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主要靠PD-L1 high群体驱动，1-49%基本没什么卵用，另外2例治疗相关死亡 LBA2 - Updated Analysis and Patient-Reported Outcomes (PROs) from CITYSCAPE: A Randomised, Double-Blind, Phase II Study of the anti-TIGIT Antibody Tiragolumab + Atezolizumab (TA) Versus Placebo + Atezolizumab (PA) as First-Line Treatment For PD-L1+ NSCLC Background TIGIT is a novel immune checkpoint present on activated T cells and NK cells; inhibition of TIGIT may further amplify the inhibition of the PD-L1/PD-1 pathway. CITYSCAPE (NCT03563716) is the first randomised Phase II study of an anti-TIGIT antibody; the combination of TA showed clinically meaningful improvement in ORR and PFS compared with PA in patients (pts) with metastatic PD-L1+ NSCLC. Here we present updated PFS, OS, and PROs. Methods Eligible pts with chemotherapy-naïve PD-L1+ (TPS ≥1% by local or central 22C3 IHC pharmDX assay) locally advanced, unresectable or metastatic NSCLC were randomised 1:1 to receive TA (T 600 mg IV + A 1200 mg IV) or PA (A 1200 mg IV) every 3 weeks until disease progression or loss of clinical benefit. The EORTC QLQ-C30 was administered at baseline and throughout study treatment. Co-primary endpoints: investigator-assessed ORR and PFS. Additional endpoints: DOR, OS, safety, association of tumour PD-L1 expression levels with clinical outcomes and PROs from the ITT population. Results At this updated analysis (16 Aug 2021), median follow-up was 16.3 mo (range 0.2–35.5) in ITT population. TA improved ORR, PFS and OS compared to PA. For PA vs TA, treatment-related AEs (TRAEs) were 70.6% vs 82.1%; Grade 3–4 TRAEs were 25.0% vs 22.4%; AEs leading to discontinuation were 13.2% vs 14.9%. Changes from baseline scores of global health status and functioning scales were maintained and comparable between arms but showed clinically meaningful improvement in dyspnea (-10.6) and pain (-12.1) for pts who remained on TA at Cycle 16. Conclusion（形势大好不是小好，整个形势比以往任何时候都好） TA continues to provide a clinically meaningful benefit in pts with metastatic NSCLC, driven by the PD-L1+ TPS ≥50% subgroup. TA has a manageable safety profile consistent with PD-L1/PD-1 inhibitors. Patients on TA maintained global health status and functioning and showed improvements in dyspnea and pain. Durable response and encouraging OS continue to support evaluating TA in metastatic PD-L1-high NSCLC. Clinical trial identification NCT03563716. 还是官网实在 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. |
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