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

Non-Small Cell Lung Cancer (NSCLC) Clinical Trial

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04832854
• Other study ID #: GO42501
• Secondary ID: 2020-002853-11
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 23, 2021
• Est. completion date: April 30, 2028

Study information

• Verified date: April 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: April 30, 2028
• Est. primary completion date: April 30, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Atezolizumab
Atezolizumab 1200 mg will be administered by intravenous (IV) infusion on Day 1 of each 21-day cycle.
• Tiragolumab
Tiragolumab 600 mg will be administered by IV infusion on Day 1 of each 21-day cycle.
• Carboplatin
Carboplatin at initial target area under the concentration curve (AUC) of 5 or 6 mg/mL/min will be administered by IV infusion on Day 1 of each 21-day cycle.
• Cisplatin
Cisplatin at 75 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.
• Pemetrexed
Pemetrexed at 500 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.
• Gemcitabine
Gemcitabine at 1000 or 1250 mg/m^2 will be administered by IV infusion on Days 1 and 8 of each 21-day cycle.
• Paclitaxel
Paclitaxel at 175 or 200 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.

Locations

Country	Name	City	State
Australia	Sunshine Coast University Hospital; The Adem Crosby Centre	Birtinya	Queensland
Australia	Cabrini Hospital Malvern	Malvern	Victoria
Australia	PETER MACCALLUM CANCER INSTITUTE; MEDICAL ONCOLOGY; Parkville Cancer Clinical Trials Unit	Melbourne	Victoria
Korea, Republic of	St. Vincent's Hospital	Gyeonggi-do
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Spain	Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Oncologia	A Coruña	LA Coruña
Spain	Vall d?Hebron Institute of Oncology (VHIO), Barcelona	Barcelona
Spain	ICO L'Hospitalet; Servicio de oncologia medica	L'Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Hospital Universitario Puerta de Hierro; Servicio de Oncologia	Majadahonda	Madrid
Spain	Corporacio Sanitaria Parc Tauli; Servicio de Oncologia	Sabadell	Barcelona
Switzerland	Kantonsspital Baden; Medizinische Klinik, Onkologie	Baden
Switzerland	Kantonsspital Graubünden Medizin Onkologie; Onkologie und Hämatologie	Chur
Switzerland	Kantonsspital St. Gallen; Onkologie/Hämatologie	St. Gallen
Switzerland	Kantonsspital Winterthur; Medizinische Onkologie	Winterthur
Switzerland	UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie	Zürich
United States	City of Hope Cancer Center; Division of Medical Oncology & Experimental Therapeutics	Duarte	California
United States	City of Hope at Irvine Lennar	Irvine	California
United States	University of Southern California	Los Angeles	California
United States	Winthrop Univ Hospital	Mineola	New York
United States	Columbia University	New York	New York
United States	NYU Cancer Center	New York	New York
United States	Washington University School of Medicine; Medical Oncology	Saint Louis	Missouri
United States	Georgetown U; Lombardi Comp Can	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Korea, Republic of,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Surgical Delays		Up to approximately 6 years
Primary	Number of Participants With Operative and Post-operative Complications		Up to approximately 6 years
Primary	Number of Participants With Surgical Cancellations Related to Study Treatment		Up to approximately 6 years
Primary	Percentage of Participants With Adverse Events		Up to approximately 6 years
Primary	Percentage of Participants Who Achieve Major Pathological Response (MPR)		At the time of surgery (approximately Weeks 17-20)
Secondary	Percentage of Participants With Pathological Complete Response (pCR)		At the time of surgery (approximately Weeks 17-20)
Secondary	Event Free Survival (EFS)		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)
Secondary	Serum Concentrations of Atezolizumab		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)
Secondary	Serum Concentrations of Tiragolumab		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)
Secondary	Percentage of Participants With Anti-drug Antibodies (ADAs) to Atezolizumab		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)
Secondary	Percentage of Participants With ADAs to Tiragolumab		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)