Semena (befotertinib)

As of August 23, 2023, the first generation EGFR-TKIs, gefitinib, icotinib, and erlotinib; the second generation EGFR-TKIs, afatinib and dacomitinib; and the third generation EGFR-TKIs, osimertinib, almonertinib, furmonertinib and befotertinib were all approved for marketing by China National Medical Products Administration (NMPA). In addition, multiple domestic third-generation EGFR-TKIs are undergoing clinical trials, such as rezivertinib (BPI-7711), limertinib (ASK120067), and oritinib (SH-1028). Meanwhile, mobocertinib and sunvozertinib, which targets EGFR 20ins mutations, were also approved by NMPA. With the increasing variety of EGFR-TKIs approved for marketing subsequently, it brings confusion to clinicians when choosing specific medications, and there is an urgent need to develop relevant treatment guidelines. Hence, the Medical Oncology Branch of China International Exchange and Promotive Association for Medical and Health Care and the Chinese Association for Clinical Oncologists convened experts to integrate the research results of various EGFR-TKIs, and proposed the "China clinical practice guideline for epidermal growth factor receptor tyrosine kinase inhibitors in stage Ⅳ non-small cell lung cancer (version 2023)", to provide reference for better clinical practice.

Conclusions Befotertinib exhibited notable efficacy in both dose cohorts, showing a comparable OS benefit with other 3rd-generation EGFR TKIs in cohort A (50 mg), while even greater OS benefits in cohort B. Further, safety remained manageable and consistent with prior assessments. Overall, befotertinib maintained its remarkable efficacy with a manageable safety profile in pretreated pts with confirmed T790M mutation-positive NSCLC.

P1, N=172, Not yet recruiting, Betta Pharmaceuticals Co., Ltd.

Befotertinib demonstrated superior efficacy compared with icotinib in first-line treatment for patients with EGFR mutation-positive NSCLC. Although serious adverse events were more common in the befotertinib than the icotinib arm, the safety profile of befotertinib was manageable overall.

No abstract available

No abstract available

P2, N=286, Active, not recruiting, InventisBio Co., Ltd | Trial primary completion date: Nov 2020 --> Aug 2021

Befotertinib has shown favorable efficacy and manageable safety in pts with locally advanced or metastatic NSCLC harboring T790M mutation as a second-line option in the Chinese population.

P1, N=50, Active, not recruiting, InventisBio Co., Ltd | Trial completion date: Aug 2021 --> Dec 2022

D-0316 is safe, tolerable, and effective for patients with locally advanced/metastatic NSCLC with the EGFR T790M mutation who previously received EGFR-TKI.

P2, N=30, Recruiting, Betta Pharmaceuticals Co., Ltd. | Not yet recruiting --> Recruiting

P2, N=30, Not yet recruiting, Betta Pharmaceuticals Co., Ltd.

Progression: The study was conducted in 40 centers in China. As of 18 December, 2020, the recruitment was completed.

P1, N=50, Active, not recruiting, InventisBio Inc. | Trial primary completion date: May 2021 --> Aug 2020

P2, N=286, Active, not recruiting, InventisBio Inc. | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2021 --> Nov 2020

P2/3, N=362, Active, not recruiting, Betta Pharmaceuticals Co., Ltd. | Recruiting --> Active, not recruiting | Trial completion date: Dec 2021 --> Dec 2023 | Trial primary completion date: Feb 2021 --> Dec 2021

P1, N=50, Active, not recruiting, InventisBio Inc. | Trial completion date: Mar 2021 --> Aug 2021 | Trial primary completion date: Dec 2020 --> May 2021

In this review, we profiled many of the third-generation EGFR TKIs in late stage clinical development (e.g. almonertinib, lazertinib, alflutinib, rezivertinib, ASK120069, SH-1028, D-0316 and abivertinib) of their interim results of phase 1-3 trials and their chemical structures when publicly available. Additionally, we summarized the results of clinical trials that previously reported third-generation EGFR TKIs (rociletinib, olmutinib, nazartinib, maverlertinib) including phase 3 results of rociletinib and naquotinib. We further profiled the next-generation combination clinical trial design of third-generation EGFR TKIs including FLAURA2 (NCT04035486), MARIPOSA (NCT04487080), ACROSS1 (NCT04500704) and ACROSS2 (NCT04500717).

P1, N=50, Active, not recruiting, InventisBio Inc. | Trial completion date: Oct 2020 --> Mar 2021 | Trial primary completion date: Aug 2020 --> Dec 2020

P1, N=50, Active, not recruiting, InventisBio Inc. | Trial completion date: Jul 2020 --> Oct 2020 | Trial primary completion date: Apr 2020 --> Aug 2020

P2/3, N=360, Recruiting, Betta Pharmaceuticals Co., Ltd. | Not yet recruiting --> Recruiting

P1, N=50, Active, not recruiting, InventisBio Inc. | Recruiting --> Active, not recruiting | Trial completion date: Mar 2020 --> Jul 2020 | Trial primary completion date: Dec 2019 --> Apr 2020

P2, N=286, Recruiting, InventisBio Inc. | Trial primary completion date: Dec 2019 --> Dec 2021

P1, N=50, Recruiting, InventisBio Inc.