Roche reports fail to meet OS primary endpoint on Phase III study SKYSCRAPER-01 evaluating tiragolumab combined with Tecentriq® (atezolizumab) for patients with PD-L1-high, locally advanced or metastatic non-small cell lung (NSCLC)

Roche announced that P3 SKYSCRAPER-01 evaluating tiragolumab (TIGIT) + atezolizumab (PD-L1) vs atezolizumab in 1L PD-L1-high (TPS ≥50%) mNSCLC did not meet the primary End Point of OS at final analysis, ending the regulatory path for this regimen. Roche plans to present data from this study at a medical meeting in 2025.

Key Takeaways

• The failure of SKY-01 removes a key competitor in 1L PD-L1-high mNSCLC although the landscape remains highly crowded and competitive
  • SKY-01 was the only key potential chemo-free regimen ahead of EVOKE-03 in timing; however, ongoing trials of additional TIGIT + PD-1 combinations, TROP2 ADC-based regimens, and other novel MOAs (e.g., PD-1/VEGF bsAb) present key threats in the 1L setting
  • While there are several differences between the two trials, removal of SKY-01 from the 1L NSCLC competitive landscape also removes a potential competitor to STAR-121
    
    • SKY-01 previously failed to meet the co-primary endpoint of PFS but leaked second OS interim analysis data showed a modest positive trend in favor of tira + atezo (HR 0.81; not statistically significant)
    • However, detrimental efficacy was seen in P2/3 SKYSCRAPER-06 of tira + atezo + chemo vs pembro + chemo in 1L non-squamous NSCLC (PFS HR 1.27, OS HR 1.33 at first IA)
• SKY-01 results represent another setback for the anti-TIGIT class as a whole but data from other TIGIT/PD-1 trials, expected 2024-2026, will continue to inform the therapeutic potential of these regimens in 1L NSCLC
  • SKYSCRAPER-03 is now the final ongoing P3 trial of tira in NSCLC (tira + atezo maintenance post-CRT in unresectable Stage III NSCLC), with data possible by EOY 2024 (Roche has guided regulatory filing anticipated in 2025)
  • Results from Merck’s P3 KEYVIBE-007 of pembrolizumab/vibostolimab (PD-1/TIGIT) coformulation + chemo vs. pembro + chemo in 1L PD-L1+ (TPS ≥1%) mNSCLC [STAR-121’s highest threat competitor] and P3 KEYVIBE-003 of pembro/vibo vs pembro in 1L PD-L1-high mNSCLC are anticipated in ~2026
  • BeiGene’s P3 AdvanTIG-302 study of tislelizumab (PD-1) + ociperlimab (TIGIT) vs pembro in 1L PD-L1-high mNSCLC may also read out in ~2026