bemarituzumab (AMG 552) / ZAI Lab, Amgen - LARVOL DELTA

Advancing Ocular Safety Profile Assessment: A Novel Grading Scale for Ocular Adverse Reactions Associated with Bemarituzumab. (PubMed, Ophthalmol Ther) - "Fibroblast growth factor receptors (FGFRs), expressed across various parts of the eye, can become unintended targets of FGFR inhibitors such as erdafitinib, infigratinib, and pemigatinib, leading to ocular adverse events (AEs) affecting the ocular surface and retina. This grading scale is being used across the clinical development program for bemarituzumab to precisely characterize the ocular safety profile, enabling cross-specialty collaboration between oncologists and eye care providers to implement appropriate management strategies. This commentary article highlights the efforts led by Amgen in collaboration with regulatory, medical, and academic fields to develop tools that facilitate early recognition of adverse reactions and appropriate interventions for patient care."

Journal • Oncology • Ophthalmology

NeoBEMA: Peri-operative Treatment of Resectable Gastroesophageal Cancer Using Bemarituzumab (BEMA) Plus Perioperative Treatment (clinicaltrials.gov) - P1 | N=27 | Not yet recruiting | Sponsor: European Organisation for Research and Treatment of Cancer - EORTC

New P1 trial • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Oncology • Solid Tumor

FORTITUDE-301: A Study Evaluating Bemarituzumab in Solid Tumors With Fibroblast Growth Factor Receptor 2b (FGFR2b) Overexpression (clinicaltrials.gov) - P1/2 | N=260 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting

Enrollment closed • Monotherapy • Pan tumor • Breast Cancer • Cholangiocarcinoma • Endometrial Cancer • Head and Neck Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

BEMAFLOT: Open-label Non-randomized Multicentric Phase 2 Study Evaluating the Combination of Bemarituzumab + FLOT Chemotherapy in Perioperative Setting for Resectable Stage cT2-T4a or N+ Gastric and GEJ Adenocarcinoma Overexpressing FGFR2b (clinicaltrials.gov) - P2 | N=49 | Not yet recruiting | Sponsor: Institut Cancerologie de l'Ouest

New P2 trial • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology

ALK201, a first-in-class FGFR2b-targeting antibody-drug conjugate for patients with FGFR2b+ gastric cancer and other solid tumors (AACR 2025) - P1/2 | "ALK201 blocked FGF7/10-FGFR2b interaction and inhibited downstream phospho-ERK activation, comparable to Bemarituzumab. In summary, preclinical results indicated that ALK201 is an effective candidate for the treatment of solid tumors expressing FGFR2b with a tolerable safety profile. The phase I/II clinical study including dose escalation and dose expansion to evaluate the safety, tolerability, PK and anti-tumor activity of ALK201 in adult participates with advanced solid tumor is ongoing (NCT06656390)."

Clinical • Late-breaking abstract • Gastric Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • FGF7 • FGFR2

Characterization of novel humanized FGFR2b antibody-based ADCs site-specifically conjugated with topoisomerase I inhibitor payload in preclinical tumor models (AACR 2025) - "Anti-tumor efficacy was evaluated in FGFR2b-positive tumor cell line-derived xenograft (CDX) models in mice. 38D4 specifically binds to FGFR2b with a higher affinity than the Bemarituzumab-analog. FGFR2b ADC TST105 demonstrated the high potency, strong anti-tumor activity and bystander effect in the preclinical studies, which support further investigations of TST105 in FGFR2b positive solid tumors."

Preclinical • Biliary Cancer • Cholangiocarcinoma • Colorectal Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • FGFR2

Carboplatin/Cisplatin + Etoposide + Benmelstobart Sequential Benmelstobart Combined With Anlotinib Versus Carboplatin/Cisplatin + Etoposide + Tislelizumab Sequential Tislelizumab in the Treatment of Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=134 | Recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Not yet recruiting ➔ Recruiting

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

SCR-A002, a novel FGFR2b-targeting ADC for solid tumors (AACR 2025) - "SCR-A002 showed remarkable anti-tumor efficacy in preclinical data, suggesting that SCR-A002 is expected to provide a new treatment option as single agent or combo with SoC for patients with FGFR2b-overexpressing solid tumor."

Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • FGFR2

Preclinical evaluation of BG-C137, a potential first-in-class FGFR2b-targeting ADC, for the treatment of FGFR2b-expressing cancer (AACR 2025) - P1 | "Indeed, the clinical benefit of targeting FGFR2b has been demonstrated by Bemarituzumab, an Fc-enhanced monoclonal antibody in combination with chemotherapy in first-line FGFR2b-expressing gastric cancer. With its differentiated targeting strategy, BG-C137 is not only a first-in-class FGFR2b ADC but also holds the potential to pursue the best-in-class opportunity in FGFR2b targeting treatments. Together, these observations support the clinical development of BG-C137 for the treatment of FGFR2b-expressing tumors (ClinicalTrials.gov ID NCT06625593)."

Preclinical • Gastric Cancer • Oncology • Solid Tumor • FGFR2

Low positivity rate of fibroblast growth factor receptor 2b is associated with heterogeneous expression in gastric cancer. (PubMed, Gastric Cancer) - "Significant intratumoral and intrapatient heterogeneity is observed in FGFR2b overexpression. Given this variability in expression levels, a single endoscopic biopsy may not accurately assess FGFR2b overexpression. The FGFR2b positivity rate in gastric cancers was 4.1%, likely due to the substantial heterogeneity in its expression."

Heterogeneity • Journal • Gastric Cancer • Oncology • Solid Tumor • FGFR2

Carboplatin/Cisplatin + Etoposide + Benmelstobart Sequential Benmelstobart Combined With Anlotinib Versus Carboplatin/Cisplatin + Etoposide + Tislelizumab Sequential Tislelizumab in the Treatment of Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=134 | Not yet recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

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

Zai Lab Announces Fourth Quarter and Full Year 2024 Financial Results and Recent Corporate Updates (Businesswire) - "Tisotumab Vedotin (Tissue Factor ADC): BLA submission in recurrent or metastatic cervical cancer following progression on or after chemotherapy in the first quarter of 2025. Bemarituzumab (FGFR2b): BLA submission in first-line gastric cancer in the first half of 2025. Repotrectinib (ROS1/TRK): supplementary NDA submission in NTRK+ solid tumors in the first half of 2025. Tumor Treating Fields (TTFields): Marketing Authorization Application submissions in second-line+ NSCLC following progression on or after platinum-based chemotherapy and in first-line pancreatic cancer...Second-Line+ Extensive-Stage SCLC (ES-SCLC): Zai Lab to present updated data at a major medical conference in the first half of 2025. Zai Lab plans to initiate a pivotal study in 2025...Other neuroendocrine tumors: Zai Lab to initiate a global Phase 1 study in the first half of 2025...ZL-6201 (LRRC15 ADC): Zai Lab to provide preclinical data update and initiate a global Phase 1 study in sarcoma."

China filing • Clinical data • New P1 trial • Preclinical • Cervical Cancer • Gastric Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Sarcoma • Small Cell Lung Cancer • Solid Tumor

Bemarituzumab in FGFR2b+ Patients with Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction, Who Failed At Least One Prior Line of Palliative Chemotherapy (clinicaltrials.gov) - P2 | N=126 | Recruiting | Sponsor: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Not yet recruiting ➔ Recruiting | Initiation date: Dec 2024 ➔ Mar 2025

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

First-line Bemarituzumab + SOX + Nivolumab for Advanced G/GEJC with FGFR2b Overexpression: FORTITUDE-103 Phase 2 Design (JSMO 2025) - No abstract available

Clinical • Metastases • P2 data • Oncology

FORTITUDE-301: A Study Evaluating Bemarituzumab in Solid Tumors With Fibroblast Growth Factor Receptor 2b (FGFR2b) Overexpression (clinicaltrials.gov) - P1/2 | N=303 | Recruiting | Sponsor: Amgen | Trial completion date: Dec 2027 ➔ Sep 2027 | Trial primary completion date: Mar 2026 ➔ Dec 2025

Monotherapy • Pan tumor • Trial completion date • Trial primary completion date • Breast Cancer • Cholangiocarcinoma • Endometrial Cancer • Head and Neck Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

Community Register of orphan medicinal products (European Commission) - Product name: ACTIVEEU/3/24/2966, Designation number: EU/3/24/2966, Active substance: Bemarituzumab, Indication: Treatment of gastric cancer - 22 Aug 2024 - Orphan designation - EMA/OD/0000171163 - (2024)6002 of 21 Aug 2024

Orphan drug • Gastric Cancer

Fourth Quarter Product and Pipeline Update…Bemarituzumab (PRNewswire) - "FORTITUDE-101, a Phase 3 study of bemarituzumab plus chemotherapy, is ongoing in patients with first-line gastric cancer. Data readout is anticipated in H1 2025. FORTITUDE-102, a Phase 1b/3 study of bemarituzumab plus chemotherapy and nivolumab is ongoing in patients with first-line gastric cancer. Phase 3 data readout is anticipated in H2 2025."

P3 data • Trial status • Gastric Cancer

FORTITUDE-301: A Study Evaluating Bemarituzumab in Solid Tumors With Fibroblast Growth Factor Receptor 2b (FGFR2b) Overexpression (clinicaltrials.gov) - P1/2 | N=303 | Recruiting | Sponsor: Amgen | Trial completion date: Jul 2027 ➔ Dec 2027 | Trial primary completion date: Oct 2025 ➔ Mar 2026

Monotherapy • Trial completion date • Trial primary completion date • Breast Cancer • Cholangiocarcinoma • Endometrial Cancer • Head and Neck Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

Bemarituzumab: Regulatory submission in China for 1L gastric cancer in 2025 (Zai Lab, 43rd Annual J.P. Morgan Healthcare Conference)

China filing • Gastric Cancer • Oncology • Solid Tumor

Bemarituzumab: Regulatory submission in China for 1L gastric cancer in 2025 (Zai Lab, 43rd Annual J.P. Morgan Healthcare Conference)

China filing • Gastric Cancer • Oncology • Solid Tumor

Bemarituzumab: Data readout from P3 FORTITUDE-101 trial (NCT05052801) for 1L gastric/GEJ cancer in H1 2025 (Amgen, 43rd Annual J.P. Morgan Healthcare Conference) - Data readout from P3 FORTITUDE-102 trial (NCT05111626) for 1L gastric/GEJ cancer in H2 2025

P3 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

Bemarituzumab: Data readout from P3 FORTITUDE-101 trial (NCT05052801) for 1L gastric/GEJ cancer in H1 2025 (Amgen, 43rd Annual J.P. Morgan Healthcare Conference) - Data readout from P3 FORTITUDE-102 trial (NCT05111626) for 1L gastric/GEJ cancer in H2 2025

P3 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

Systematic Literature Review (SLR) of Randomized Controlled Trials (RCTs) of Treatments for First-Line (1L) Gastric Cancer/Gastroesophageal Junction Adenocarcinoma (GC/GEJ) in Adult Patients (ISPOR-EU 2024) - "Among trials of PD-1/PD-L1 inhibitors (tislelizumab, nivolumab, pembrolizumab, sugemalimab, sintilimab), improvements in overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were observed for PD-1/PD-L1 inhibitors plus chemotherapy versus chemotherapy alone at median follow-up times ranging from 11.6 to 54.3 months, with median OS, median PFS, and ORR ranging from 12.5 to 17.45 months, 6.9 to 10.94 months, and 47.3% to 68.6%, respectively...Among other targeted therapies, response and survival benefits compared to chemotherapy were mixed; improvements in response and survival were seen with the CLDN18.2 inhibitor zolbetuximab and the FGFR inhibitor bemarituzumab, while benefits compared to chemotherapy were not seen with cetuximab, ramucirumab, andecaliximab, onartuzumab, rilotumumab, pazopanib, or ipatasertib... PD-1/PD-L1 inhibitors showed improved efficacy compared to chemotherapy for the treatment of 1L GC/GEJ; while other..."

Clinical • IO biomarker • Review • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • CLDN18 • CTLA4 • HER-2

A Study of Bemarituzumab Monotherapy and Combination With Other Anti-cancer Therapy in SqNSCLC With FGFR2b Overexpression (FORTITUDE-201) (clinicaltrials.gov) - P1 | N=74 | Terminated | Sponsor: Amgen | Completed ➔ Terminated; Business decision not due to safety concerns

Monotherapy • Trial termination • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • NTRK

Community Register of orphan medicinal products (European Commission) - Product name: ACTIVEEU/3/24/2966, Designation number: EU/3/24/2966, Active substance: Bemarituzumab, Indication: Treatment of gastric cancer. 22 Aug 2024 - Orphan designation - EMA/OD/0000171163 - (2024)6002 of 21 Aug 2024

Orphan drug • Gastric Cancer