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

Update on Amgen’s bemarituzumab Phase 3 FORTITUDE-101 Study (Zai Lab Press Release) - "At the pre-specified interim analysis, which was the primary analysis, the bemarituzumab plus chemotherapy regimen demonstrated a clinical and statistically significant improvement in overall survival (OS) compared to chemotherapy alone. However, at the final analysis, the magnitude of the previously observed survival benefit has attenuated. Amgen has indicated that the results from both the interim analysis and final analysis will be presented at an upcoming major medical meeting....Data readout from FORTITUDE-102 is anticipated by the end of 2025 or the first half of 2026."

P3 data • Gastric Cancer

Evaluating the Impact of Monoclonal Antibodies on Survival Outcomes in Advanced Gastric Cancer: A Systematic Review of RCTs (ACG 2025) - "Pembrolizumab plus chemotherapy also significantly enhances survival outcomes. In Boku et al., 2021, nivolumab demonstrated a significant OS benefit over placebo (5.3 vs 4.1 months) and a modest PFS benefit (1.61 vs 1.45 months). In Kong et al., 2024, inetetamab improved PFS compared to trastuzumab (8.5 vs 7.3 months, P = 0.046), but OS (15.4 vs 14.3 months) was not significantly different. Kang et al., 2024 reported that bemarituzumab plus mFOLFOX6 significantly improved both PFS (12.9 vs 8.2 months) and OS (24.7 vs 12.9 months) compared to placebo."

Metastases • Review • Gastric Cancer • Oncology • Solid Tumor

ANGELICA: AssociatiNG Bevacizumab bEmarituzumab for GynecoLogIcal CAncer (clinicaltrials.gov) - P1/2 | N=87 | Not yet recruiting | Sponsor: Centre Leon Berard

dMMR • New P1/2 trial • pMMR • Cervical Cancer • Endometrial Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

WJOG18524G: A Single-arm Phase 2 Study Evaluating Bemarituzumab Combined with Ramucirumab and Paclitaxel in FGFR2b-positive Advanced Gastric or Gastroesophageal Junction Cancer (RAINBIRD) (ESMO 2025) - No abstract available

Metastases • P2 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

A Phase II Clinical Trial Evaluating the Efficacy and Safety of Bemarituzumab in Combination with Anlotinib as Consolidation Therapy in Limited-Stage Small Cell Lung Cancer (LS-SCLC) Patients Without Progression After Definitive Treatment (L-STAR Study) (ChiCTR) - P2 | N=35 | Not yet recruiting | Sponsor: Shandong First Medical University Affiliated Cancer Hospital; Shandong First Medical University Affiliated Cancer Hospital

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

FORTITUDE-103: A Study Evaluating Bemarituzumab in Combination With Other Anti-cancer Therapies in Subjects With Previously Untreated Advanced Gastric or Gastroesophageal Junction Cancer. (clinicaltrials.gov) - P1/2 | N=70 | Recruiting | Sponsor: Amgen | Trial completion date: Apr 2028 ➔ Aug 2028 | Trial primary completion date: Mar 2026 ➔ Jun 2026

Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Oncology • Solid Tumor

Zai Lab Announces Second Quarter 2025 Financial Results and Recent Corporate Updates (Businesswire) - "Upcoming Potential NMPA Submissions: Bemarituzumab (FGFR2b) in first-line gastric cancer in the second half of 2025. Upcoming Potential NMPA Approvals: Tisotumab Vedotin (Tissue Factor ADC) in recurrent or metastatic cervical cancer following progression on or after chemotherapy; Repotrectinib (ROS1/TRK) in NTRK+ solid tumors."

China approval • China filing • Cervical Cancer • Gastric Cancer • Solid Tumor

Bemarituzumab: Data readout from P3 FORTITUDE-102 trial (NCT05111626) for 1L gastric/GEJ cancer in H2 2025/H1 2026 (Amgen) - Q2 2025 Results

P3 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology

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 | Trial completion date: Sep 2027 ➔ Feb 2026

Monotherapy • Pan tumor • Platinum resistant • Trial completion date • 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

FORTITUDE-101: Bemarituzumab or Placebo Plus Chemotherapy in Gastric Cancers With Fibroblast Growth Factor Receptor 2b (FGFR2b) Overexpression (clinicaltrials.gov) - P3 | N=547 | Active, not recruiting | Sponsor: Amgen | Trial completion date: Aug 2025 ➔ Jun 2026

Trial completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • FGFR2

FGFR2b protein overexpression: An emerging biomarker in gastric and gastroesophageal junction adenocarcinoma. (PubMed, Cancer Treat Rev) - "Fibroblast growth factor receptor 2 isoform IIIb (FGFR2b) is an emerging biomarker under phase 3 clinical investigation for G/GEJC with the novel monoclonal antibody bemarituzumab. FGFR2b protein overexpression in gastric cancer, together with its function in various oncogenic signaling pathways, makes it an attractive target for precision medicine and thereby has gained clinical interest for its potential prognostic role in G/GEJC. Thus, to explore the potential role of FGFR2b, this narrative review summarizes the role and mechanism of FGFR2b in advanced G/GEJC, describes appropriate detection methodology for FGFR2b protein overexpression, and discusses future considerations for precision treatment in advanced G/GEJC with respect to FGFR2b protein overexpression and the emergence of other biomarkers."

Biomarker • Journal • Review • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • FGFR2

AMGEN ANNOUNCES POSITIVE TOPLINE PHASE 3 RESULTS FOR BEMARITUZUMAB IN FIBROBLAST GROWTH FACTOR RECEPTOR 2b (FGFR2b) POSITIVE FIRST-LINE GASTRIC CANCER (Amgen Press Release) - P3 | N=547 | FORTITUDE-101 (NCT05052801) | Sponsor: Amgen | "Amgen...announced the Phase 3 FORTITUDE-101 clinical trial evaluating first-line bemarituzumab plus chemotherapy (mFOLFOX6) met its primary endpoint of overall survival (OS) at a pre-specified interim analysis. Bemarituzumab plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in OS as compared to placebo plus chemotherapy in people living with unresectable locally advanced or metastatic gastric or gastroesophageal junction (G/GEJ) cancer with FGFR2b overexpression and who are non-HER2 positive....Detailed results from the trial will be shared at a future medical meeting....A Phase 3 study of bemarituzumab plus chemotherapy and nivolumab is also ongoing in patients with first-line gastric cancer, with a data readout anticipated in H2 2025."

P3 data: top line • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma

Clinical characterization of FGFR2b expression in patients with advanced gastric or gastroesophageal junction adenocarcinoma. (PubMed, ESMO Open) - "This study revealed limited overlap of FGFR2b overexpression with currently actionable biomarkers, suggesting FGFR2b is a novel biomarker that identifies a distinct GC/GEJC patient population who may benefit most from an FGFR2b-targeting therapy."

IO biomarker • Journal • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • CLDN18 • FGFR2 • HER-2 • PD-L1

FORTITUDE-102: Bemarituzumab Plus Chemotherapy and Nivolumab Versus Chemotherapy and Nivolumab for FGFR2b Overexpressed Untreated Advanced Gastric and Gastroesophageal Junction Cancer. (clinicaltrials.gov) - P3 | N=515 | Active, not recruiting | Sponsor: Amgen | Trial completion date: Sep 2026 ➔ Jan 2027 | Trial primary completion date: Sep 2026 ➔ Jan 2026

Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • FGFR2

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