), Day 1 of Cycle 2, 3, 5, 7, 9, 11 and treatment discontinuation (TD) visit (up to 12 months)
Safety Issue:
Description:
Measure:Maximum Serum Concentration (Cmax) of Atezolizumab at Specified Timepoints
Time Frame:Arm A and Arm B: Day 1 of Cycles 1-4 (each cycle is 28 days) and at TD visit (up to 12 months)
Safety Issue:
Description:
Measure:Minimum Serum Concentration (Cmin) of Atezolizumab at Specified Timepoints
Time Frame:Arm A and Arm B: Day 1 of Cycles 1-4 (each cycle is 28 days) and at TD visit (up to 12 months)
Safety Issue:
Description:
Measure:Change from Baseline in Number of Participants With Anti-drug Antibodies (ADA) to Atezolizumab
Time Frame:Arm A and Arm B: Baseline, Day 1 of Cycles 1-4 (each cycle is 28 days) and at TD visit (up to 12 months)
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hoffmann-La Roche

Trial Keywords

  • Cancer vaccine
  • Neoantigen
  • Personalized
  • Atezolizumab
  • Vaccine
  • Immunotherapy
  • Anti-PDL1
  • Checkpoint Inhibitor
  • Personalized vaccine
  • Non-small cell lung cancer
  • NSCLC
  • Adjuvant

Last Updated

February 11, 2020