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

Drug-Drug Interaction Study of Befotertinib Capsules in Healthy Participants. (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Betta Pharmaceuticals Co., Ltd.

New P1 trial

Efficacy and Safety of Different Dosing Regimens of Befotertinib in NSCLC Patients With Brain Metastases (IASLC-WCLC 2026) - P4 | "This cohort will evaluate the efficacy and safety of Befotertinib 75-100 mg QD. Patient enrollment for this study is currently ongoing.Chinese clinical Trial Registration Number: ChiCTR2400085346."

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

Comparative efficacy and safety of first, second, and third-generation EGFR tyrosine kinase inhibitors in treatment-naïve EGFR-mutant advanced non-small cell lung cancer: a systematic review and network meta-analysis of randomized controlled trials. (PubMed, J Egypt Natl Canc Inst) - "While several EGFR-TKIs improved efficacy over first-generation agents, no single treatment was clearly superior across all efficacy and safety outcomes. Osimertinib showed consistent efficacy, while its safety advantage became evident in the sensitivity analysis excluding FLAURA China."

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

Befotertinib (D-0316) versus icotinib as first-line therapy for patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer: a multicentre, open-label, randomised phase 3 study. (PubMed, Lancet Respir Med) - P2/3 | "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."

Journal • Metastases • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Efficacy and safety of befotertinib (D-0316) in patients with EGFR T790M mutated non-small cell lung cancer that had progressed after prior EGFR TKI therapy: A phase 2, multicenter, single-arm, open-label study. (PubMed, J Thorac Oncol) - P2, P2/3 | "Befotertinib of 75-100 mg has satisfying efficacy and manageable toxicity in patients with locally advanced or metastatic NSCLC harboring T790M mutation with resistance to first- or second- generation EGFR TKIs. A phase 3 randomized trial is underway (NCT04206072)."

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

Befotertinib vs Icotinib as First-Line Treatment for EGFR-mutated Advanced NSCLC: Final Overall Survival Analysis of the Phase III Study (IASLC-WCLC 2026) - "The safety profile was consistent with previous reports, and no new safety signals were identified. Conclusions : Befotertinib demonstrated sustained benefits in PFS and DOR with a manageable safety profile; OS was not statistically different between arms, likely influenced by the sample size and the higher usage of subsequent third-generation EGFR TKIs in the icotinib arm."

Clinical • Metastases • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR

Neoadjuvant befotertinib plus vorolanib in resectable stage II-IIIB EGFR-mutant NSCLC: a study protocol for the prospective, single-arm phase I/II trial. (PubMed, Transl Lung Cancer Res) - P1/2 | "The study may help define whether intensification of neoadjuvant targeted therapy can improve pathological regression in this molecularly selected population. Chinese Clinical Trial Registry (ChiCTR2500103324)."

Journal • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

First-line third-generation EGFR-TKIs for advanced EGFR-mutated non-small cell lung cancer: a systematic review and network meta-analysis of randomized controlled trials. (PubMed, J Thorac Dis) - "All investigated third-generation agents (aumolertinib, osimertinib, furmonertinib, befotertinib, limertinib, rilertinib, lazertinib, and rezivertinib) demonstrated superior PFS compared to first-generation TKIs. Most third-generation TKIs offer superior PFS compared to first-generation agents, with comparable efficacy observed across the third-generation agents. Safety profiles, specifically regarding high-grade adverse events, appear similar between third- and first-generation TKIs."

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

BE-MASTER: Befotertinib Plus Chemotherapy With an MRD-guided Adaptive Strategy for Treatment Escalation and Response Optimization in EGFR-mutated NSCLC Patients (clinicaltrials.gov) - P2 | N=124 | Not yet recruiting | Sponsor: Guangzhou University of Traditional Chinese Medicine

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

Attenuation of ABCG2-dependent drug efflux by befotertinib restores chemosensitivity in multidrug-resistant non-small cell lung cancer cells. (PubMed, Biomed Pharmacother) - "Through this mechanism, befotertinib acts as a functional inhibitor of ABCG2, restoring intracellular drug accumulation and enhancing cytotoxic responses. Collectively, these findings indicate that befotertinib may serve as a chemosensitizing agent to overcome MDR in NSCLC with high ABCG2 expression, supporting further evaluation in combination therapeutic strategies."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ABCG2 • EGFR

Perioperative strategies for resectable EGFR-Mutant NSCLC: evidence hierarchy and clinical decision-making. (PubMed, Cancer Treat Rev) - "We compare established and emerging perioperative approaches, including aumolertinib, furmonertinib, befotertinib, and neoadjuvant or perioperative osimertinib-based strategies, while underscoring that encouraging early signals should not be equated with established survival benefit before mature event-free survival or overall survival data are available. We also address three unresolved questions: the role of adjuvant chemotherapy in the osimertinib era, the extent to which targeted therapy should move into the neoadjuvant setting, and whether minimal residual disease assessment may eventually support treatment personalization. Overall, current evidence supports adjuvant osimertinib as the reference standard for resected EGFR-mutant NSCLC, whereas other third-generation adjuvant TKIs and perioperative targeted strategies remain promising but should be interpreted according to the maturity of their supporting data and the presence or absence of overall survival benefit."

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

Study on the incidence of venous thromboembolism in patients with locally advanced or metastatic NSCLC harboring EGFR-sensitive mutations treated with befotertinib with or without rivaroxaban (ChiCTR) - P4 | N=1382 | Sponsor: National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College; National Cancer Center/Cancer Hospital,Ch

New P4 trial • Cardiovascular • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Venous Thromboembolism

ctDNA-guided dynamic monitoring for befotertinib combined with radiotherapy in oligometastatic non-small cell lung cancer with EGFR mutations: a single-arm, multicenter, exploratory study (ChiCTR) - P2 | N=84 | Sponsor: The Fourth Hospital of Hebei Medical University; The Fourth Hospital of Hebei Medical University

Circulating tumor DNA • New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

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

Befotertinib restored chemosensitivity to multidrug-resistant cancer cells by inhibiting the drug efflux activity of ABCB1. (PubMed, J Pharm Pharmacol) - "These results identify befotertinib as a functional inhibitor of ABCB1 with the capacity to reverse MDR. The findings support its potential as a repurposed agent for combination therapy in tumors with high ABCB1 expression, offering a practical strategy to enhance chemotherapy efficacy."

Journal • Oncology • ABCB1 • EGFR

Therapy for Advanced NSCLC With EGFR 19delins Mutation (clinicaltrials.gov) - P1 | N=94 | Not yet recruiting | Sponsor: Fuzhou General Hospital

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

Epidermal growth factor receptor tyrosine kinase inhibitor for the treatment of non-small cell lung cancer in the past 30 years (1997-2026). (PubMed, Chin Med J (Engl)) - "Since 1997, EGFR tyrosine kinase inhibitors (EGFR-TKIs) have evolved from first-generation agents, such as gefitinib, erlotinib, and icotinib, to second-generation agents like afatinib and dacomitinib, now to third-generation agents, including osimertinib, aumolertinib, furmonertinib, befotertinib, rezivertinib, rilertinib, limertinib, lazertinib, mifanertinib for EGFR L858R, sunvozertinib for EGFR exon 20 insertion (20ins), and zorifertinib for EGFR-sensitive mutation with brain metastases. Over the past 30 years, substantial advancements have been made in the comprehensive management of EGFR-mutant NSCLC. This systemic review provides the history of the development of EGFR-TKI therapy for NSCLC from 1997 to 2026, highlighting clinical milestones, emerging therapies, and future directions in this rapidly evolving field."

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

ctDNA Monitoring Guides the Treatment of NSCLC With Befotertinib Combined With Radiotherapy (clinicaltrials.gov) - P2 | N=84 | Not yet recruiting | Sponsor: Hebei Medical University Fourth Hospital

Circulating tumor DNA • New P2 trial • 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 (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