Abstract 1278P
Background
The first interim analysis of the phase 3 INSPIRE study (NCT04632758) (data cutoff: Nov 13, 2022) showed that iruplinalkib significantly improved PFS versus crizotinib in patients (pts) with advanced ALK+ and ALK TKI-naïve NSCLC. Here we present updated survival and safety results after additional follow-up.
Methods
Pts with ALK+, stage IIIB/IV NSCLC naïve to ALK TKI were randomized (1:1) to oral iruplinalkib 180 mg QD (7-day run-in at 60 mg QD) or crizotinib 250 mg BID. The primary endpoint was PFS assessed by Independent Review Committee (IRC) per the RECIST version 1.1. Secondary endpoints included PFS by investigator (INV), OS and safety.
Results
From Sep 4, 2019 to Dec 2, 2020, 292 pts were randomized (iruplinalkib/crizotinib, n=143/149). The data cutoff date of this updated analysis was Oct 25, 2023. Median follow-up for PFS by IRC was 35.02 months for iruplinalkib and 34.96 months for crizotinib. Median PFS by IRC was 36.80 months for iruplinalkib and 14.55 months for crizotinib (HR, 0.311 [98.02% CI, 0.222-0.436]; stratified one-sided log-rank p<0.0001). Other efficacy results are presented in the table. Incidence of ≥ grade 3 treatment-related AEs was 53.1% for iruplinalkib and 51.0% for crizotinib.
Conclusions
These results demonstrated iruplinalkib continued to improve PFS versus crizotinib in pts with advanced ALK+ and ALK TKI-naïve NSCLC. The safety profile was consistent with prior results and no new safety findings was observed. Table: 1278P
Updated survival results of iruplinalkib versus crizotinib
| Iruplinalkib (n=143) | Crizotinib (n=149) | |
| mPFS by INV, mo (95% CI) | 31.11 (23.98-38.60) | 14.75 (11.10-16.56) |
| HR (95% CI) | 0.423 (0.312-0.573) | |
| mPFS in ALK+ pts by IRC, mo (95% CI) | 45.90 (28.32-NE) | 14.55 (11.07-16.53) |
| HR (95% CI) | 0.292 (0.199-0.430) | |
| mPFS in pts with baseline CNS metastases by IRC, mo (95% CI) | 26.25 (18.27-NE) | 11.01 (7.46-14.72) |
| HR (95% CI) | 0.215 (0.103-0.449) | |
| mPFS in pts without baseline CNS metastases by IRC, mo (95% CI) | 45.90 (29.50-NE) | 16.39 (12.88-18.30) |
| HR (95% CI) | 0.330 (0.222-0.489) | |
| 36-mo OS rate (%) (95% CI) | 81.3 (73.8-86.9) | 75.8 (67.8-82.1) |
Note: ALK+ pts were those whose ALK status was confirmed positive by both central laboratory and local hospitals.
Clinical trial identification
NCT04632758.
Editorial acknowledgement
Legal entity responsible for the study
Qilu Pharmaceutical Co., Ltd.
Funding
Qilu Pharmaceutical Co., Ltd.
Disclosure
M. Si, H. Li, L. Li, X. Kang: Other, Personal, Full or part-time Employment: Qilu Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.
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