Abstract 636P
Background
It has been hypothesised that tira may synergise with atezo + CE to amplify immune response and improve outcomes in pts with ES-SCLC. SKYSCRAPER-02 (NCT04256421), a global study evaluating tira + atezo + CE in pts with ES-SCLC, showed no survival benefit with adding tira to atezo + CE in this population. SKYSCRAPER-02C (NCT04665856) is a phase III study evaluating whether adding tira to atezo + CE improves survival outcomes in Chinese pts with ES-SCLC.
Methods
Eligible pts with untreated ES-SCLC (treated/untreated asymptomatic brain metastases [BM] allowed) were randomised 1:1 to receive induction tira 600 mg IV or placebo (pbo) + atezo 1200 mg IV + CE for 4 21-day cycles followed by maintenance tira or pbo + atezo every 3 weeks until disease progression or loss of clinical benefit. Primary endpoints: overall survival (OS) and progression-free survival (PFS) in pts without history/presence of BM at baseline (primary analysis set [PAS]). Secondary endpoints: OS and PFS in all randomised pts (full analysis set [FAS]); objective response rate (ORR; FAS); duration of response (DOR; FAS); safety.
Results
At data cut-off (31 Aug 2023), 123 pts were randomised (tira + atezo + CE, n=61; pbo + atezo + CE, n=62) including 110 pts without BM; median duration of follow-up was 26.7 months. Baseline characteristics were similar across both arms; median age was 62 years (FAS). In the PAS and FAS, numerical improvements were observed in PFS and OS with tira + atezo + CE vs pbo + atezo + CE (Table). ORR was higher with tira + atezo + CE vs pbo + atezo + CE; median DOR was similar in both arms. Safety was consistent across both study arms and no new safety signals were identified.
Conclusions
Tira + atezo + CE demonstrated a numerical benefit in OS and PFS over atezo + CE in Chinese pts with untreated ES-SCLC; however this study was not powered for hypothesis testing. The combination was well tolerated with no new safety signals Table: 636P
| Efficacy | Tira + atezo + CE (PAS, n=54) | Pbo + atezo + CE (PAS, n=56) | Tira + atezo + CE (FAS, n=61) | Pbo + atezo + CE (FAS, n=62) |
| Median PFS*, months | 5.6 | 5.4 | 5.6 | 5.4 |
| Unstratified HR (95% CI) | 0.65 (0.43, 0.97) | 0.73 (0.49, 1.07) | ||
| Median OS, months | 18.7 | 13.5 | 17.3 | 14.9 |
| Unstratified HR (95% CI) | 0.89 (0.56, 1.40) | 0.98 (0.64, 1.52) | ||
| Tira + atezo + CE (FAS, n=61) | Pbo + atezo + CE (FAS, n=62) | |||
| ORR*, % | 77.0 | 59.7 | ||
| Median DOR*, months | 5.6 | 5.5 | ||
| Safety † | Tira + atezo + CE (n=60) | Pbo + atezo + CE (n=63) | ||
| Grade 3/4 AE, % | 88.3 | 82.5 | ||
| Grade 5 AE, % | 1.7 | 3.2 | ||
| AE leading to treatment discontinuation, % | 5.0 | 3.2 |
AE, adverse event; CI, confidence interval; HR, hazard ratio*By investigator†In the safety population: all randomised pts who received ≥1 dose of study drug
.Clinical trial identification
NCT04665856.
Editorial acknowledgement
This study is sponsored by F. Hoffmann-La Roche Ltd. Third-party medical writing assistance, under the direction of authors, was provided by Rebecca Benatan, BSc, of Ashfield MedComms, an Inizio company, and was funded by F. Hoffmann-La Roche Ltd.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
S. Lu: Financial Interests, Personal, Advisory Role: AstraZeneca, Pfizer, Hutchison MediPharma, ZaiLab, GenomiCare, Novartis, Yuhan Corporation, Menarini, Mirati Therapeutics, Inc., Daiichi Sankyo, Inc., D3 Bio Limited, Simcere, Takeda, Roche; Non-Financial Interests, Personal, Coordinating PI: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Hansoh; Non-Financial Interests, Institutional, Local PI: ZaiLab, Daiichi Sankyo, Inc., D3 Bio Limited, Roche; Non-Financial Interests, Personal, Member of Board of Directors: Innovent Biologics, Inc.; Non-Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Personal, Research Grant: AstraZeneca, Hutchison, BMS, Heng Rui Beigene, Roche, Hansoh; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Roche, Hansoh; Non-Financial Interests, Institutional, Steering Committee Member: AstraZeneca, Novartis. H. Wang: Financial Interests, Personal, Full or part-time Employment: Roche Pharma Product Development China; Financial Interests, Personal, Stocks/Shares: Roche Pharma Product Development China. L. Zhang: Financial Interests, Personal, Full or part-time Employment: Roche Pharma Product Development China. R.D. Meng: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.; Financial Interests, Personal, Stocks/Shares: Genentech, Inc. All other authors have declared no conflicts of interest.