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

Non-small Cell Lung Cancer (NSCLC) Clinical Trial

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Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04267237
• Other study ID #: GO41836
• Secondary ID: 2019-003449-14
• Status: Withdrawn
• Phase: Phase 2
• Start date: March 31, 2021
• Est. completion date: September 30, 2025

Study information

• Verified date: February 2021
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 30, 2025
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer (NSCLC)

Intervention

Drug:
• Atezolizumab
Atezolizumab 1680 mg will be administered by intravenous (IV) infusion on Day 1 of Cycles 1-12.
• RO7198457
RO7198457 will be administered by IV infusion at protocol-defined intervals for 12 cycles.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 62 months
Secondary	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)		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)
Secondary	Plasma Concentrations of RNA at Specified Timepoints		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)
Secondary	Plasma Concentrations of (R)-N,N,N-trimethyl-2,3-dioleyloxy-1-propanaminium chloride (DOTMA) at Specified Timepoints		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)
Secondary	Maximum Serum Concentration (Cmax) of Atezolizumab at Specified Timepoints		Arm A and Arm B: Day 1 of Cycles 1-4 (each cycle is 28 days) and at TD visit (up to 12 months)
Secondary	Minimum Serum Concentration (Cmin) of Atezolizumab at Specified Timepoints		Arm A and Arm B: Day 1 of Cycles 1-4 (each cycle is 28 days) and at TD visit (up to 12 months)
Secondary	Change from Baseline in Number of Participants With Anti-drug Antibodies (ADA) to Atezolizumab		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)