WCLC 2025 - Posters & ePosters-P3.12.22 A Phase II Study of Sunvozertinib Combined With Anlotinib in Treatment-Naïve NSCLC With EGFR Sensitive Mutations and Co-Mutations (WU-KONG32)

P3.12.22 A Phase II Study of Sunvozertinib Combined With Anlotinib in Treatment-Naïve NSCLC With EGFR Sensitive Mutations and Co-Mutations (WU-KONG32)

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This Phase 1 study evaluated the safety and efficacy of sunvozertinib combined with anlotinib in treatment-naïve advanced non-small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations (exon 19 deletions, L858R, T790M) along with co-mutations such as TP53. EGFR tyrosine kinase inhibitors (TKIs) often show reduced efficacy in the presence of co-mutations, leading to poorer outcomes. The combination targets both EGFR mutations (via sunvozertinib, a novel EGFR-TKI) and angiogenesis (via anlotinib, a multi-target TKI with anti-VEGF effects), hypothesized to produce synergistic anti-tumor effects and alleviate drug resistance.<br /><br />The study had two parts: a safety run-in phase (Part A) with 10 patients receiving sunvozertinib 300 mg daily plus anlotinib 8 mg daily (days 1-14 of a 21-day cycle), and a dose-expansion phase (Part B). If more than three dose-limiting toxicities (DLTs) were seen in Part A, the sunvozertinib dose would be reduced to 200 mg. Treatment continued until disease progression or unacceptable toxicity.<br /><br />As of March 2025, 16 patients enrolled (median age 64 years, 56% female, 25% with brain metastases). In Part A, only one DLT (grade 2 interstitial lung disease) occurred with no serious adverse events reported. Common treatment-emergent adverse events included diarrhea, rash, and anorexia, mostly grade 1-2; grade 3 events occurred in 37.5% without treatment discontinuation or deaths, indicating the regimen was well tolerated. The recommended combination dose (RCD) was established as sunvozertinib 300 mg plus anlotinib 8 mg.<br /><br />Among nine evaluable patients, the objective response rate (ORR) was 77.8%, with 7 partial responses and 2 stable diseases, achieving a disease control rate (DCR) of 100%.<br /><br />In conclusion, sunvozertinib combined with anlotinib demonstrated manageable safety and promising efficacy in treatment-naïve NSCLC patients with EGFR mutations and co-mutations, warranting further clinical investigation to address unmet needs in this population.

Asset Subtitle

Yongchang Zhang

Meta Tag

Speaker Yongchang Zhang

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

sunvozertinib

anlotinib

non-small cell lung cancer

NSCLC

EGFR mutations

TP53 co-mutations

tyrosine kinase inhibitors

dose-limiting toxicities

objective response rate

disease control rate