New data from the phase II CITYSCAPE trial show encouraging results with Roche’s novel anti-TIGIT tiragolumab plus Tecentriq

• After 2.5 years median follow-up, pre-planned exploratory analyses in the PD-L1-high population show clinically meaningful results, with overall survival not yet reached and continued progression-free survival improvement for the combination compared with Tecentriq alone
• CITYSCAPE is the first randomised phase II trial of an anti-TIGIT therapy and is investigating tiragolumab in PD-L1-positive metastatic non-small cell lung cancer
• Tiragolumab is the first anti-TIGIT therapy to be granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration
• CITYSCAPE forms the basis of a broad tiragolumab development programme across multiple settings and tumour types

Basel, 10 December 2021 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced new follow-up efficacy, safety and patient-reported outcomes (PROs) data from the phase II CITYSCAPE trial, investigating the novel anti-TIGIT cancer immunotherapy tiragolumab plus Tecentriq® (atezolizumab) compared with Tecentriq alone as an initial (first-line) treatment for people with PD-L1-positive metastatic non-small cell lung cancer (NSCLC). The full results are being featured as an oral presentation in the Proffered Paper session 2 (Abstract LBA2) at the European Society for Medical Oncology (ESMO) Immuno-Oncology Congress 2021, taking place 8-11 December.¹

“These encouraging results suggest that combining anti-TIGIT and anti-PD-L1 cancer immunotherapies such as tiragolumab and Tecentriq could potentially represent a novel approach to address unmet needs in cancer,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “With tiragolumab, we have the largest and most advanced anti-TIGIT clinical programme, and we look forward to the results of our phase III trials in lung cancer and other challenging tumour types.”

After 2.5 years median follow-up, tiragolumab plus Tecentriq continued to show an improvement in the intention-to-treat (ITT) population (n=67), driven by the PD-L1-high population (TPS ≥ 50%) (n=29). In the ITT population, the combination reduced the risk of disease worsening or death (progression-free survival; PFS) by 38% (median PFS=5.6 vs. 3.9 months; hazard ratio (HR)=0.62, 95% CI: 0.42-0.91) and improved overall response rates (ORR) (38.8% vs. 20.6%) compared with Tecentriq alone. A predefined exploratory analysis in the PD-L1-high population showed a 71% reduction in the risk of disease worsening or death (median PFS=16.6 vs. 4.1 months; HR=0.29, 95% CI: 0.15-0.53) and a clinically meaningful improvement in ORR (69% vs. 24.1%) with the combination compared with Tecentriq alone.¹

The analysis also showed that tiragolumab plus Tecentriq improved overall survival (OS), a secondary endpoint of the study, in the ITT population, which was driven by the PD-L1-high population. After 2.5 years median follow-up, median OS was 23.2 vs. 14.5 months (HR=0.69, 95% CI: 0.44-1.07) in the ITT population. The exploratory data in the PD-L1-high population showed a clinically meaningful OS improvement. The median was not reached for the tiragolumab regimen and is projected to be greater than 30.3 months based on the lower confidence interval (NE (30.3-NE) vs. 12.8 months (4.7-24.2); HR=0.23, 95% CI: 0.10-0.53).¹

Data suggest that the combination was generally well-tolerated, showing similar rates of Grade 3-4 treatment-related adverse events (AEs) when adding tiragolumab to Tecentriq compared with Tecentriq alone (22.4% vs. 25%). The most common all cause AEs (rate greater than 5% difference between study groups) seen with the combination were infusion-related reactions, stiffness, dry skin, fatigue and rash. After longer follow-up, no new safety signals were observed with the combination. Patients generally reported minimal-to-moderate symptoms and generally maintained their quality of life compared with the start of treatment. PRO data from this exploratory analysis showed that lung symptoms, such as dyspnoea and pain, did not appear to deteriorate with the addition of tiragolumab to Tecentriq.¹

CITYSCAPE study forms the basis of an industry-leading development programme across multiple settings and tumour types.³

The phase III SKYSCRAPER-01 trial is currently ongoing to confirm these results in the PD-L1-high population, with the goal of bringing this treatment option to patients. Earlier this year, tiragolumab was granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration – representing the first anti-TIGIT therapy to be granted this designation and the 37th BTD for Roche’s portfolio of medicines. Since 2020, Roche has initiated five phase III trials evaluating tiragolumab plus Tecentriq in early and metastatic disease in lung (SKYSCRAPER-01, SKYSCRAPER-02, SKYSCRAPER-03) and oesophageal cancers (SKYSCRAPER-07, SKYSCRAPER-08). Tiragolumab is also being evaluated in other solid tumours as well as in haematological cancers.