ASTRO-2021-poster-dziadziuszko-SKYSCRAPER-03-a-phase-III-open-label-randomized-study-of-atezolizumab.pdf

poster

1. •TIGIT is a novel inhibitory immune checkpoint present on
activated T cells and NK cells in multiple cancers;
TIGIT expression correlates with PD-1, especially in
tumour-infiltrating T cells
8
•Tiragolumab is a fully human IgG1/kappa anti-TIGIT
monoclonal antibody with an intact Fc region that blocks the
binding of TIGIT to its receptor PVR (Figure 1)
•Targeted inhibition of TIGIT/PVR, by the anti-TIGIT antibody
tiragolumab, may amplify the durability and duration of the
anti-tumour response of anti-PD-L1/PD-1 antibodies such as
atezolizumab, and broaden the patient population who may
benefit
•In the phase II CITYSCAPE study (NCT03563716),
atezolizumab + tiragolumab showed an improved ORR and
PFS and a similar safety profile compared with placebo +
atezolizumab in 1L patients with metastatic PD-L1+ NSCLC,
with a greater magnitude of improvement observed in the
PD-L1 TPS ≥50% subgroup
9
•While the efficacy benefit in CITYSCAPE was primarily driven
by the PD-L1 high (TPS ≥50%) group, prior chemotherapy and
radiotherapy can upregulate PD-L1 expression in the
tumour,
10–12
potentially enabling PD-L1 negative tumours to
derive a benefit as well; therefore, SKYSCRAPER-03 will
enrol an all-comer patient population
Rafal Dziadziuszko
1
, Myung Ju Ahn
2
, Karen Kelly
3
, Sanjay Popat
4
, Heather Wakelee
5
,
Anne-Marie Baird
6
, Isabelle Rooney
7
, Maryam Afshari
7
, Shelley Coleman
7
, Zoe Zhang
7
,
Hiroshi Kiruki
7
, Namrata Patil
7
, XiaohuiWen
7
, Jeffrey Bradley
8
1
Medical University of Gdańsk, Gdańsk, Poland;
2
Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Republic of Korea;
3
UC Davis Medical Center, Sacramento, CA, USA;
4
The Royal Marsden, London, UK;
5
Stanford University Medical Center, Stanford, CA, USA;
6
Trinity College Dublin, Dublin, Ireland;
7
Genentech, Inc., South San Francisco, CA, USA;
8
Emory University School of Medicine, ATL, USA
2867
Current treatment options for unresectable, Stage III NSCLC
Rationale for atezolizumab + tiragolumab in NSCLC
•Current treatment options for patients with locally advanced, unresectable, Stage III NSCLC include
platinum-based concurrent chemoradiation (cCRT); however, the 5-year OS rates are approximately
15 to 30%
1–3
•In 2018, durvalumab was approved for patients with Stage III NSCLC without progressive disease
after cCRT,
4–7
establishing a new standard of care in this setting
•Investigating the potential of immunotherapy combinations may extend the clinical benefit to more
patients with locally advanced, unresectable, Stage III NSCLC
CLINICAL TRIAL DESIGN
Key inclusion criteria Key exclusion criteria
✓Age ≥18 years
×Any history of prior NSCLC and/or any history of prior treatment for
NSCLC (participants must be newly diagnosed with unresectable
Stage III disease)
✓ECOG PS 0–1 ×NSCLC known to have a mutation in the EGFRor ALKgenes
✓Histologically or cytologically documented NSCLC with locally advanced,
unresectable, Stage III NSCLC of either squamous or non-squamous
histology
×Any evidence of Stage IV disease
✓At least two prior cycles of platinum-based chemotherapy administered
concurrently with radiotherapy*, which must be completed within 1 to 42
days prior to randomisation in the study (one cycle of cCRT is defined as
21 or 28 days)
×Any Grade >2 unresolved toxicity from previous CRT
✓The radiotherapy component in the cCRT must have been at a total dose
of radiation of 60 (±10%) Gray (Gy) (54–66 Gy) administered by intensity
modulated radiotherapy (preferred) or 3D-conforming technique
×Treatment with investigational therapy within 28 days prior to study
treatment initiation
✓No progression during or following concurrent platinum-based CRT
×Prior treatment with immune checkpoint blockade therapies,
including anti-CTLA-4, anti-TIGIT, anti-PD-L1, and anti-PD-1
therapeutic antibodies or CD137 agonists
✓Tumour PD-L1 expression status ×Treatment with systemic immunostimulatory agents
ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, the epidermal growth factor receptor; ALK, anaplastic lymphoma kinase; PD-L1, programmed death-ligand 1;
PD-1, programmed cell death protein 1; CTLA-4, cytotoxic T-lymphocyte antigen 4; TIGIT, T-cell immunoglobulin and ITIM domain. *Concurrent chemotherapy must be given per the
NCCN® (2019) and/or the ESMO guidelines
13
ENROLMENT
•SKYSCRAPER-03 (NCT04513925) is a multicentre, phase III,
open-label, randomised study of atezolizumab and tiragolumab
compared with durvalumab in patients with locally advanced,
unresectable, Stage III NSCLC who have not progressed after cCRT.
The study schema for SKYSCRAPER-03 is shown in Figure 2
•Key eligibility criteria for SKYSCRAPER-03 are listed in Table 1
References
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Theauthorswouldliketothanktheparticipants,theirfamiliesandtheparticipatingstudy
centres.TheauthorswouldliketothankEvelynYaofortheircontributionstothis
publication,onbehalfofMaryamAfshari.ThisworkwasfundedbyF.Hoffmann-LaRoche
Ltd.Medicalwritingassistance,underthedirectionoftheauthors,wasprovidedbyDemi
Christofi,MSc,ofAshfieldMedComms,anAshfieldHealthcompany,andfundedby
F.Hoffmann-LaRocheLtd.
ProfessorR.Dziadziuszkoreportsthefollowingpotentialconflictofinterests:Advisoryboard(financial):
F.Hoffmann-LaRocheLtd,Pfizer,BoehringerIngelheim,Bayer,Novartis,AstraZeneca,MerckSharp&
Dohme,SeattleGenetics,FoundationMedicineandTakeda;Principalinvestigator(financial):F.
Hoffmann-LaRocheLtd,MerckSharp&Dohme,Amgen,Janssen,Bristol-MyersSquibband
AstraZeneca;Productsamples(non-financial):F.Hoffmann-LaRocheLtd,NovartisandPfizer
1. Goldstrawet al. J ThoracOncol 2015; 2. Yoon et al. World J Clin Oncol 2017; 3. Bradley et al. Int J RadiatOncol BiolPhys 2017;
4. Gray et al. ASCO 2019; 5. Imfinzi SmPC 2021; 6. Imfinzi PI 2021; 7. Spigelet al. ASCO 2021; 8. Johnson et al. Cancer Cell 2014;
9. Rodriguez-Abreu et al. ASCO 2020; 10. Zhang et al. Mol Immunol 2008; 11. Formenti and Demaria. J Natl Cancer Inst 2013;
12. Rodriguez-Ruiz et al. Trends Immunol 2018; 13. Postmus et al. Ann Oncol 2017
Active T cell
Tumour cell
Active NK cell
TIGIT
PVR
CD226
Anti-TIGIT
Anti-TIGIT
FURTHER INFORMATION ACKNOWLEDGEMENTS DISCLOSURES
SKYSCRAPER-03: Phase III, Open-Label
Randomised Study of Atezolizumab +
Tiragolumab vs Durvalumab in Patients with
Locally Advanced, Unresectable, Stage III
NSCLC Who Have Not Progressed After
Platinum-based Concurrent Chemoradiation
•Argentina
•Australia
•Austria
•Belgium
•Brazil
•Canada
•China
•Czech Republic
•France
•Portugal
•Republic of Korea
•Spain
•Taiwan
•Thailand
•Turkey
•United Kingdom
•United States
•Germany
•Greece
•Hong Kong
•Hungary
•Israel
•Italy
•Japan
•Netherlands
•Poland
Figure 3: Enrolment sites in SKYSCRAPER-03
Treat until progression or unacceptable toxicity
R
1:1
Locally advanced, unresectable, Stage III NSCLC who have
received ≥2 cycles of platinum-based cCRT
without progression
N = ~800
Figure 2: SKYSCRAPER-03 study design
Primary endpoint:
PFS by independent
review facility
assessment per
RECIST v1.1
Safety,
pharmacokinetics,
immunogenicity
and biomarkers will
also be evaluated
Key secondary
endpoints:
OS, investigator-
assessed PFS, ORR,
DOR, PFS and OS rates
at 12, 18 and 24 months
*Durvalumab at Q2W or Q4W based on the investigator in consultation with the patient and/or local standard of care;
†
For patients who weigh ≥30 kg; Q2W, once every 2 weeks; Q4W, once every 4 weeks; IV, intravenous
Table 1: Key eligibility criteria for SKYSCRAPER-03
Figure 1: Anti-TIGIT MoA
•Approximately 800 participants will be recruited into the SKYSCRAPER-03 study at approximately 230 sites globally (Figure 3); enrolment is currently ongoing
PVR, poliovirus receptor; TIGIT, T-cell immunoglobulin and ITIM
domain; NK, natural killer
Tiragolumab 840 mg IV Q4W +
atezolizumab 1680 mg IV Q4W
for 13 cycles (12 months)
Durvalumab* 10 mg/kg IV Q2W
or 1500 mg IV Q4W
†
for 13 cycles (12 months)