Semena (befotertinib) / InventisBio, Betta Pharma - LARVOL DELTA

Efficacy and safety outcomes of emerging EGFR‑TKIs for patients with non‑small cell lung cancer with EGFR exon 20 insertion mutations: A systematic review and meta‑analysis. (PubMed, Oncol Lett) - "Subgroup analysis revealed the following ORRs: 0.731 (95% CI, 0.560-0.901; I2=0%) for YK-029A; 0.608 (95% CI, 0.511-0.705; I2=0%) for sunvozertinib; 0.602 (95% CI, 0.440-0.764; I2=80.2%) for furmonertinib; 0.602 (95% CI, 0.486-0.718; I2=84.5%) for befotertinib; 0.566 (95% CI, 0.236-0.896; I2=96.3%) for amivantamab; 0.444 (95% CI, 0.215-0.674; I2=0%) for BEBT-109; and 0.256 (95% CI, 0.178-0.334; I2=75.0%) for poziotinib. In conclusion, the emerging EGFR-TKIs for NSCLC with EGFR exon 20 insertion have a promising treatment outcome with a manageable safety profile. However, further analysis is needed when more clinical data are released."

Journal • Retrospective data • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Thrombocytopenia

A clinical review on third and fourth generation EGFR tyrosine kinase inhibitors for the treatment of non-small cell lung cancer. (PubMed, Bioorg Med Chem) - "This review delves into the current clinical status, efficacy, safety profiles, and regulatory approvals of third-generation EGFR TKIs, including Osimertinib, Lazertinib, Furmonertinib, Aumolertinib, Rezivertinib, Befotertinib, Sunvozertinib...Notable fourth-generation candidates such as TQB3804, BPI-361175, BDTX-1535, WJ13404, QLH11811, H002, HS-10375, BBT-207, JIN-A02, and HS-10504 are highlighted for their potential to overcome the C797S mutation...By evaluating the therapeutic potential and limitations of these EGFR TKIs, this review aims to guide future research in the management of EGFR-mutant NSCLC. This acts as guiding beacon for the strategic design and development of third and fourth generation EGFR-TK inhibitors to overcome the drug resistance hurdles in the development of EGFR-TK inhibitors."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

A Bayesian network meta-analysis of EGFR-tyrosine kinase inhibitor treatments in patients with EGFR mutation-positive non-small cell lung cancer. (PubMed, Cancer Pathog Ther) - "We conducted a network meta-analysis of randomized controlled trials comparing osimertinib, lazertinib, aumolertinib, befotertinib, furmonertinib, dacomitinib, afatinib, erlotinib, gefitinib, icotinib, and chemotherapy. Osimertinib is the first choice of treatment with considerable efficacy and safety for EGFR mutation-positive NSCLC. The treatments associated with the best PFS in patients with exon 19 deletions and Leu858Arg mutations were furmonertinib and lazertinib, respectively."

Journal • Retrospective data • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Phase II Clinical Study of Befotertinib in EGFR Non-classical Mutant NSCLC (clinicaltrials.gov) - P2 | N=78 | Recruiting | Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Comparing the Effectiveness and Safety of First-line Interventions in Patients With Advanced Epidermal Growth Factor Receptor-mutant Non-small Cell Lung Cancer, With Particular Focus on Brain Metastatic Status: A Systematic Review and Network Meta-analysis. (PubMed, Clin Oncol (R Coll Radiol)) - "In EMAN patients, osimertinib + CT and amivantamab + lazertinib were associated with optimal PFS and OS, respectively. Among BM patients, osimertinib + CT offered the best PFS benefits. These findings may assist in clinical decision-making and personalized care for EMAN and BM patients. The study is registered on PROSPERO (CRD42024506995)."

Journal • Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

First-line treatment for advanced or metastatic EGFR mutation-positive non-squamous non-small cell lung cancer: a network meta-analysis. (PubMed, Front Oncol) - "The study encompassed the following 19 treatments: Chemotherapy; Afatinib; Afatinib + Cetuximab; Apatinib + Gefitinib; Befotertinib; Cetuximab + Chemotherapy; Erlotinib; Erlotinib + Bevacizumab; Erlotinib + Chemotherapy; Gefitinib; Gefitinib + Chemotherapy; Gefitinib + Olaparib; Icotinib; Icotinib + Chemotherapy; Lazertinib; Naquotinib; Osimertinib; Osimertinib + Bevacizumab; Osimertinib + Chemotherapy. However, due to the limitations in the number and quality of included studies, these conclusions await further validation through more high-quality research. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024562981, identifier CRD42024562981."

Journal • Retrospective data • Review • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Third generation vs first generation EGFR-TKIs in the first line treatment for EGFR-mutated locally advanced or metastatic non-small cell lung cancer: a meta-analysis based on randomized controlled trials. (PubMed, J Cancer) - " We analyzed 15 studies from 6 RCTs on six third-generation TKIs: Osimertinib, Lazertinib, Furmonertinib, Aumolertinib, Naquotinib, and Befotertinib. Except for Naquotinib, TGETs demonstrate superiority over FGETs in treating EGFR-mutated locally advanced or metastatic NSCLC, showing improved survival and responses. However, the increased incidence of AEs necessitates careful consideration."

Journal • Retrospective data • Cardiovascular • Fatigue • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Embolism • Respiratory Diseases • Solid Tumor

Neoadjuvant Befotertinib Combined Bevacizumab or Platinum-based Double Chemotherapy for Resectable Locally-advanced EGFR Mutation-positive Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Peng Zhang

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Clinical benefit evaluation of drug treatment regimens for advanced lung cancer:based on ASCO-VF and ESMO-MCBS. (PubMed, Lung Cancer) - "ASCO-VF and ESMO-MCBS focus on clinical efficacy and consider the adverse effects of drugs and PROs. We look forward to head-to-head studies on the different treatment options and advocate refining the ESMO-MCBS."

Journal • Metastases • Lung Cancer • Oncology • Solid Tumor

Efficacy of Novel Third-Generation Tyrosine Kinase Inhibitors for Uncommon EGFR Mutations- Anin Vitrostudy (IASLC-WCLC 2024) - "Here, we evaluated novel third-generation tyrosine kinase inhibitors (3G-TKIs) including almonertinib(=aumolertinib, lazertinib, alfultinib(=furmonertinib), rezivertinib, and befotertinib) in addition to osimertinib using Ba/F3 models transduced with five uncommon EGFR mutation (Del18, E709K, G719A, S768I, L861Q). Conclusions : Afatinib exhibits broad activity against all uncommon EGFR mutations tested, while 3G-TKIs did not display generation-specific activity but rather drug-specific activity, despite befotertinib, alfultinib, and almonertinib sharing very similar structures with osimertinib. The T790M secondary mutation that emerged after afatinib treatment remain sensitive to lazertinib.We conclude that afatinib is the best drug for uncommon EGFR mutations among currently available EGFR-TKIs."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Befotertinib (D-0316) Plus Icotinib as First-Line Therapy for Patients with EGFR-Mutated Advanced Non-Small-Cell Lung Cancer (IASLC-WCLC 2024) - "Conclusions : This study demonstrates the efficacy of first-line befotertinib plus icotinib in EGFR-mutated advanced NSCLC. To our knowledge, this is the first clinical study to adjust TKIs dose based on whether plasma ctDNA clearance has been achieved, and results showed encouraging antitumor activity, high ctDNA clearance, and well-tolerated safety profile."

Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Befotertinib in first-line treatment for Chinese non-small cell lung cancer patients harboring common EGFR-mutations reveals similar efficacy to other third-generation EGFR-TKIs but somewhat different safety profile. (PubMed, Chin Clin Oncol) - No abstract available

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Befotertinib and Icotinib in Treatment-naive Patients With Advanced EGFR-Mutant Lung Cancer (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: Betta Pharmaceuticals Co., Ltd. | Trial primary completion date: Dec 2023 ➔ Dec 2024 | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Trial primary completion date • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

D-0316 Versus Icotinib in Patients With Locally Advanced or Metastatic EGFR Sensitising Mutation Positive NSCLC (clinicaltrials.gov) - P2/3 | N=362 | Active, not recruiting | Sponsor: Betta Pharmaceuticals Co., Ltd. | Trial completion date: Dec 2023 ➔ Dec 2024

Metastases • Trial completion date • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Befotertinib: one more drug targeting EGFR-the more may be the merrier. (PubMed, Chin Clin Oncol) - No abstract available

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Befotertinib Adjuvant Therapy in Stage IA2-IB NSCLC Patients (clinicaltrials.gov) - P4 | N=592 | Recruiting | Sponsor: Fudan University

Minimal residual disease • New P4 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Potential Utility of a 4th-Generation EGFR-TKI and Exploration of Resistance Mechanisms-An In Vitro Study. (PubMed, Biomedicines) - "Ba/F3 cells with an osimertinib-resistant secondary mutation were refractory to all 3G TKIs tested (alflutinib, lazertinib, rezivertinib, almonertinib, and befotertinib)...HCC827BIR cells had MET gene amplification and were sensitive to a combination of capmatinib (MET-TKI) and BI4020...This study suggests that erlotinib may be more suitable than 4G TKIs to overcome secondary mutations after front-line osimertinib. We found that off-target mechanisms that cause resistance to earlier-generation TKIs will also cause resistance to 4G TKIs."

Journal • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Befotertinib for patients with pretreated EGFR T790M mutated locally advanced or metastatic NSCLC: Final overall survival results from a phase 2 trial. (PubMed, Lung Cancer) - P2 | "Befotertinib demonstrated a more profound OS benefit compared to other 3rd-generation EGFR TKI, despite that cross trial data comparison should be interpreted with caution. The safety profile was manageable and consistent with previously report data in pretreated patients with confirmed T790M mutation-positive NSCLC."

Journal • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Phase II study of befotertinib (D-0316) in previously treated #EGFR T790M NSCLC @LungCaJournal. At 50mg, OS 23.9m (18.6 with brain mets, 26.4m without) and 22.2% G3+ TRAEs. At 75-100mg, OS 31.5m (23m with brain mets, 35.5m without) and 31.7% G3+ TRAEs.

IcomBine: Befotertinib and Icotinib for NSCLC With Uncommon EGFR Mutations (clinicaltrials.gov) - P2 | N=23 | Recruiting | Sponsor: Xue Hou

Metastases • New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

OKAIN: A comprehensive oncology knowledgebase for the interpretation of clinically actionable alterations (AACR 2024) - "OKAIN acts as a precision oncology knowledgebase for the assessment of clinically actionable alterations, integrating exhaustive data related to cancer-associated genomic variants and therapeutic efficacy. It is a beneficial tool for medical professionals and patients, providing an enhanced means of understanding and approaching precision oncology."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

D-0316 in Patients With EGFR Positive Non Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=290 | Completed | Sponsor: InventisBio Co., Ltd | Active, not recruiting ➔ Completed | Trial completion date: Dec 2023 ➔ May 2023

Metastases • Trial completion • Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Final overall survival (OS) results of befotertinib in patients with pretreated EGFR T790M-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) (ESMO Asia 2023) - P2 | "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."

Clinical • Late-breaking abstract • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

China clinical practice guideline for epidermal growth factor receptor tyrosine kinase inhibitors in stage â…£ non-small cell lung cancer (version 2023) (PubMed, Zhonghua Yi Xue Za Zhi) - "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 guideline • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • EGFR

Befortinib approved as first-line indication for non-small cell lung cancer Betta Pharmaceuticals: No clear intention to apply for medical insurance yet (eet-china.com) - "On the 12th, Befotertinib Mesylate Capsules (Semena, hereinafter referred to as 'befotertinib')...received approval from The 'Drug Registration Certificate' issued by the National Medical Products Administration (NMPA) officially announced that befotertinib has been approved for marketing in China for the indication of first-line treatment of non-small cell lung cancer (NSCLC)....Regarding whether befotertinib plans to apply for inclusion in medical insurance, personnel from the Securities Department of Betta Pharmaceuticals told a reporter from the Science and Technology Innovation Board Daily that there is currently no clear trend and no definite news has been received....'even if there is a plan to apply for medical insurance for befotertinib, it should only be applied for the indication of second-line treatment of NSCLC first'."

Non-US regulatory • Reimbursement • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor