Targeting PD-L1 and TIGIT in Tumors With Tertiary Lymphoid Structures

NCT06713798 | Withdrawn Phase 2 DMC

• 2 other identifiers: 2023-503218-56-002022/3418
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 5

Brief Summary

This study encompasses multicenter open-label, phase II trials. Patients will be dispatched into 2 cohorts:

• Cohort A: Patients naïve from systemic treatment will be randomized according to two treatment modalities: atezolizumab + tiragolumab (arm A1) versus atezolizumab monotherapy (arm A2). 43 patients are to be included in each arm.
• Cohort B: Patients with previous exposure to ICI will be treated with the combination of atezolizumab and tiragolumab. 29 patients are to be included in this cohort.

Conditions

Metastatic Cancer Lung; Advanced Lung Cancer; CBNPC Cancer

Outcome Measures

Primary Outcomes (1)

• Best overall response (BOR) rate

  Best overall response (BOR) rate defined as the proportion of subjects with a partial response (PR) or complete response (CR) within 6 months of treatment initiation, based on RECIST v1.1 criteria, using blinded central review.

  after 6 months of treatment initiation

Study Arms (3)

A1 : the patients naïve from systemic treatment - atezolizumab + tiragolumab

EXPERIMENTAL

Drug: Atezolizumab 1200 mg IV; Drug: Tiragolumab 600 mg IV

A2 : the patients naïve from systemic treatment - atezolizumab

EXPERIMENTAL

Drug: Atezolizumab 1200 mg IV

B: patients with previous exposure to ICI - atezolizumab + tiragolumab

EXPERIMENTAL

Drug: Atezolizumab 1200 mg IV; Drug: Tiragolumab 600 mg IV

Interventions

Tiragolumab 600 mg IV DRUG

Tiragolumab (intravenous 600mg Q3W)

A1 : the patients naïve from systemic treatment - atezolizumab + tiragolumab; B: patients with previous exposure to ICI - atezolizumab + tiragolumab

Atezolizumab 1200 mg IV DRUG

atezolizumab (intravenous 1200mg Q3W)

A1 : the patients naïve from systemic treatment - atezolizumab + tiragolumab; A2 : the patients naïve from systemic treatment - atezolizumab; B: patients with previous exposure to ICI - atezolizumab + tiragolumab

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed TLS-positive advanced or metastatic NSCLC.
• NSCLC systemic treatment naïve or previously treated with chemotherapy and PD1/PDL1 antagonist.
• Cohort A: For patients with TLS-positive NSCLC naïve from systemic treatment with the following requirements:
• PD-L1 Tumor proportion score \< 50%
• No previous systemic treatment for advanced/metastatic disease,
• Cohort B: Patients who received prior anti-PD-1/L1 therapy must fulfill the following requirements:
• Have achieved a complete response, partial response or stable disease (at least for 16 weeks) and subsequently had disease progression while still on anti-PD-1/L1 therapy
• Have received at least two doses of an approved anti-PD-1/L1 therapy (by any regulatory authority)
• Have demonstrated disease progression as defined by RECIST v1.1 within 18 weeks from the last dose of the anti- PD-1/L1 therapy.
• For TLS status: available archived FFPE (Formalin-Fixed Paraffin-Embedded) tumor tissue sample or tumor material newly obtained by biopsy. Except if TLS analysis has already been performed by Biopathological platform at Gustave Roussy (Villejuif, France) or at Bergonié Institute (Bordeaux, France), presence or absence of TLS should be confirmed by central review at Gustave Roussy based on FFPE (Formalin-Fixed Paraffin-Embedded) tumor tissue sample (archived or newly obtained by biopsy for research purpose),
• Age ≥ 18 years,
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1,
• Life expectancy \> 3 months from the signed consent,
• Patient must comply with the collection of tumor biopsies and biomarkers study. Tumors must be accessible for biopsy,
• Adequate hematological, renal, metabolic and hepatic function obtained within 28 days prior to the first study treatment:

You may not qualify if:

• Prior treatment with CD137 agonists or investigational immune checkpoint blockade therapies, including anti-TIGIT, anti-LAG3, etc.
• Known central nervous system malignancy (CNS),
• History of leptomeningeal disease,
• Participation to a study involving a medical or therapeutic intervention in the last 30 days,
• Previous enrollment in the present study,
• Patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons,
• Known hypersensitivity to any involved study drug or any of its formulation components,
• Any history of anaphylaxis, or recent, within 5 months, history of uncontrollable asthma,
• Individuals deprived of liberty or placed under legal guardianship,
• Uncontrolled or symptomatic hypercalcemia (ionized calcium 1.5 mmol/L, calcium 12 mg/dL, or corrected calcium greater than ULN),
• Patients who have experienced Exfoliative dermatitis of any grade, such as Stevens-Johnson Syndrome, toxic epidermal necrolysis, or drug reaction with eosinophilia and systemic symptoms (DRESS syndrome),
• Patients who have experienced myocarditis of any grade,
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (QTcF) ≥ 470 msec, obtained from three consecutive EKGs,
• Any clinically important abnormalities in rhythm, conduction or morphology of resting EKG,

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead
• Roche Global Development: collaborator

MeSH Terms

Conditions

Lung Neoplasms

Interventions

atezolizumab; Tiragolumab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

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

Study Record Dates

• First Submitted: November 27, 2024
• First Posted: December 3, 2024
• Study Start: January 30, 2025
• Primary Completion: September 15, 2025
• Study Completion: September 15, 2025
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5)