December 2021: “Roche 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.
“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.
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).
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.
CITYSCAPE study forms the basis of an industry-leading development programme across multiple settings and tumour types.
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.
About the CITYSCAPE study
CITYSCAPE is a global phase II, randomised and blinded study evaluating tiragolumab plus Tecentriq® (atezolizumab) compared with Tecentriq alone in 135 patients with first-line PD-L1-positive locally advanced, unresectable or metastatic non-small cell lung cancer.
Patients were randomised 1:1 to receive either tiragolumab plus Tecentriq or placebo plus Tecentriq, until progressive disease or loss of clinical benefit. Co-primary endpoints are overall response rate (ORR) and progression-free survival (PFS).
Secondary endpoints include safety, overall survival (OS) and patient-reported outcomes (PROs).
PRO results were assessed with EORTC QLQ-C30, a questionnaire developed to assess the quality of life of people with cancer, administered at baseline and throughout study treatment.
A summary of the results are as follows:
| ITT | PD-L1 TPS > 50% | PD-L1 TPS 1–49% | ||||
| Placebo plus Tecentriq | Tiragolumab plus Tecentriq | Placebo plus Tecentriq | Tiragolumab plus Tecentriq | Placebo plus Tecentriq | Tiragolumab plus Tecentriq | |
| N | 68 | 67 | 29 | 29 | 39 | 38 |
| ORR, % | 20.6 | 38.8 | 24.1 | 69.0 | 17.9 | 15.8 |
| mDOR, mo (95% CI) | 10.7 (6.0-18.8) | 17.6 (9.1-26.1) | 8.2 (5.6-10.4) | 15.7 (9.1-NE) | 18.8 (15.9-22.8) | 17.8 (8.3-24.2) |
| mPFS, mo (95% CI) | 3.9 (2.7-4.5) | 5.6 (4.2-10.4) | 4.1 (2.1-6.8) | 16.6 (5.5-22.3) | 3.6 (1.4-5.5) | 4.0 (1.6-5.6) |
| HR (95% CI) | 0.62* (0.42-0.91) | 0.29† (0.15-0.53) | 1.07† (0.67-1.71) | |||
| mOS, mo (95% CI) | 14.5 (9.6-20.4) | 23.2 (14.1-31.5) | 12.8 (4.7-24.2) | NE (30.3-NE) | 14.5 (8.3-25.6) | 13.3 (8.0-20.7) |
| HR (95% CI) | 0.69* (0.44-1.07) | 0.23† (0.10-0.53) | 1.16† (0.70-1.94) |
*Stratified; †Unstratified; NE = non-evaluable.
| Placebo plus Tecentriq n=68 | Tiragolumab plus Tecentriq n= 67 | |
| All cause AEs Grade 3-4 Grade 5 | 66 (97.1%) 27 (39.7%) 7 (10.3%) | 66 (98.5%) 35 (52.2%) 3 (4.5%) |
| Treatment-related AEs Grade 3-4 Grade 5 | 48 (70.6%) 17 (25%) 0 | 55 (82.1%) 15 (22.4%) 2 (3%) |
| Immune mediated AEs Grade 3-4 | 32 (47.1%) 11 (16.2%) | 51 (76.1%) 13 (19.4%) |
| AEs leading to withdrawal | 9 (13.2%) | 10 (14.9%) |
About tiragolumab
Tiragolumab is a first-in-class novel immune checkpoint inhibitor with an intact Fc region. Tiragolumab selectively binds to TIGIT, a novel inhibitory immune checkpoint which suppresses the immune response to cancer.
Based on preclinical research, tiragolumab is thought to work as an immune amplifier with other cancer immunotherapies such as Tecentriq.
The TIGIT pathway is distinct but complementary to the PD-L1/PD-1 pathway. Dual blockade with tiragolumab and Tecentriq may help overcome immune suppression and restore the immune response.
About Tecentriq® (atezolizumab)
Tecentriq is a monoclonal antibody designed to bind with a protein called Programmed Death Ligand-1 (PD-L1), which is expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T-cells.
Tecentriq is a cancer immunotherapy that has the potential to be used as a foundational combination partner with other immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers.
The development of Tecentriq and its clinical programme is based on our greater understanding of how the immune system interacts with tumours and how harnessing a person’s immune system combats cancer more effectively.
Tecentriq is approved in the US, EU and countries around the world, either alone or in combination with targeted therapies and/or chemotherapies in various forms of NSCLC, SCLC, certain types of metastatic urothelial cancer, in PD-L1-positive metastatic triple-negative breast cancer and for hepatocellular carcinoma.
In the US, Tecentriq is also approved in combination with Cotellic® (cobimetinib) and Zelboraf® (vemurafenib) for the treatment of people with BRAF V600 mutation-positive advanced melanoma.”
