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

NCT04832854 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: GO425012020-002853-11
• Study Type: interventional
• Target: 50
• Locations: 5 countries
• Sites: 21

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.

Conditions

Non-Small Cell Lung Cancer (NSCLC)

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Surgical Delays

  Participants were scheduled to undergo surgical resection of their tumor upon completion of four cycles of neo-adjuvant therapy. Prior to the surgery, the attending surgeon and medical oncologist assessed the participant to check if it was clinically feasible for them to undergo surgery (pre-surgical assessment). Surgery was to be done within 30 days of the pre-surgical assessment visit. Assessment of surgical delays were made by assessing the data entered in the electronic case report forms (eCRFs).

  Up to approximately 4.7 months

• Number of Participants With Operative and Post-operative Complications

  Participants who underwent surgical resection of their tumor and had intraoperative or post-operative complications were reported.

  From day of surgery up to end of safety follow-up (up to approximately 17.5 months)

• Number of Participants With Surgical Cancellations Related to Study Treatment

  Participants were scheduled to undergo surgical resection of their tumor upon completion of four cycles of neo-adjuvant therapy. Prior to the surgery, the attending surgeon and medical oncologist assessed the participant for to check if it was clinically feasible for them to undergo surgery (pre-surgical assessment). Surgery was to be done within 30 days of the pre-surgical assessment visit. Assessment of surgical delays were made by assessing the data entered in the eCRFs.

  Up to approximately 4.7 months

• Number of Participants With Adverse Events (AEs)

  AE=any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any of the following: Any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product; Any new disease or exacerbation of an existing disease; Recurrence of an intermittent medical condition not present at baseline; Any deterioration in a laboratory value or other clinical test that is associated with symptoms or leads to a change in study treatment or concomitant treatment or discontinuation from study treatment; AEs that are related to a protocol-mandated intervention, including those that occur prior to assignment of study treatment.

  From signing of informed consent to up to 90 days after the final dose of study treatment (Up to approximately 1.7 years)

• Major Pathological Response (MPR) Rate

  MPR rate was defined as the percentage of participants who achieved MPR. MPR was defined as ≤10% residual viable tumor at the time of surgical resection in the primary tumor, as assessed by the local pathology laboratory. Patients who did not proceed to surgery were considered as non-responders for MPR. 95% confidence interval (CI) was calculated using the Wilson Score Method. Percentages have been rounded off.

  At the time of surgical resection (From Day 114 to Day 144)

Secondary Outcomes (6)

• Percentage of Participants With Pathological Complete Response (pCR)

  At the time of surgical resection (From Day 114 to Day 144)

• Event-free Survival (EFS)

  Up to approximately 3.8 years

• Serum Concentrations of Atezolizumab at Specified Timepoints

  Prior to the first infusion on Day 1 of Cycles 1, 2, 3, 4, 5, 8, 12, and 16; 30 minutes (min) post-infusion Day 1 of Cycle 1; (Cycle=21 days)

• Serum Concentrations of Tiragolumab at Specified Timepoints

  Prior to the first infusion on Day 1 of Cycles 1, 2, 3, 4, 5, 8, 12, 16; 30 minutes (min) post-infusion Cycle 1 Day 1; (Cycle=21 days)

• Percentage of Participants With Anti-drug Antibodies (ADAs) to Atezolizumab

  Up to approximately 3.8 years

Study Arms (2)

Cohort A (PD-L1 High)

EXPERIMENTAL

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

Drug: Atezolizumab; Drug: Tiragolumab; Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed; Drug: Gemcitabine; Drug: Paclitaxel

Cohort B (PD-L1 All Comers)

EXPERIMENTAL

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

Drug: Atezolizumab; Drug: Tiragolumab; Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed; Drug: Gemcitabine; Drug: Paclitaxel

Interventions

Atezolizumab DRUG

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

Also known as: Tecentriq

Cohort A (PD-L1 High); Cohort B (PD-L1 All Comers)

Tiragolumab DRUG

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

Also known as: MTIG7192A

Cohort A (PD-L1 High); Cohort B (PD-L1 All Comers)

Carboplatin DRUG

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.

Cohort A (PD-L1 High); Cohort B (PD-L1 All Comers)

Cisplatin DRUG

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

Cohort A (PD-L1 High); Cohort B (PD-L1 All Comers)

Pemetrexed DRUG

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

Cohort A (PD-L1 High); Cohort B (PD-L1 All Comers)

Gemcitabine DRUG

Gemcitabine at 1000 or 1250 mg/m\^2 will be administered by IV infusion on Days 1 and 8 of each 21-day cycle.

Cohort A (PD-L1 High); Cohort B (PD-L1 All Comers)

Paclitaxel DRUG

Paclitaxel at 175 or 200 mg/m\^2 will be administered by IV infusion on Day 1 of each 21-day cycle.

Cohort A (PD-L1 High); Cohort B (PD-L1 All Comers)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (21)

City of Hope Cancer Center

Duarte, California, 91010, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Winthrop Univ Hospital

Mineola, New York, 11501, United States

Location

NYU Cancer Center

New York, New York, 10016, United States

Location

Columbia University

New York, New York, 10032-3725, United States

Location

Sunshine Coast University Hospital

Birtinya, Queensland, 4575, Australia

Location

Peter Maccallum Cancer Institute

Melbourne, Victoria, 3000, Australia

Location

St. Vincent's Hospital

Gyeonggi-do, 16247, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

ICO L'Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Corporacio Sanitaria Parc Tauli

Sabadell, Barcelona, 08208, Spain

Location

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, 28222, Spain

Location

Complejo Hospitalario Universitario A Coruña (CHUAC)

A Coruña, 15006, Spain

Location

Vall d?Hebron Institute of Oncology (VHIO), Barcelona

Barcelona, 08035, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Kantonsspital Baden

Baden, 5404, Switzerland

Location

Kantonsspital Graubünden Medizin Onkologie

Chur, 7000, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Kantonsspital Winterthur

Winterthur, 8401, Switzerland

Location

UniversitätsSpital Zürich

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

atezolizumab; Tiragolumab; Carboplatin; Cisplatin; Pemetrexed; Gemcitabine; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2021
• First Posted: April 6, 2021
• Study Start: April 23, 2021
• Primary Completion: March 5, 2025
• Study Completion: March 5, 2025
• Last Updated: March 11, 2026
• Results First Posted: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

AU (2); CH (5); KR (2); ES (6); US (6)