KEY TAKEAWAYS
- SKYSCRAPER-02 (NCT04256421) is a Phase 2 trial to examine if a combination of atezo + CE could be improved by adding tira in patients with ES-SCLC.
- The study primarily aims to evaluate the investigator-assessed PFS and OS in patients with untreated ES-SCLC, with or without BM.
- The study randomly assigns eligible patients to receive induction tira or pbo combined with atezo + CE for 4 x 21-day cycles.
- PAS and FAS were used to compare the efficacy of tira + atezo + CE to pbo + atezo + CE.
- TRAEs occurred in 52.3% (tira + atezo + CE) and 55.7% (pbo + atezo + CE) among patients, and no additional advantage was observed in PFS or OS.
Atezo, in conjunction with etoposide, was the first cancer immunotherapy approved for the 1L treatment of ES-SCLC. Most patients (pts) get more severe symptoms as their disease progresses. TIGIT is a novel inhibitory immune checkpoint found on activated T cells and NK cells.
Tiragolumab (Tira) (anti-TIGIT) may enhance the immune response when combined with other immunotherapies, such as PD-L1/PD-1 inhibitors, leading to better clinical outcomes. SKYSCRAPER-02 (NCT04256421) examines if the antitumor effect and survival advantages of the combination of atezo + CE could be improved by adding tira in pts with ES-SCLC.
Eligible pts with untreated ES-SCLC (asymptomatic treated or untreated brain metastases [BM] permitted) were randomly assigned to receive induction tira 600 mg IV or placebo (pbo) combined with atezo 1,200 mg IV + CE for 4 x 21-day cycles, followed by maintenance tira or placebo combined with atezo every 3 weeks until disease progression or loss of clinical benefit. ECOG PS (0 vs. 1), BM presence/history (yes vs. no), and LDH (upper limit of normal [ULN] vs. >ULN) are stratification criteria.
All randomized pts without a history or presence of BM at baseline were evaluated using investigator-assessed PFS and OS as co-primary objectives (primary analysis set [PAS]). Additional goals include PFS and OS in all randomized pts, irrespective of BM status (full analysis set [FAS]), objective response rate, duration of response, and safety.
About 490 patients (tira + atezo + CE, n=243; pbo + atezo + CE, n=247) were randomly assigned. As of February 6, 2022, the median follow-up time was 13.9 months (mo); the results represent the final analysis for PFS and the interim analysis for OS. Comparing tira + atezo + CE to pbo + atezo + CE in the PAS, no further advantage was observed in PFS or OS. PFS and OS in the FAS were comparable to those in the PAS. TRAEs occurred in 52.3% (tira + atezo + CE) and 55.7% (pbo + atezo + CE) among students in grades 3 and 4, and 0.4% (tira + atezo + CE) and 2.0% (pbo + atezo + CE) among students in grades 5 and 6. With Tira + atezo + CE and pbo + atezo + CE, TRAEs that resulted in any treatment termination occurred in 5.0% and 5.3% of cases, respectively.
Patients with untreated ES-SCLC with or without BM did not benefit from adding tira to atezo + CE compared. Pts found no additional safety signs, and the combination was well tolerated. The investigation will proceed to the planned conclusion of the OS analysis.
Source: https://meetings.asco.org/abstracts-presentations/213673
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT04256421
Rudin C, Liu S, Lu S, Soo R, Hong M, Lee J, Bryl M, Dumoulin D, Rittmeyer A, Chiu C, Ozyilkan O, Navarro A, Novello S, Ozawa Y, Meng R, Hoang T, Lee A, Wen X, Huang M, and Reck M. SKYSCRAPER-02: Primary results of a phase III, randomized, double-blind, placebo-controlled study of atezolizumab (atezo) + carboplatin + etoposide (CE) with or without tiragolumab (tira) in patients (pts) with untreated extensive-stage small cell lung cancer (ES-SCLC). J Clin Oncol 40, 2022 (suppl 17; abstr LBA8507)
