Genentech...has been made aware of an inadvertent disclosure of the second interim analysis of the Phase III SKYSCRAPER-01 study, evaluating the investigational anti-TIGIT immunotherapy tiragolumab plus Tecentriq® (atezolizumab) versus Tecentriq alone as an initial (first-line) treatment for people with PD-L1-high locally advanced or metastatic non-small cell lung cancer (NSCLC)....The interim results for the primary endpoint of overall survival were not mature at the time of the second interim analysis, with median overall survival estimates of 22.9 months [95% CI: 17.5, NE] in the tiragolumab plus Tecentriq arm, and 16.7 months [95% CI: 14.6, 20.2] in the Tecentriq monotherapy arm, yielding a hazard ratio (HR) of 0.81 [95% CI: 0.63, 1.03].

NON-SUPPORTIVE EVIDENCE: Roche...today announced results from its phase III SKYSCRAPER-01 study, evaluating the investigational anti-TIGIT immunotherapy tiragolumab plus Tecentriq® (atezolizumab) versus Tecentriq alone as an initial (first-line) treatment for people with PD-L1-high locally advanced or metastatic non-small cell lung cancer (NSCLC). The study did not meet its co-primary endpoint of progression-free survival.

Roche today announced that tiragolumab, a novel cancer immunotherapy designed to bind to TIGIT, has been granted Breakthrough Therapy Designation (BTD) by the US Food and Drug Administration (FDA), in combination with Tecentriq (atezolizumab) for the first-line treatment of people with metastatic non-small cell lung cancer (NSCLC) whose tumours have high PD-L1 expression with no EGFR or ALK genomic tumour aberrations.

Primary analysis of the CITYSCAPE study showed that tiragolumab plus atezolizumab produced a statistically significant and clinically meaningful improvement in ORR and prolonged progression-free survival in patients with NSCLC whose tumors showed high PD-L1 expression (≥50% tumor proportion score) relative to placebo plus atezolizumab.

A phase II trial investigating the anti-TIGIT cancer immunotherapy tiragolumab plus Tecentriq (atezolizumab) compared with Tecentriq alone as a first-line treatment for people with PD-L1-positive metastatic non-small cell lung cancer showed that the combination improved progression-free survival....After 2.5 years median follow-up, tiragolumab plus Tecentriq continued to show an improvement in the intention-to-treat population (n=67), driven by the PD-L1-high population (TPS ≥ 50%) (n=29). In the ITT population, the combination improved PFS by 38% (median PFS=5.6 vs. 3.9 months; HR=0.62, 95% CI: 0.42-0.91) and improved overall response rates (38.8% vs. 20.6%) compared with Tecentriq alone.

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….TA continues to provide a clinically meaningful benefit in pts with metastatic NSCLC, driven by the PD-L1+ TPS ≥50% subgroup....Durable response and encouraging OS continue to support evaluating TA in metastatic PD-L1-high NSCLC.

Comparable PFS improvement with tira + atezo relative to atezo monotherapy was seen in PD-L1–high (≥50% TC) subgroups defined by SP263 (PFS HR 0.23, 95% CI: 0.10–0.53) when compared with PD-L1-high subgroups defined by 22C3...PD-L1 expression, assessed by 22C3 or SP263, may be a biomarker for tira + atezo combination therapy in metastatic PD-L1-positive untreated NSCLC.

An exploratory analysis in people with high levels of PD-L1 (TPS ≥50%) showed a clinically meaningful improvement in ORR (55.2% vs 17.2%) and a 67% reduction in the risk of disease worsening or death (median PFS=not reached vs 3.9 months; HR=0.33, 95% CI: 0.15–0.72) with the combination compared with Tecentriq alone.