Abstract 649P
Background
Osimertinib plus chemotherapy significantly improved PFS as first-line (1L) treatment in EFGR mutated (EGFRm) advanced NSCLC (FLAURA2). To mitigate the cytotoxicity and inconvenience of chemotherapy, we explored a chemo-free oral combination therapy with osimertinib (osi) plus anlotinib (anlo, an multi-targeted TKI inhibit both tumour angiogenesis and growth) in 1L setting.
Methods
In this prospective, single arm, phase Ib/IIa study, treatment-naïve patients (pts) with EGFRm advanced NSCLC were enrolled. The phase Ib assessed the RP2D and safety of osi plus anlo (Part A: osi, 80mg daily; anlo, 8mg/10mg/12mg daily, D1-14, 21d/cycle). Phase IIa is an expansion cohort at RP2D (Part B). Primary endpoint is ORR. Secondary endpoints include DCR, DoR, PFS, OS and safety.
Results
25 pts were enrolled (Part A: 12, Part B: 13) and treated. Osi plus anlo was well tolerated, and RP2D was osi 80mg and anlo 12mg. Median age was 59 years (range 38 to 77), 11 were female, 24 were ECOG-PS 1, and 11 were 21 L858R, 6 had CNS metastases. At data cut-off (Jun 20, 2024), in 23 response evaluable pts (3 anlo 8mg, 3 anlo 10mg, 17 anlo 12mg), ORR was 65.2% (95%CI 42.7–83.6), DCR was 95.7% (95%CI 78.0–99.9). The median follow-up was 39.2 months, median PFS was 31.5 months (95%CI 17.9–NE) and 3y-OS was 74.3% (95%CI 58.5-94.4). In 17 pts who received anlo 12 mg, ORR was 58.8% (95%CI 32.9-81.6), DCR was 100% (95%CI 80.5-100.0), median PFS was 29.7 months (95%CI 12.1-NE) and 3y-OS was 61.9% (95%CI 41.9-91.4) (Table). Adverse events (AEs) were observed in 24 (96.0%) pts. Grade≥3 AEs and SAEs were experienced by 8 (32.0%) and 4 (16.0%) pts. No unexpected AEs occurred Table: 649P
Efficacy summary
| Efficacy endpoint | osi 80mg+anlo 12mg (N=17) |
| ORR, % (95% CI) | 58.8 (32.9-81.6) |
| DCR, % (95% CI) | 100 (80.5-100.0) |
| Median DoR, months (range) | 29.1 (22.8, NE) |
| Median PFS, months (95% CI) | 29.7 (12.1-NE) |
| 19 deletion | 31.0 (29.0-NE) |
| 21 L858R | 18.2 (5.6-NE) |
| With CNS metastases | 18.5 (7.5-NE) |
| Without CNS metastases | 32.1 (12.1-NE) |
| 1-/2-/3- year OS, % (95% CI) | 93.8 (82.6-100.0)/ 75 (56.5-99.5)/ 61.9 (41.9-91.4) |
Conclusions
This chemo-free, oral regimen of osi plus anlo showed prolonged PFS as 1L treatment for EGFRm advanced NSCLC pts, and the safety profile was tolerable and manageable.
Clinical trial identification
NCT04770688.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
AstraZeneca and Chiatai Tianqing.
Disclosure
All authors have declared no conflicts of interest.