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Phase II Dose-Randomized Study of Sunvozertinib in Platinum-Pretreated Non-Small Cell Lung Cancer With Epidermal
James Chih-Hsin Yang1, Mengzhao Wang2, Ludovic Doucet3
1National Taiwan University Cancer Center and National Taiwan University Hospital, Taipei, Taiwan.
Purpose:
WU-KONG1B (ClinicalTrials.gov identifier: NCT03974022) is a multinational phase II, dose-randomized study to assess the antitumor efficacy of sunvozertinib in pretreated patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations (exon20ins).
Methods:
Eligible patients with advanced-stage EGFR exon20ins NSCLC were randomly assigned by 1:1 ratio to receive sunvozertinib 200 mg or 300 mg once daily (200 and 300 mg-rand cohorts). After predefined interim analysis, additional patients were enrolled and treated with the 300 mg dose once daily. The primary end point was blinded independent review committee (IRC)-assessed confirmed objective response rate (cORR), and the key secondary end point was duration of response (DoR).
Results:
Among 85, 89, and 107 efficacy-evaluable patients in 200 mg-rand, 300 mg-rand, and 300 mg-all (including randomly assigned and nonrandomized patients) cohorts, the cORRs were 45.9% (97.5% CI, 33.6% to 58.5%), 47.2% (97.5% CI, 35.1% to 59.5%), and 45.8% (97.5% CI, 34.8% to 57.0%), respectively, per IRC assessment. The predefined null hypothesis was rejected with statistical significance (P < .0001). Comparing 300 and 200 mg-rand cohorts, higher cORRs were observed in patients with baseline brain metastasis (52.4% v 28.6%) and previous amivantamab treatment (41.7% v 25%), as well as longer DoR (13.8 v 11.1 months). At 200 and 300 mg once daily, the most common treatment-related adverse events with grade ≥3 included diarrhea (2.2% v 18%), blood creatine phosphokinase increased (6.6% v 12.6%), and anemia (4.4% v 6.3%).
Conclusion:
Sunvozertinib is efficacious at both 200 and 300 mg once daily in treating platinum-pretreated patients with advanced EGFR exon20ins NSCLC. The treatment-related adverse events of sunvozertinib were consistent with an EGFR tyrosine kinase inhibitor, with a more favorable safety profile at 200 mg than 300 mg once daily.
Insights
Sunvozertinib shows efficacy in advanced non-small cell lung cancer with EGFR exon20 insertion mutations. Both 200 mg and 300 mg doses are effective, with the 200 mg dose offering a more favorable safety profile.
Area of Science:
- Oncology
- Pharmacology
Background:
- Advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations (exon20ins) presents a treatment challenge.
- Targeted therapies are crucial for improving outcomes in NSCLC patients with specific genetic alterations.
Purpose of the Study:
- To assess the antitumor efficacy and safety of sunvozertinib in pretreated patients with advanced NSCLC harboring EGFR exon20ins.
- To compare the efficacy of two different doses of sunvozertinib (200 mg and 300 mg once daily).
Main Methods:
- A multinational phase II, dose-randomized study (WU-KONG1B, NCT03974022) enrolled patients with advanced EGFR exon20ins NSCLC.
- Patients were randomized 1:1 to sunvozertinib 200 mg or 300 mg daily. An interim analysis led to additional enrollment in the 300 mg arm.
- The primary endpoint was confirmed objective response rate (cORR) by blinded independent review committee (IRC). Duration of response (DoR) was a key secondary endpoint.
Main Results:
- Confirmed objective response rates (cORRs) were 45.9% (200 mg) and 47.2% (300 mg randomized), with an overall cORR of 45.8% in the 300 mg all-comers group.
- The null hypothesis was rejected with statistical significance (P < .0001).
- Higher cORRs were observed with the 300 mg dose in patients with brain metastases (52.4% vs 28.6%) and prior amivantamab treatment (41.7% vs 25%). DoR was longer with 300 mg (13.8 months vs 11.1 months). Grade ≥3 treatment-related adverse events included diarrhea (18% in 300 mg arm) and elevated creatine phosphokinase (12.6% in 300 mg arm).
Conclusions:
- Sunvozertinib demonstrates efficacy at both 200 mg and 300 mg once daily for platinum-pretreated advanced EGFR exon20ins NSCLC.
- Adverse events were consistent with an EGFR tyrosine kinase inhibitor.
- A 200 mg daily dose of sunvozertinib appears to offer a more favorable safety profile compared to the 300 mg dose.
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