Tiragolumab and Atezolizumab in Patients With Non-squamous Non-small Cell Lung Cancer (NSCLC) and Untreated Brain Metastases

NCT05746481 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: HCC 22-045
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial is aimed at the evaluation of the safety and clinical activity of tiragolumab in combination with atezolizumab with or without chemotherapy in the first line treatment of metastatic non-squamous NSCLC patients with asymptomatic untreated brain metastases.

Conditions

Non-small Cell Lung Cancer

Keywords

PD-L1 tumor proportion score (TPS); salvage radiation therapy; brain metastases

Outcome Measures

Primary Outcomes (1)

• Rate of Initiation of Salvage Radiation Therapy to Central Nervous System (CNS)

  The proportion of patients that require salvage radiation therapy to the CNS (within 18 weeks from study initiation). Salvage radiation therapy is radiation treatment given for suspected recurrent malignant disease.

  Up to 18 weeks

Secondary Outcomes (10)

• Adverse Events Related to Treatment

  Up to 12 months

• Brain Metastasis Response Rate (BMRR)

  Up to 24 months

• Response Per RANO Criteria

  Up to 24 months

• Response Per RECIST

  Up to 24 months

• Progression-free Survival (PFS) - Per Patient

  Up to 24 months

Study Arms (1)

Single Treatment Arm

EXPERIMENTAL

Tiragolumab in combination with atezolizumab, pemetrexed, and carboplatin.

Drug: Tiragolumab; Drug: Atezolizumab; Drug: Pemetrexed; Drug: Carboplatin

Interventions

Tiragolumab DRUG

Tiragolumab (an investigational novel immune checkpoint inhibitor): 600 mg IV for induction treatment administered on Day 1 of each 21-day cycle for 4 cycles. Maintenance therapy will continue with tiragolumab on Day 1 of each 21-day cycle.

Also known as: RO7092284

Single Treatment Arm

Atezolizumab DRUG

Atezolizumab (monoclonal antibody): 1200 mg IV administered on Day 1 of each 21-day cycle.

Also known as: Tecentriq, RO5541267

Single Treatment Arm

Pemetrexed DRUG

Pemetrexed (antifolate antineoplastic agent chemotherapy): 500 mg/m2 administered IV on Day 1 of each 21-day cycle.

Also known as: Alimta, Pemfexy

Single Treatment Arm

Carboplatin DRUG

Carboplatin AUC 5 (alkylating agent chemotherapy): injection administered on Day 1 of each 21-day cycle.

Also known as: Paraplatin

Single Treatment Arm

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed non-squamous NSCLC.
• In patients treated with the combination of tiragolumab and atezolizumab, patients must have PDL1 TPS \>50%, as determined by an FDA-approved test.
• Patients must have asymptomatic brain metastases with at least one untreated evaluable (per RANO-BM) brain metastasis of 5 mm or more. A growing lesion previously treated with whole brain radiotherapy is acceptable given the lower incidence of radiation necrosis. Lesions previously treated with SRS may not be used as target lesions.
• o Patients are not required to have measurable disease outside the CNS per RECIST 1.1.
• Prior chemotherapy, immunotherapy or radiation given with curative intent in early stage or locoregionally advanced NSCLC is permitted, if completed more than 12 months prior to initiation of study treatment.
• Prior radiation with palliative intent in the metastatic setting to non-CNS lesions is permitted (no wash-out period).
• Age ≥18 years.
• ECOG performance status ≤ 1.
• Life expectancy ≥12 weeks.
• Patients must have normal organ and marrow function as defined below:
• Absolute neutrophil count ≥1,500/mcL
• Platelets ≥100,000/mcL
• Total bilirubin ≤ institutional upper limit of normal (ULN)
• AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN
• Creatinine Clearance (CrCl) ≥45 mL/min/1.73 m2

You may not qualify if:

• Prior systemic therapy for metastatic disease is not allowed.
• Patients whose tumors harbor oncogenic drivers with an approved 1st line therapy (e.g. EGFR, ALK, and ROS1 alterations) are excluded.
• Patients who are receiving any other investigational agents.
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study.
• Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
• Rash must cover \< 10% of body surface area
• Disease is well controlled at baseline and requires only topical corticosteroids
• No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis or fibrosis in a radiation field is permitted.
• History of leptomeningeal disease.
• Active tuberculosis.
• Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina.
• Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study.

Sponsors & Collaborators

• Genentech, Inc.: collaborator
• Liza Villaruz, MD: lead

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Brain Neoplasms

Interventions

Tiragolumab; atezolizumab; Pemetrexed; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

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; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Barbara Stadterman, MPH, CCRP
• Organization: UPMC Hillman Cancer Center

stadtermanbm@upmc.edu

4126475554

Study Officials

• Liza C Villaruz, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: February 16, 2023
• First Posted: February 27, 2023
• Study Start: August 10, 2023
• Primary Completion: August 19, 2024
• Study Completion: November 8, 2025
• Last Updated: January 22, 2026
• Results First Posted: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)