In ORIENT-11, 1L SPP significantly improved progression-free survival (PFS) compared with placebo plus pemetrexed-platinum (PPP) in patients (pts) with AMnsqNSCLC. The study met the primary endpoint of PFS at interim analysis (15NOV2019). Updated OS analysis showed OS benefit. Here we report final OS from ORIENT-11 (Clinical Trials.gov: NCT03607539) using a September 15, 2021 data cutoff.
Pts with treatment-naïve locally AMnsqNSCLC without sensitizing epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations were randomly assigned to SPP (n=266) or PPP (n=131). Pts were stratified by PD-L1 expression, platinum-chemotherapy, and sex. Treatment of SPP or PPP continued until progressive disease (PD), unacceptable toxicity, or a maximum of 24 months. Pts in PPP arm could cross over to receive sintilimab monotherapy upon PD. Primary endpoint was PFS (RECIST v1.1) by blinded independent radiographic review committee. Key secondary endpoint was OS. OS was defined as the date of randomization to the date of death due to any cause.
Baseline characteristics have been previously reported (Yang et. al., JTO 2020). At data cutoff, median study follow-up was 30.8 months. Of the 397 pts enrolled, 243 OS events were observed (SPP: 151 [57%]; PPP: 92 [70%]). Of the pts in PPP arm, 47% crossed over to sintilimab monotherapy per protocol. The mOS was 24.2 months in SPP arm and 16.8 months in PPP arm (Hazard Ratio [HR] of 0.65 [95% CI: 0.50, 0.85]). Estimated 2-year OS rates were 50% (SPP) and 32% (PPP). After adjusting for the crossover effect, OS treatment effect was more pronounced with HR 0.52 (95% CI: 0.38, 0.69). OS benefit across all pre-specified subgroups were largely consistent with what is observed in the ITT population. Overall, the degree of variability observed across subgroups were within the range expected for the size of the subgroup and number of subgroup analyses.
In the final OS analysis from ORIENT-11, SPP continued to demonstrate an improved OS compared to PPP as 1L therapy in AMnsqNSCLC without EGFR or ALK genomic tumor aberrations.
Clinical trial identification
Medical writing assistance was provided by Kristi Gruver, an employee of Eli Lilly and Company.
Legal entity responsible for the study
Eli Lilly and Company.
Eli Lilly and Company.
L. Zhang: Financial Interests, Personal, Research Grant: Innovent Biologics, Inc., Eli Lilly, AstraZeneca, Roche, Bristol Myers Squibband HengRui Pharm. V. Stefaniak, Y. Lin: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. S. Wang, W. Zhang, L. Sun: Financial Interests, Personal, Full or part-time Employment: Innovent Biologics, Inc. All other authors have declared no conflicts of interest.