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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04832854




Registration number
NCT04832854
Ethics application status
Date submitted
2/04/2021
Date registered
6/04/2021
Date last updated
12/04/2024

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2020-002853-11
Secondary ID [2] 0 0
GO42501
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer (NSCLC) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Tiragolumab
Treatment: Drugs - Carboplatin
Treatment: Drugs - Cisplatin
Treatment: Drugs - Pemetrexed
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Paclitaxel

Experimental: Cohort A (PD-L1 High) - Participants with high programmed death-ligand 1 (PD-L1) expression level will be enrolled in Cohort A and receive neoadjuvant atezolizumab plus tiragolumab for 4 cycles, followed by surgical resection and either adjuvant atezolizumab plus tiragolumab for 16 cycles or adjuvant chemotherapy for 4 cycles at the discretion of the investigator.
Chemotherapy may include:
cisplatin/carboplatin + pemetrexed (for non-squamous only)
carboplatin + gemcitabine (for squamous only)
carboplatin + paclitaxel

Experimental: Cohort B (PD-L1 All Comers) - All comers, which are participants with any PD-L1 expression level, will be enrolled in Cohort B and receive neoadjuvant atezolizumab plus tiragolumab plus chemotherapy for 4 cycles, followed by surgical resection and adjuvant atezolizumab plus tiragolumab for 16 cycles.
Chemotherapy may include:
cisplatin/carboplatin + pemetrexed (for non-squamous only)
carboplatin + gemcitabine (for squamous only)
carboplatin + paclitaxel


Treatment: Drugs: Atezolizumab
Atezolizumab 1200 mg will be administered by intravenous (IV) infusion on Day 1 of each 21-day cycle.

Treatment: Drugs: Tiragolumab
Tiragolumab 600 mg will be administered by IV infusion on Day 1 of each 21-day cycle.

Treatment: Drugs: 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.

Treatment: Drugs: Cisplatin
Cisplatin at 75 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.

Treatment: Drugs: Pemetrexed
Pemetrexed at 500 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.

Treatment: Drugs: 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.

Treatment: Drugs: Paclitaxel
Paclitaxel at 175 or 200 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Surgical Delays
Timepoint [1] 0 0
Up to approximately 6 years
Primary outcome [2] 0 0
Number of Participants With Operative and Post-operative Complications
Timepoint [2] 0 0
Up to approximately 6 years
Primary outcome [3] 0 0
Number of Participants With Surgical Cancellations Related to Study Treatment
Timepoint [3] 0 0
Up to approximately 6 years
Primary outcome [4] 0 0
Percentage of Participants With Adverse Events
Timepoint [4] 0 0
Up to approximately 6 years
Primary outcome [5] 0 0
Percentage of Participants Who Achieve Major Pathological Response (MPR)
Timepoint [5] 0 0
At the time of surgery (approximately Weeks 17-20)
Secondary outcome [1] 0 0
Percentage of Participants With Pathological Complete Response (pCR)
Timepoint [1] 0 0
At the time of surgery (approximately Weeks 17-20)
Secondary outcome [2] 0 0
Event Free Survival (EFS)
Timepoint [2] 0 0
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 outcome [3] 0 0
Serum Concentrations of Atezolizumab
Timepoint [3] 0 0
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 outcome [4] 0 0
Serum Concentrations of Tiragolumab
Timepoint [4] 0 0
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 outcome [5] 0 0
Percentage of Participants With Anti-drug Antibodies (ADAs) to Atezolizumab
Timepoint [5] 0 0
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 outcome [6] 0 0
Percentage of Participants With ADAs to Tiragolumab
Timepoint [6] 0 0
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)

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/04/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/04/2028
Actual
Sample size
Target
Accrual to date
Final
50
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Sunshine Coast University Hospital; The Adem Crosby Centre - Birtinya
Recruitment hospital [2] 0 0
Cabrini Hospital Malvern - Malvern
Recruitment hospital [3] 0 0
PETER MACCALLUM CANCER INSTITUTE; MEDICAL ONCOLOGY; Parkville Cancer Clinical Trials Unit - Melbourne
Recruitment postcode(s) [1] 0 0
4575 - Birtinya
Recruitment postcode(s) [2] 0 0
3144 - Malvern
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
Korea, Republic of
State/province [5] 0 0
Gyeonggi-do
Country [6] 0 0
Korea, Republic of
State/province [6] 0 0
Seoul
Country [7] 0 0
Spain
State/province [7] 0 0
Barcelona
Country [8] 0 0
Spain
State/province [8] 0 0
LA Coruña
Country [9] 0 0
Spain
State/province [9] 0 0
Madrid
Country [10] 0 0
Switzerland
State/province [10] 0 0
Baden
Country [11] 0 0
Switzerland
State/province [11] 0 0
Chur
Country [12] 0 0
Switzerland
State/province [12] 0 0
St. Gallen
Country [13] 0 0
Switzerland
State/province [13] 0 0
Winterthur
Country [14] 0 0
Switzerland
State/province [14] 0 0
Zürich

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04832854
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries