EGFR-TKI for NSCLC

China NMPA approves Rezivertinib (BPI-7711) for patients with second-line treatment on May 20, 2024

Mode of Action

• A third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeting both EGFR-sensitizing mutations and EGFR T790M mutation. .
• Overcome the drug resistance and toxicity problems of 1st/2nd generation EGFR-TKIs.
• Well tolerated and highly effective in NSCLC patients with advanced or recurrent EGFR/T790M mutation progressed after 1st generation EGFR-TKI treatment.
• Demonstrated a promising efficacy on brain metastases.
• A total of 636 patients were screened and 226 were finally enrolled. Clinical study data showed excellent efficacy (also as the only one clinical trial in the third generations of EGFR-TKI which accepted positive peripheral blood sample, which is closer to the real-world screening method of most patients), good safety and tolerability, and outstanding efficacy for patients with brain metastasis. BPI-7711 is expected to be best-in-class third-generation EGFR-TKI for the treatment of patients with brain metastases.
• A total of 226 patients were enrolled from Jul 5, 2019, to Jan 22, 2020. 91 (40.3%) patients had brain metastases. The tissue sample and plasma sample were positive for EGFR T790M in 120 (53.1%) and 116 (51.3%) patients, respectively. By the data cutoff date on Dec 23, 2021, the ORR by BICR was 64.6% (95%CI:58.0-70.8) and DCR was 89.8% (95%CI:85.1-93.4). The median DoR was 12.5 (95%CI:10.0-13.9) months and median PFS was 12.2 (95%CI:9.6-13.9) months. The median OS was 23.9 (95%CI:20.0-NC) months. Subgroup ORR: exon 19 deletion 72.4% (95%CI:64.4-79.5), L858R 51.9% (95%CI:40.4-63.3), tissue T790M positive 70% (95%CI:61.0-78.0), plasma T790M positive 56.9% (95%CI:47.4-66.1). Subgroup PFS: exon 19 deletion 12.4 (95%CI:8.8-15.1) months, L858R 10.3 (95%CI:8.3-13.9) months, tissue T790M positive 13.9 (95%CI:11.3-17.9) months, plasma T790M positive 9.6 (95%CI:7.0-11.0) months. Among 91 patients with CNS metastases, 29 patients had at least one brain target lesion whose CNS-ORR and CNS-DCR were 69.0% (95%CI:49.2-84.7) and 100% (95%CI:88.1-100), respectively. Time to progression of CNS was 16.5 (95%CI:9.7-NC) months. 188 of 226 (83.2%) patients had at least one adverse drug reaction, with the most common being white blood cell count decreased (27.9%), platelet count decreased (23.0%), anemia (22.6%). No interstitial lung disease was reported. (2022 ASCO Meeting, Abstract 9098)

Status

• Pre-clinical development complete.
• Chinese clinical trial application (CTA) filed and approved in 2017.
• Phase I clinical trial recruitment has been completed in November, 2019.  172 patients were enrolled.  Final data analysis and reports are in progress.
• Pivotal phase IIb trial was launched in March 2, 2019. By December 2019, 212 patients have been enrolled and trial recruitment will complete in January 2020.
• Pre-IND meeting with US FDA has been scheduled in February 2020.
• Pivotal phase III trial is targeting the treatment-naive EGFR mutation NSCLC patients. Phase III trial has started and expected to be completed in 18-24 months.
• Phase IIb Clinical Trial (2nd Line Treatment) Interim Analysis Data has been submitted in NDA.
• Phase III Clinical Trial (1st Line Treatment) patient enrolling now.
• NDA application was accepted by NMPA (China National Medical Products Administration) in January 2024.
• China NMPA approves RezivertinibÒ (BPI-7711) for patients with second-line treatment on May 20, 2024.