ifebemtinib (IN10018) / InxMed, Boehringer Ingelheim - LARVOL DELTA

IN10018 With Nab-Paclitaxel and Cadonilimab for Metastatic or Recurrent Gastric-Type Cervical Adenocarcinoma: Phase 2 Trial (clinicaltrials.gov) - P2 | N=25 | Recruiting | Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology | Not yet recruiting ➔ Recruiting | Initiation date: Nov 2024 ➔ Feb 2025

Enrollment open • Trial initiation date • Cervical Adenocarcinoma • Cervical Cancer • Gastric Cancer • Oncology • Solid Tumor

Targeting Focal Adhesion Kinase in Lung Diseases: Current Progress and Future Directions. (PubMed, Biomolecules) - "Some have progressed to clinical trials (Defactinib (Phase II), PF-562271 (Phase I), CEP-37440 (Phase I), PND-1186 (Phase I), GSK-2256098 (Phase II), BI-853520 (Phase I)), offering potential therapeutic targets for lung diseases. Emerging methodologies, such as PROTAC degraders and combination regimens, demonstrate significant potential for future research. Based on a comprehensive analysis of the relevant literature from 2015 to the present, this review briefly introduces the structure and function of FAK and discusses recent research advancements regarding FAK and its inhibitors in the context of pulmonary diseases."

Journal • Review • Acute Lung Injury • Asthma • Colorectal Cancer • Gastric Cancer • Immunology • Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Targeted Protein Degradation

Ovarian Tumor FAK Inhibition Releases Omega-3 Fatty Acids Stimulating GATA6 Peritoneal Macrophage CXCL13 Production Enhancing Immunotherapy. (PubMed, bioRxiv) - "We show that focal adhesion kinase (FAK) inhibition with ifebemtinib or tumor genetic FAK knockout (KO) in syngeneic ovarian tumor models stimulated resident large peritoneal macrophages to express CXCL13 chemokine and promoted B cell infiltration. reveal that tumor FAK inhibition educates macrophages to express CXCL13 associated with B cell infiltration - highlighting a new therapeutic pathway linking FAK inhibition, omega-3 fatty acid containing exosomes, and macrophage mediated anti-tumor activation. Genetic or small molecule FAK inhibition enhances ovarian tumor B cell infiltrationTumor FAK inhibition stimulates GATA6+ macrophages to make CXCL13FAKi, pegylated doxorubicin and anti-TIGIT promote tertiary lymphoid structuresOmega-3 fatty acids stimulate human HGSOC ascites macrophages to make CXCL13."

IO biomarker • Journal • Gynecologic Cancers • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • CXCL13 • GATA6 • TIGIT

A Phase 3 Study of IN10018 in Combination With D-1553 Versus Standard Therapy for First Line Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation (clinicaltrials.gov) - P3 | N=400 | Not yet recruiting | Sponsor: InxMed (Shanghai) Co., Ltd.

New P3 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Sensitivity of Pancreatic Cancer Cell Lines to Clinically Approved FAK Inhibitors: Enhanced Cytotoxicity Through Combination with Oncolytic Coxsackievirus B3. (PubMed, Int J Mol Sci) - "In this study, we investigated the cytotoxicity of six FAKi (Defactinib, CEP-37440, VS-4718, VS-6062, Ifebemtinib and GSK2256098) used in clinical trials on five pancreatic tumor cell lines. Considering both oncolytic efficacy and the CI, the greatest enhancement in oncolytic activity was achieved when VS-4718 or CEP-37440 was combined with PD-H. These findings indicate that co-treatment with PD-H can potentiate the therapeutic activity of the selected FAKi and may represent a novel strategy to improve treatment outcomes in PDAC."

Journal • Preclinical • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

A Phase Ib Study of JMKX001899 in Combination With Other Therapies in Advanced NSCLC Harboring KRAS G12C Mutation (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: Jemincare | Not yet recruiting ➔ Recruiting

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

Targeting focal adhesion kinase to mitigate hepatotoxicity induced by PD-1 inhibition with or without KRAS G12C suppression. (ASCO 2025) - "FAK inhibition with Ifebe effectively reduces liver toxicity associated with KRAS G12C inhibition and PD-1 antibody therapy, underscoring the need for further clinical investigation."

IO biomarker • Hepatology • Oncology • KRAS

Safety and efficacy of ifebemtinib (IN10018) combined with garsorasib (D-1553) in KRAS G12C mutant solid tumors from a phase Ib/II study: Results from single-arm of non-small-cell lung cancer (NSCLC) and randomized part of colorectal cancer (CRC). (ASCO 2025) - P1/2 | "Combination of ifebe and D-1553, as a dual-oral regimen, is safe and highly efficacious against KRAS G12C mutant NSCLC with ORR over 90% and durable efficacy. Preliminary results from the randomized part of CRC demonstrated ORR doubling with the combo, validating the add-on benefits of ifebe. Our data suggest that ifebe could be an ideal partner of RASi."

Clinical • P1/2 data • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

InxMed Announces Promising Phase Ib/II Clinical Data for Ifebemtinib + KRAS G12C inhibitor in KRAS G12C-Mutant Solid Tumors at ASCO 2025 (The Manila Times) - P1/2 | N=92 | NCT05379946 | Sponsor: InventisBio Co., Ltd | P1b/2 | N=140 | NCT06166836 | Sponsor: InxMed (Shanghai) Co., Ltd. | "Key Highlights in First-line NSCLC: Dual-Oral Regimen Shows Durable Efficacy and Emerging Survival Benefit....Median progression-free survival (mPFS): 22.3 months; Median duration of response DOR (mDOR): 19.4 months; Median overall survival (mOS): not yet reached, with a significant uplifting and flattening survival curve indicating durable benefit. Key Findings in Previously Treated CRC: Randomized Trial Validates Synergy with KRAS G12Ci....ORR: 44.4% (combo) vs. 16.7% (mono); Disease control rate (DCR): 100.0% (combo) vs. 77.8% (mono); mPFS: 7.7 months (combo) vs. 4.0 months (mono); mOS: not yet reached in the combination arm; early separation observed in the survival curves."

P1/2 data • Colorectal Cancer • Non Small Cell Lung Cancer

IN10018-010: IN10018 Combination Therapy in Previously-treated Locally Advanced or Metastatic Solid Tumor Patients (clinicaltrials.gov) - P1/2 | N=68 | Completed | Sponsor: InxMed (Shanghai) Co., Ltd. | Active, not recruiting ➔ Completed | N=240 ➔ 68 | Trial primary completion date: Mar 2024 ➔ Aug 2024

Enrollment change • Platinum resistant • Platinum sensitive • Trial completion • Trial primary completion date • Breast Cancer • Head and Neck Cancer • Lung Cancer • Oncology • Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

IN10018 Combination Therapy in Previously-treated Solid Tumors (clinicaltrials.gov) - P1/2 | N=72 | Not yet recruiting | Sponsor: InxMed (Shanghai) Co., Ltd. | Trial completion date: Jul 2026 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Dec 2026

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

IN10018 in Combination With Standard Chemotherapy in High-grade Serous Epithelial Ovarian Cancer (clinicaltrials.gov) - P1/2 | N=150 | Recruiting | Sponsor: InxMed (Shanghai) Co., Ltd. | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Jun 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor

IN10018 in Combination With Pegylated Liposomal Doxorubicin (PLD) vs. Placebo in Combination With PLD for the Treatment of Platinum-resistant Recurrent Ovarian Cancer (clinicaltrials.gov) - P2 | N=168 | Recruiting | Sponsor: InxMed (Shanghai) Co., Ltd. | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2026

Platinum resistant • Trial completion date • Trial primary completion date • Oncology • Ovarian Cancer • Solid Tumor • MUC16

IN10018 Combination Therapy in Treatment-naïve ES-SCLC (clinicaltrials.gov) - P1/2 | N=120 | Recruiting | Sponsor: InxMed (Shanghai) Co., Ltd. | Trial primary completion date: Jan 2025 ➔ Dec 2025

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

A Phase Ib Study of JMKX001899 in Combination With Other Therapies in Advanced NSCLC Harboring KRAS G12C Mutation (clinicaltrials.gov) - P1 | N=72 | Not yet recruiting | Sponsor: Jemincare

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

Targeting FAK exhibits therapeutic effects on interstitial lung disease induced by trastuzumab deruxtecan (AACR 2025) - "Notably, we have now identified that FAK inhibition by the small molecule inhibitor Ifebemtinib (aka IN10018, Ifebe) can mitigate Enhertu-induced ILD. Collectively, the combination of FAK inhibition and Enhertu may offer improved therapeutic efficacy while mitigating ILD-related toxicities. These findings warrant further clinical investigation."

Oncology • Solid Tumor

Targeting FAK by Ifebemtinib synergizes with Pan RAS inhibitors in treating RAS mutant cancers (AACR 2025) - "Co-administration of a clinical-stage FAK inhibitor, Ifebemtinib (also known as Ifebe, IN10018), with RMC6236, a Pan-RAS inhibitor, exhibited synergistic cytotoxic effects in multiple RAS-mutant cancer cell lines. In summary, our study reveals that the combination of FAK inhibitor Ifebe with Pan-RAS inhibitor exhibits synergistic anti-cancer effects and further improves the outcomes of PD-1 blockade therapy. These preclinical results support the need for further clinical investigation."

IO biomarker • Oncology • KRAS • NRAS

Study to Evaluate D-1553 in Combination With IN10018 in Subjects With Solid Tumors (clinicaltrials.gov) - P1/2 | N=92 | Active, not recruiting | Sponsor: InventisBio Co., Ltd | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Targeting FAK improves the tumor uptake of antibody-drug conjugates to strengthen the anti-cancer responses. (PubMed, iScience) - "Antibody-drug conjugates (ADCs), exemplified by HER2-targeted Enhertu and TROP2-targeted Trodelvy, have demonstrated significant therapeutic potential in cancers. Combination therapy with IN10018 and ADCs targeting either HER2 or TROP2 consistently yielded superior antitumor outcomes compared to monotherapies in animal models. These findings provide compelling preclinical evidence supporting the clinical evaluation of IN10018 in combination with ADCs."

Journal • Fibrosis • Oncology • CAFs • HER-2

IN10018 tablets: New drug clinical trial approved, a ray of hope for patients with advanced cancer! [Google translation] (Sohu.com) - "On February 20, the drug 'IN10018 Tablets' of InsBio (Shanghai) Co., Ltd. obtained implicit clinical trial approval with the acceptance number of CXHL2401347. This news has attracted widespread attention, especially in the field of cancer treatment."

New trial • Oncology • Ovarian Cancer • Pancreatic Cancer

HX009+ IN10018 with or Without Standard Chemotherapy for Advanced Solid Tumours (clinicaltrials.gov) - P1/2 | N=124 | Recruiting | Sponsor: Hangzhou Hanx Biopharmaceuticals, Ltd. | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2027 ➔ Dec 2028 | Trial primary completion date: Dec 2025 ➔ Dec 2027

Enrollment open • Trial completion date • Trial primary completion date • Biliary Cancer • Biliary Tract Cancer • Melanoma • Oncology • Solid Tumor

IN10018 Monotherapy and Combination Therapy for Metastatic Melanoma (clinicaltrials.gov) - P1 | N=120 | Active, not recruiting | Sponsor: InxMed (Shanghai) Co., Ltd. | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2024 ➔ Dec 2025 | Trial primary completion date: Jun 2024 ➔ Jun 2025

Combination therapy • Enrollment closed • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor • NRAS

HX009+ IN10018 With or Without Standard Chemotherapy for Advanced Solid Tumours (clinicaltrials.gov) - P1/2 | N=124 | Not yet recruiting | Sponsor: Hangzhou Hanx Biopharmaceuticals, Ltd.

Metastases • New P1/2 trial • Biliary Cancer • Biliary Tract Cancer • Melanoma • Oncology • Solid Tumor

InxMed FAK Inhibitor Ifebemtinib Received Breakthrough Therapy Designation by China National Medical Products Administration for First-Line Non-Small Cell Lung Cancer (NSCLC) with KRAS G12C Mutation (PRNewswire) - "InxMed...announced that China National Medical Products Administration (NMPA) has granted Ifebemtinib (IN10018) Breakthrough Therapy designation (BTD) for the first-line (1L) treatment of non-small cell lung cancer (NSCLC) with KRAS G12C mutation in combination with garsorasib, a specific inhibitor of the KRAS G12C mutation. This is the second BTD ifebemtinib received....The BTD is supported by the data from the Phase Ib/II study evaluating the efficacy and safety of ifebemtinib in combination with garsorasib for the 1L treatment of NSCLC with KRAS G12C mutation (NCT06166836)....InxMed is currently conducting a registrational trial in platinum-resistant ovarian cancer in China, for which the company plans to submit a New Drug Application to the NMPA in 2025."

Breakthrough therapy • China filing • Evidence highlight • Non Small Cell Lung Cancer • Ovarian Cancer • KRAS

IN10018 with Nab-Paclitaxel and Cadonilimab for Metastatic or Recurrent Gastric-Type Cervical Adenocarcinoma: Phase 2 Trial (clinicaltrials.gov) - P2 | N=25 | Not yet recruiting | Sponsor: Wuhan Union Hospital, China

Metastases • New P2 trial • Cervical Cancer • Gastric Cancer • Oncology • Solid Tumor