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Primary analysis of CITYSCAPE study of the anti-TIGIT antibody Tiragolumab plus Atezolizumab versus Atezolizumab as first-line treatment in patients with PD-L1-selected NSCLC


The immunomodulatory receptor TIGIT is a novel inhibitory immune checkpoint present on activated T cells and NK cells in multiple cancers, including non-small-cell lung cancer ( NSCLC ).

In a phase I study, co-inhibition of TIGIT and PD-L1 signaling with Tiragolumab plus Atezolizumab in cancer immunotherapy-naïve PD-L1 positive NSCLC potentially improved overall response rates ( ORR ) compared to historical ORR with PD-L1/PD-1 inhibitors.

CITYSCAPE is a phase II trial conducted to confirm the efficacy and safety of Tiragolumab plus Atezolizumab compared to placebo plus Atezolizumab in 1L ( first line ) NSCLC.

This prospective, randomized, double-blind, placebo-controlled trial enrolled patients with chemotherapy-naïve PD-L1+ ( TPS greater than or equal to 1% by 22C3 IHC pharmDx Dako assay ) locally advanced or metastatic NSCLC with measurable disease, ECOG PS 0-1, and without EGFR or ALK alterations.

Patients were randomized 1:1 to Tiragolumab + Atezolizumab ( Tiragolumab 600 mg IV plus Atezolizumab 1200 mg IV ) or Atezolizumab alone ( placebo plus Atezolizumab 1200 mg IV ) on day 1 of every 3-week cycle.
Stratification factors were PD-L1 status ( TPS greater than or equal to 50% versus TPS 1-49% ), histology, and tobacco history.

Co-primary endpoints were investigator assessed ORR and progression-free survival ( PFS ), and additional endpoints were duration of response ( DOR ), overall survival ( OS ), and safety.
Exploratory endpoints were the effect of PD-L1 status on ORR and PFS.

135 patients were randomized to Atezolizumab alone ( n = 68 ) or Tiragolumab + Atezolizumab ( n = 67 ).

At primary analysis ( 30 Jun 2019 ), Tiragolumab + Atezolizumab improved ORR and median PFS ( mPFS ) compared to Atezolizumab alone, with median follow-up of 5.9 months.

In the safety population ( 68 in Atezolizumab alone, 67 in Tiragolumab + Atezolizumab ), treatment-related adverse effects ( TRAEs ) occurred in 72% ( Atezolizumab alone ) and 80.6% ( Tiragolumab + Atezolizumab ); grade greater than or equal to 3 TRAEs occurred in 19.1% ( Atezolizumab alone ) and 14.9% ( Tiragolumab + Atezolizumab ).

Adverse effects leading to treatment withdrawal occurred in 10.3% ( Atezolizumab ) and 7.5% ( Tiragolumab + Atezolizumab ).

With an additional six months of follow-up since the primary analysis ( 2 Dec 2019, median follow-up of 10.9 months ), improvement in ORR and mPFS was maintained in intention-to-treat ( ITT ) for Tiragolumab + Atezolizumab ( 37.3% [ 25.0, 49.6 ] and 5.6 months [ 4.2, 10.4 ] ) vs Atezolizumab alone ( 20.6% [ 10.2, 30.9 ] and 3.9 months [ 2.7, 4.5 ] ).
The safety profile remained tolerable.

In conclusion, treatment with Tiragolumab + Atezolizumab compared to Atezolizumab alone showed clinically meaningful improvement in ORR and PFS in intention-to-treat.
The safety profile of Tiragolumab + Atezolizumab was similar to Atezolizumab alone. ( Xagena )

Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020

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