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
Primary Purpose
Non-small Cell Lung Cancer (NSCLC)
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Atezolizumab
RO7198457
Sponsored by
About this trial
This is an interventional treatment trial for Non-small Cell Lung Cancer (NSCLC) focused on measuring Cancer vaccine, Neoantigen, Personalized, Atezolizumab, Vaccine, Immunotherapy, Anti-PDL1, Checkpoint Inhibitor, Personalized vaccine, Non-small cell lung cancer, NSCLC, Adjuvant
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Atezolizumab
Atezolizumab + RO7198457
Arm Description
Participants will receive atezolizumab on Day 1 of each 28-day cycle (Q4W) for 12 cycles.
Participants will receive atezolizumab Q4W along with RO7198457 for 12 cycles.
Outcomes
Primary Outcome Measures
Disease-free Survival (DFS)
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
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)
Plasma Concentrations of RNA at Specified Timepoints
Plasma Concentrations of (R)-N,N,N-trimethyl-2,3-dioleyloxy-1-propanaminium chloride (DOTMA) at Specified Timepoints
Maximum Serum Concentration (Cmax) of Atezolizumab at Specified Timepoints
Minimum Serum Concentration (Cmin) of Atezolizumab at Specified Timepoints
Change from Baseline in Number of Participants With Anti-drug Antibodies (ADA) to Atezolizumab
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04267237
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Withdrawn
Why Stopped
Accrual timelines
Study Start Date
March 31, 2021 (Anticipated)
Primary Completion Date
September 30, 2025 (Anticipated)
Study Completion Date
September 30, 2025 (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
5. Study Description
Brief Summary
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.
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)
Keywords
Cancer vaccine, Neoantigen, Personalized, Atezolizumab, Vaccine, Immunotherapy, Anti-PDL1, Checkpoint Inhibitor, Personalized vaccine, Non-small cell lung cancer, NSCLC, Adjuvant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Masking Description
Open label
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Atezolizumab
Arm Type
Experimental
Arm Description
Participants will receive atezolizumab on Day 1 of each 28-day cycle (Q4W) for 12 cycles.
Arm Title
Atezolizumab + RO7198457
Arm Type
Experimental
Arm Description
Participants will receive atezolizumab Q4W along with RO7198457 for 12 cycles.
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Other Intervention Name(s)
Tecentriq
Intervention Description
Atezolizumab 1680 mg will be administered by intravenous (IV) infusion on Day 1 of Cycles 1-12.
Intervention Type
Drug
Intervention Name(s)
RO7198457
Intervention Description
RO7198457 will be administered by IV infusion at protocol-defined intervals for 12 cycles.
Primary Outcome Measure Information:
Title
Disease-free Survival (DFS)
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.
Time Frame
Up to 62 months
Secondary Outcome Measure Information:
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
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.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). 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 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
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