Clinical trial NCT04832854: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer (NSCLC)
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2021-04-06
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants With Surgical Delays
timeFrame: Up to approximately 6 years
measure: Number of Participants With Operative and Post-operative Complications
timeFrame: Up to approximately 6 years
measure: Number of Participants With Surgical Cancellations Related to Study Treatment
timeFrame: Up to approximately 6 years
measure: Percentage of Participants With Adverse Events
timeFrame: Up to approximately 6 years
measure: Percentage of Participants Who Achieve Major Pathological Response (MPR)
timeFrame: At the time of surgery (approximately Weeks 17-20)
Secondary outcomes:
measure: Percentage of Participants With Pathological Complete Response (pCR)
timeFrame: At the time of surgery (approximately Weeks 17-20)
measure: Event Free Survival (EFS)
timeFrame: 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)
measure: Serum Concentrations of Atezolizumab
timeFrame: 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)
measure: Serum Concentrations of Tiragolumab
timeFrame: 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)
measure: Percentage of Participants With Anti-drug Antibodies (ADAs) to Atezolizumab
timeFrame: 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)
measure: Percentage of Participants With ADAs to Tiragolumab
timeFrame: 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)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Cancer Center
state: California
city: Irvine
country: United States
facility: City of Hope at Irvine Lennar
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Mineola
country: United States
facility: Winthrop Univ Hospital
state: New York
city: New York
country: United States
facility: NYU Cancer Center
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Birtinya
country: Australia
facility: Sunshine Coast University Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Institute
state: Victoria
city: Gyeonggi-do
country: Korea, Republic of
facility: St. Vincent's Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: L Hospitalet De Llobregat
country: Spain
facility: ICO L'Hospitalet
state: Barcelona
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli
state: Barcelona
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro
state: Madrid
city: Barcelona
country: Spain
facility: Vall d?Hebron Institute of Oncology (VHIO), Barcelona
city: La Coruna
country: Spain
facility: Complejo Hospitalario Universitario A Coruña (CHUAC)
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Chur
country: Switzerland
facility: Kantonsspital Graubünden Medizin Onkologie
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
city: Zürich
country: Switzerland
facility: UniversitätsSpital Zürich
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: