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

Befotertinib (D-0316) plus icotinib as first-line therapy for patients with EGFR-mutated advanced non-small-cell lung cancer (ESMO Asia 2025) - P=N/A | "This study demonstrates the efficacy of first-line befotertinib plus icotinib in EGFR-mutated advanced NSCLC. To our knowledge, this is the first clinical trial to adjust TKI doses based on plasma ctDNA clearance status. Results showed encouraging antitumor activity, high ctDNA clearance rates, and a manageable safety profile."

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

First-Line Third-Generation EGFR Tyrosine Kinase Inhibitor Monotherapy for Advanced EGFR-Mutated Non-Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis. (PubMed, MedComm (2020)) - "Osimertinib (HR, 0.90; 95% CrI, 0.83-0.99) and lazertinib (HR, 0.89; 95% CrI, 0.79-1.00) showed overall survival benefits over first-gen TKIs. Furmonertinib, aumolertinib, and osimertinib had lower rates of severe treatment-related adverse events (TRAEs), while befotertinib exhibited the highest risk of grade ≥3 TRAEs (RR, 3.96; 95% CrI, 2.35-7.17). This study is the first head-to-head comparison of third-gen EGFR-TKIs using a Bayesian network meta-analysis, offering critical insights into efficacy and safety. Our results support personalized selection of third-gen EGFR TKIs for patients with advanced EGFR-mutated NSCLC, particularly for subpopulations with CNS metastases or different mutation subtypes."

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

Sequential Chemotherapy With Befotertinib in Non-Small Cell Lung Cancer (NSCLC) Patients With Resistance to Third-Generation EGFR-TKI (clinicaltrials.gov) - P2 | N=28 | Recruiting | Sponsor: Betta Pharmaceuticals Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Sequential Chemotherapy With Befotertinib in Non-Small Cell Lung Cancer (NSCLC) Patients With Resistance to Third-Generation EGFR-TKI (clinicaltrials.gov) - P2 | N=28 | Not yet recruiting | Sponsor: Betta Pharmaceuticals Co., Ltd.

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

Efficacy of Conventional and Novel Tyrosine Kinase Inhibitors for Uncommon EGFR Mutations-An In Vitro Study. (PubMed, Cells) - "The growth inhibitory effects of five novel 3G-TKIs, almonertinib, lazertinib, furmonertinib, rezivertinib, and befotertinib, in addition to currently available TKIs, were evaluated. In conclusion, afatinib exhibited broad activity and some 3G-TKIs showed promising efficacy in the front-line setting. Lazertinib is a potential second-line option after acquisition of resistance to afatinib or osimertinib."

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

Efficacy and Safety of Befotertinib Plus Icotinib in Advanced NSCLC With Uncommon EGFR Mutations: A Phase II Study (Icombine) (IASLC-WCLC 2025) - P2 | "Although uncommon EGFR mutations (accounting for 10-15% of EGFR-mutant NSCLC, such as G719X, L861Q, and S768I) show partial efficacy to approved EGFR tyrosine kinase inhibitors (TKIs) like afatinib and osimertinib, the optimal therapeutic strategy for these mutations remains undetermined, with no consensus in clinical practice. Preclinical and clinical evidence has shown that combining first-/second- and third-generation EGFR-TKIs may delay resistance (e.g., osimertinib plus gefitinib demonstrated an 88.9% objective response rate [ORR] in phase I/II trials), but such strategies remain unexplored in uncommon mutations...The primary endpoint is ORR assessed by RECIST v1.1, with secondary endpoints including PFS, disease control rate (DCR), overall survival (OS), and safety evaluations (incidence and severity of adverse events). Recruitment for this trial is currently ongoing."

Clinical • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • Thrombocytopenia • EGFR

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

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

A prospective, single-arm phase I/II clinical study of befotertinib in combination with vorolanib neoadjuvant in patients with stage II-IIIB EGFR-positive non-small cell lung cancer (ChiCTR) - P1/2 | N=39 | Not yet recruiting | Sponsor: Zhejiang Cancer Hospital; Zhejiang Cancer Hospital

New P1/2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

A multicenter, open-label, single-arm phase I/II study to assess the efficacy and safety of WSD0922-FU in patients with EGFR C797Sm+ advanced non-small cell lung cancer (NSCLC) in China (NCT06631989). (ASCO 2025) - P1, P1/2 | "Funded by No funding sources reported Clinical Trial Registration Number: NCT06631989 Background: Although 3rd-generation EGFR TKIs, such as Osimertinib, Almonertinib, Furmonertinib, Befotertinib etc. are highly effective in front-line metastatic EGFR-mutated (EGFRm) NSCLC, treatment resistance ultimately occurs, including the emergence of the on-target C797S mutation for which there are no approved TKIs. Enrollment in this study for dose expansion cohorts is ongoing and 15 sites are open across China. Clinical trial information: NCT06631989."

Clinical • Metastases • P1/2 data • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

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