Abstract 67P
Background
Sunvozertinib is a highly selective EGFR tyrosine kinase inhibitor (TKI) targeting various EGFR mutations. Previous reports idicate Sunvozertinib monotherapy has shown promising and durable anti-tumor activity in EGFR sensitizing mutations (EGFRm) after failure of standard EGFR- TKI treatment. Preclinical studies reported that the combination of an EGFR-TKI plus a VEGF inhibitor (VEGFi) resulted in a synergistic effect. This is the first report on sunvozertinib combination therapy with an anti-angiogenic drug.
Methods
This open-label, single arm, phase II study is expected to enroll 45 patients with EGFR sensitizing mutations who failed standard EGFR-TKI treatment. This study has two parts. Part A adopted a dosereduction safety run-in design to assess the tolerability and safety of Sunvozertinib combined with Anlotinib. The initial dosing of Sunvozertinib was 300 mg p.o. daily in combination with Anlotinib 12 mg p.o. daily on days 1–14 of a 21-day cycle. Part B is an expansion period at the recommended combination dose (RCD). The primary endpoint is objective response rate (ORR). Secondary endpoints include disease control rate (DCR), progression free survival, overall survival and safety profile. We added exploratory endpoints for the exploration of resistance mechanisms based on NGS testing and organoid drug sensitivity assessment.
Results
As of Dec 25, 2024 (DCO), 10 patients had successfully passed dose reduction safety run-in part and 3 patients were enrolled in dose expansion part. Sunvozertinib combined with Anlotinib was well tolerated, no DLT event occurred, and the RCD was Sunvozertinib 300 mg p.o. daily in combination with Anlotinib 12 mg p.o. daily on days 1–14 of a 21-day cycle. Overall, 12 patients completed first assessment. The ORR was 33.3%, DCR was 100%. The common (≥30%) TEAEs were diarrhea, rash, proteinuria, and fatigue. No Sunvozertinib-related discontinuations or reductions and no treatment related deaths were observed.
Conclusions
Sunvozertinib combined with Anlotinib is well tolerated and has demonstrated encouraging antitumor activity in NSCLC patients with EGFR mutations who failed prior EGFR-TKIs therapies. Enrollment is ongoing and results will be updated at the meeting.
Clinical trial identification
NCT06182761.
Legal entity responsible for the study
The authors.
Funding
Dizal Pharmaceutical Co Ltd.
Disclosure
All authors have declared no conflicts of interest.