Abstract 1238P
Background
Osimertinib has been demonstrated superior PFS and OS compared to 1st-generation EGFR-TKIs. There is little information on efficacy and safety of combined therapy with Anlotinib which is an oral multiple-target TKI (inhibit VEGFR2/3, FGFR1-4, PDGFR α/β, c-Kit, and Ret) in advanced EGFRm NSCLC patients.
Methods
This open-label, single arm, phase Ib/IIa study is expected to enroll 25 treatment-naïve patients of locally advanced or metastatic non-squamous EGFRm NSCLC. The phase Ib adopted the rolling six design to assess the tolerability and safety of Osimertinib combined with Anlotinib. The dosing of Osimertinib was 80mg p.o. daily in combination with Anlotinib which administrated 8mg, 10mg and 12mg p.o. daily from day 1 to day 14 (21 days per cycle) in each cohort respectively. Phase IIa is an expansion cohort at the recommended phase II dose (RP2D). The primary endpoint of this study is objective response rate (ORR). Secondary endpoints include disease control rate (DCR), depth of response, progression free survival, overall survival rate at 12 months and safety profile.
Results
As of the 25th, Apr 2021 (DCO), 12 patients were allocated in dose escalation part and 7 patients in dose expansion part. Osimertinib in combination with Anlotinib was well tolerated, and the RP2D was Osimertinib 80mg p.o. daily in combination with Anlotinib 12mg p.o. daily from day 1 to day 14 (21 days per cycle). Overall, 8 patients completed first assessment. The ORR was 87.5% (95% CI 52.9, 97.8), DCR was 100% (95% CI 67.6, 100.0) and median depth of response was 35.0% (range 26%-71%). At the DCO, 18 patients remained on treatment and 1 patient discontinued treatment due to AE. Treatment-emergent AEs (TEAEs) occurred in 6 patients (50%) and 1 patient experienced 1 grade 3 SAE (pneumothorax). The common (≥10%) TEAEs was stomatitis (n=4, 33.3%). No Osimertinib-related discontinuations or interruption and no treatment related deaths were observed.
Conclusions
Osimertinib in combination with Anlotinib is well tolerated and has demonstrated encouraging antitumor activity in treatment naïve EGFRm advanced NSCLC patients. The phase IIa part enrollment is currently ongoing and results will be updated later in the meeting.
Clinical trial identification
NCT04770688.
Editorial acknowledgement
Legal entity responsible for the study
Shanghai Chest Hospital.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.