Rui Bi Da (rezivertinib) / Beta Pharma, CSPC Pharma - LARVOL DELTA

Single-cell RNA-seq and metabolomic profiling reveal stage-specific metabolic reprogramming in EGFR-mutant non-small cell lung cancer brain metastasis (ESMO Asia 2025) - P1/2 | "Additionally, we conducted plasma metabolomic profiling with 186 EGFR-mutant NSCLC patients enrolled in the Rezivertinib Phase I/IIa clinical trial (NCT03386955). The H1975-P3 model demonstrated significantly enhanced BM capacity (P3 vs. P1/P2: D14, p=0.004; D28, p=0.022)... We established a robust EGFR-mutant NSCLC BM experimental model and delineated the dynamic evolution during BM process. Our findings reveal BM-specific metabolic reprogramming and identify potential diagnostic biomarkers, offering novel insights for improving BM management in NSCLC."

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

DRUG SCREENING IDENTIFIED REZIVERTINIB AS BBB-PENETRANT COMPOUNDS WITH ANTITUMOR ACTIVITY IN PEDIATRIC MEDULLOBLASTOMA CELL LINES (SIOP 2025) - "These findings highlight the potential of EGFR-targeted therapies for high-risk medulloblastoma subgroups and pave the way for further preclinical and clinical investigations. Funding: A Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) -Grant: 2022/09037-3; INCT BioOncoPed - Grant 406484/2022-8."

Preclinical • Brain Cancer • CNS Tumor • Endocrine Cancer • Medulloblastoma • Oncology • Pediatrics • Solid Tumor • SHH • TP53 • USP13

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

Rezivertinib in Advanced NSCLC Patients With EGFR T790M Mutation via Tissue/Plasma Samples: Pooled Analysis of 2 Clinical Studies (IASLC-WCLC 2025) - "Patients with tissue-positive but plasma-negative EGFR T790M mutation showed better efficacy than those with both tissue and plasma EGFR T790M positivity. Plasma EGFR T790M positivity at baseline might predict the worse treatment outcome for rezivertinib in this patient population."

Metastases • Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR

Rezivertinib in EGFR-Mutated NSCLC Patients With Cns Metastases: Cns Efficacy From Phase 3 RAZOR Study (IASLC-WCLC 2025) - P3 | "Conclusions : Rezivertinib exhibited superior CNS efficacy compared to gefitinib as a first-line treatment for EGFR-mutated advanced NSCLC with baseline CNS metastases. Safety profile was manageable."

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

The TXNRD1-IGF2BP3 Axis Promotes EGFR-TKI Resistance and Identifies a Therapeutic Vulnerability in NSCLC (IASLC-WCLC 2025) - "The HCC827 rezivertinib-resistant cell line (RR) was generated by continuous exposure to rezivertinib (BPI-7711) until reaching 100-fold of the initial IC50...Conclusions : This study reveals a novel mechanism of EGFR-TKI resistance mediated by the Trx1/TrxR1 system and the TXNRD1-IGF2BP3 axis in NSCLC. Targeting TrxR1 with Auranofin could restore sensitivity to EGFR-TKI, highlighting a potential therapeutic strategy to overcome resistance."

CNS Disorders • Lung Cancer • Non Small Cell Lung Cancer • Psychiatry • Solid Tumor • IGF2BP3

Multi-Omics and Single-Cell Insights Reveal a Lysophosphatidic Acid (LPA)-Mediated Resistant Mechanism to Third Generation EGFR-TKI in Non-Small Cell Lung Cancer. (PubMed, Clin Cancer Res) - P1/2 | "Our study highlights the pivotal role of LPA-mediated signaling and metabolic reprogramming in third-generation EGFR-TKI resistance. Targeting LPA production or its downstream pathways may offer novel therapeutic strategies to overcome resistance. This study provides critical metabolic insights for managing EGFR-sensitive-mutant NSCLC."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • TGFB1

UPLIFT: Umbrella Trial of Adjuvant Therapy in Completely Resected High-risk Stage IA-IB NSCLC: Focus on Driver Mutations (clinicaltrials.gov) - P3 | N=270 | Not yet recruiting | Sponsor: The First Affiliated Hospital of Guangzhou Medical University

IO biomarker • New P3 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

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

Multi-omics revealed unique metabolic resistance mechanisms to third-generation EGFR-TKI in EGFR-mutant non-small cell lung cancer (ELCC 2025) - P1/2 | "This study elucidated unique metabolic resistance mechanisms to BPI-7711 in EGFR-mutant NSCLC. The prognostic models developed from identified metabolites demonstrated strong predictive capabilities, underscoring the potential of integrating metabolomics with clinical parameters to enhance treatment strategies."

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

Rezivertinib versus gefitinib as first-line therapy for patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer (REZOR): a multicentre, double-blind, randomised, phase 3 study. (PubMed, Lancet Respir Med) - P3 | "Our findings suggested that rezivertinib is a potential choice for patients with EGFR-mutated locally advanced or metastatic NSCLC as first-line therapy, owing to the superior overall efficacy and subgroup progression-free survival compared with gefitinib in targeted patients. No new safety signals were identified."

Journal • P3 data • Infectious Disease • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • EGFR

Spatial analyses revealed S100P + TFF1 + tumor cells in spread through air spaces samples correlated with undesirable therapy response in non-small cell lung cancer. (PubMed, J Transl Med) - "To assess the role of S100P + TFF1 + tumor cells in therapy response, we included data from two clinical trial cohorts (BPI-7711 for EGFR-TKI therapy and ORIENT-3 for immunotherapy)...This was further validated by multiplex immunofluorescence performed on twenty NSCLC samples. In summary, our study identified S100P as the biomarker for STAS and highlighted the adverse role of S100P + TFF1 + tumor cells in survival outcomes."

IO biomarker • Journal • Tumor cell • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • S100P • TFF1 • TGFB2 • TGFBR2

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

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

A Study of BPI-7711 Capsule in Non-small Cell Lung Cancer Patients (clinicaltrials.gov) - P3 | N=369 | Active, not recruiting | Sponsor: Beta Pharma Shanghai | Trial completion date: Feb 2024 ➔ Dec 2025

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

New drug for EGFR T790M mutation non-small cell lung cancer! “Rezivertinib Mesylate Capsules“ approved for marketing (Sohu.com) - "...The official website of the China National Medical Products Administration (NMPA) announced that it has recently approved the marketing of the Class 1 innovative drug Rezivertinib Mesylate Capsules (BPI-7711, trade name: Rui Bi Da) submitted by Shanghai Beierda Pharmaceutical Co., Ltd. The drug is suitable for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have experienced disease progression during or after treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and have been confirmed to have EGFR T790M mutations."

China approval • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Development and validation of a deep learning-based model to predict response and survival of T790M mutant non-small cell lung cancer patients in early clinical phase trials using electronic medical record and pharmacokinetic data. (PubMed, Transl Lung Cancer Res) - "We utilized the electronic medical record (EMR) and pharmacokinetic parameters of 326 T790M-mutated NSCLC patients, including 283 patients treated with Abivertinib in phase I (n=177, for training) and II (n=106, for validation) clinical trials and an additional validation cohort 2 comprising 43 patients treated with BPI-7711. CoxMoE offers a valuable approach for patient selection by forecasting therapeutic response and PFS utilizing laboratory tests and pharmacokinetic parameters in the setting of early-phase clinical trials. Simultaneously, CoxMoE could predict the efficacy of third-generation EGFR-TKI non-invasively for T790M-positive NSCLC patients, thereby complementing existing EGFR genotype detection."

Journal • PK/PD data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

DSG2+ cancer stem cells co-located with POSTN+ myofibroblasts in the tumor boundary that determines the efficacy of immunotherapy in non-small cell lung cancer (ELCC 2024) - P1/2, P2b, P3 | "Clinical trial identification ORIENT-3 phase III trial (NCT03150875); BPI-7711 phase I (NCT03386955) and phase IIa (NCT03812809)...Within the co-location area, the MDK signaling pathway exhibited the highest activity in cell-cell communication, identifying MDK-NCL as the main ligand-receptor pair. Conclusions This study successfully constructed a CSC signature and demonstrated the co-location of DSG2+ CSCs and POSTN+ myCAF at the tumor boundary, contributing to immunotherapy resistance."

Cancer stem • Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • DSG2 • MMP9 • POSTN

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

Plasma metabolic signatures uncover therapeutic response and prognosis of third-generation EGFR-TKI treatment in patients with NSCLC (ESMO 2023) - "In vitro experiments, Orlistat combined with BPI-7711 had reduced IC50 (508.08nM) in comparison with BPI-7711 alone (1328nM)...Meanwhile, fatty acids downregulated FASN and upregulated CPT1A expression, which may reduce the de nove synthesis of fatty acids and influence fatty acid oxidation. Conclusions This study revealed the metabolic landscape of advanced T790M-mutant NSCLC patients, providing the potential guide of personalized third-generation EGFR-TKI treatment and therapeutic target for overcoming resistance."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CPT1A • FASN • PIK3CA • PIK3CG • RB1 • TP53

A Study of BPI-7711 Capsule in Non-small Cell Lung Cancer Patients (clinicaltrials.gov) - P3 | N=369 | Active, not recruiting | Sponsor: Beta Pharma Shanghai | Trial completion date: Oct 2023 ➔ Feb 2024 | Trial primary completion date: Oct 2022 ➔ Dec 2023

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

Combined Multi-omics Explore the Resistance Mechanism of Third-generation EGFR-TKI BPI-7711 (IASLC-WCLC 2023) - "JAK2-STAT3 was an important signaling pathway in the resistance of third-generation EGFR-TKI BPI-7711, which could promote EMT and enhance invasion as well as migration ability by remodeling the extracellular matrix. STAT3 inhibitor may be a potential therapeutic regimen in third-generation EGFR-TKI resistance."

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

Rezivertinib Generates Promising CNS Efficacy in NSCLC With an EGFR T790M Mutation (Targeted Oncology) - "Rezivertinib (BPI-7711) showed promising clinical central nervous system (CNS) efficacy among patients with advanced non–small cell lung cancer (NSCLC) with EGFR T790M mutation and CNS metastases.​​...Findings showed that in the CNS full analysis set (cFAS), the CNS objective response rate (CNS-ORR) was 32.0% (95% CI, 24.6%-40.1%) and the CNS disease control rate (CNS-DCR) was 42.0% (95% CI, 34.0%-50.3%), while in the CNS evaluable for response set(cEFR), these rates were 68.9% (95% CI, 53.4%-81.8%) and 100% (95% CI, 92.1%-100.0%)."

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

Efficacy and safety of rezivertinib (BPI-7711) in patients with locally advanced or metastatic/recurrent EGFR T790M-mutated NSCLC: A phase IIb, multicenter, single-arm, open-label study. (ASCO 2022) - "Rezivertinib demonstrated promising efficacy and favorable safety for locally advanced or metastatic/recurrent NSCLC patients with EGFR T790M mutation."

Clinical • P2b data • Anemia • Hematological Disorders • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • EGFR

Efficacy and safety of Rezivertinib (BPI-7711) in patients with locally advanced or metastatic/recurrent EGFR T790M mutated NSCLC: a phase IIb study. (PubMed, J Thorac Oncol) - P2b | "Rezivertinib demonstrated promising efficacy and favorable safety profile for locally advanced or metastatic/recurrent NSCLC patients with EGFR T790M mutation."

Journal • P2b data • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • EGFR