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The addition of bemarituzumab to mFOLFOX6 (modified oxaliplatin, leucovorin, and fluorouracil) led to a statistically significant and clinically meaningful improvement in overall survival (OS) vs placebo plus chemotherapy in patients with HER2-negative, unresectable locally advanced or metastatic gastric or gastroesophageal junction (GEJ) cancer harboring FGFR2b overexpression, meeting the primary end point of the phase 3 FORTITUDE-101 trial (NCT05052801).¹

Findings announced by Amgen also showed that the most common treatment-emergent adverse effects (AEs) reported in more than 25% of patients treated in the bemarituzumab arm comprised reduced visual acuity, punctate keratitis, anemia, neutropenia, nausea, corneal epithelium defect, and dry eye. Although instances of ocular AEs were consistent with prior phase 2 data and occurred in both treatment arms, they were reported at a higher rate frequency and severity in the phase 3 bemarituzumab group.

Detailed data from the prespecified interim analysis will be presented at an upcoming medical meeting.

“Most patients with gastric cancer are diagnosed at an advanced stage, with poor prognosis, low survival rates, and limited therapeutic options,” Jay Bradner, MD, executive vice president of Research and Development at Amgen, stated in a news release. “These first positive topline results of an FGFR2b-targeted monoclonal antibody from our phase 3 FORTITUDE-101 study mark a meaningful advance in the development of effective targeted therapy for gastric cancer.”

FORTITUDE-101 Overview

The randomized, multicenter, double-blind, placebo-controlled trial enrolled patients at least 18 years of age with histologically documented locally advanced unresectable or metastatic gastric or GEJ cancer not amenable to curative therapy.² Patients needed to be positive for FGFR2b overexpression, defined 2+ or 3+ staining on at least 10% of tumor cells per centrally performed immunohistochemistry (IHC).

Other key inclusion criteria included an ECOG performance status of 0 or 1; evaluable disease that could be measurable or non-measurable per RECIST 1.1 criteria; no contraindications to mFOLFOX6; and adequate organ and bone marrow function.

Patients were excluded if they received prior treatment in the metastatic or unresectable setting; however, previous neoadjuvant, adjuvant, and perioperative therapy was permitted if completed more than 6 months prior to first dose of study treatment. Other exclusion criteria included any prior treatment with a selective FGFR inhibitor; HER2-positive disease; untreated or symptomatic central nervous system disease or brain metastases; and clinically significant cardiac disease.

A total of 547 patients enrolled across the study at 300 sites across 37 countries.¹ Patients were randomly assigned to receive bemarituzumab plus mFOLFOX6 or placebo plus mFOLFOX6.

Along with the primary end point of OS, secondary end points included progression-free survival, objective response rate, duration of response, disease control rate, quality of life, and safety.²

Bemarituzumab is also being investigated in the phase 3 FORTITUDE-102 study (NCT05111626), where patients with previously untreated gastric cancer are being randomly assigned to receive bemarituzumab in combination with chemotherapy and nivolumab (Opdivo) or placebo plus chemotherapy and nivolumab. Data from this study are expected to read out in the second half of 2025.¹

After the safety and tolerability of the combination of bemarituzumab, chemotherapy, and nivolumab were evaluated in the first nonrandomized part of the study, patients with locally advanced unresectable or metastatic, histologically documented gastric or GEJ adenocarcinoma are being randomly assigned between the 2 arms in the second part of the study. Notably, patients being enrolled to the randomized portion are required to have centrally confirmed FGFR2b overexpression per IHC.

References

1. Amgen announces positive topline phase 3 results for bemarituzumab in fibroblast growth factor receptor 2b (FGFR2b) positive first-line gastric cancer. News release. Amgen. June 30, 2025. Accessed June 30, 2025. https://www.amgen.com/newsroom/press-releases/2025/06/amgen-announces-positive-topline-phase-3-results-for-bemarituzumab-in-fibroblast-growth-factor-receptor-2b-fgfr2b-positive-firstline-gastric-cancer
2. Bemarituzumab or placebo plus chemotherapy in gastric cancers with fibroblast growth factor receptor 2b (FGFR2b) overexpression (FORTITUDE-101). ClinicalTrials.gov. Updated February 7, 2025. Accessed June 30, 2025. https://clinicaltrials.gov/study/NCT05052801
3. Bemarituzumab plus chemotherapy and nivolumab versus chemotherapy and nivolumab for FGFR2b overexpressed untreated advanced gastric and gastroesophageal junction cancer. (FORTITUDE-102). ClinicalTrials.gov. Updated June 12, 2025. Accessed June 30, 2025. https://clinicaltrials.gov/study/NCT05111626

Patients with obesity who received maridebart cafraglutide (MariTide; Amgen), a once-monthly obesity medication, demonstrated weight loss of up to 19.9% in a phase 2 trial (NCT05669599).¹ Those with obesity and type 2 diabetes showed weight loss of up to 17%.

Maridebart cafraglutide is a long-acting peptide–antibody conjugate that combines glucagon-like peptide-1 (GLP-1) receptor agonism and glucose-dependent insulinotropic polypeptide (GIP) receptor antagonism. The 2 identical GLP-1 peptide analogs conjugated to a single monoclonal antibody antagonist to the GIP receptor result in a 21-day half-life, 3 times longer than the FDA approved longest-acting once-weekly anti-obesity medication, semaglutide. The extended half-life can potentially lead to increased access and adherence for those whose health and access to health care are disproportionately affected by socioeconomic status.² 

“[Maridebart cafraglutide]’s monthly or less frequent dosing has the potential to improve adherence and long-term weight control, providing the opportunity to optimize health outcomes for people living with obesity, type 2 diabetes, and related conditions,” Jay Bradner, MD, executive vice president of Research and Development at Amgen, said in a press release.³ “[Maridebart cafraglutide] delivered strong efficacy, including sustained weight loss without a plateau in the 52-week phase 2 study and meaningful improvements in cardiometabolic risk factors, representing a defining advance for the obesity field.”

Phase 2 of the trial tested the efficacy, adverse event profile, and safety of maridebart cafraglutide at various doses with and without escalation.¹ The study enrolled 592 participants—465 in the obesity cohort and 127 in the obesity-diabetes cohort. The obesity cohort was randomly assigned in a 3:3:3:2:2:2:3 ratio to receive either 52 weeks of maridebart cafraglutide subcutaneously at 140, 280, or 420 mg every 4 weeks without dose escalation; 420 mg every 8 weeks without dose escalation; 420 mg every 4 weeks with either a 4- or 12-week dose escalation; or a placebo. Participants in the obesity-diabetes cohort were randomly assigned in a 1:1:1:1 ratio to receive maridebart cafraglutide over 52 weeks at a dosage of 140, 280, or 420 mg every 4 weeks or a placebo.

The mean percent change in body weight from the obesity cohort from baseline to 52 weeks ranged from −12.3% to −16.2% (95% CI, −15.0 to −9.7) to −16.2% (95% CI, −18.9 to −13.5). The obesity-diabetes cohort mean percent change in body weight ranged from −8.46% (95% CI, −11.0 to −5.7) to −12.3% (95% CI, −15.3 to −9.2).

Those in both cohorts who received maridebart cafraglutide also showed a significant difference in the percentage points of glycated hemoglobin (HbA1c) levels when analyzed using the treatment policy estimand. The obesity cohort had a mean difference of –0.32 (95% CI, –0.5 to –0.2) percentage points measuring glycated hemoglobin levels. Similarly, the obesity-diabetes cohort showed a mean difference of –1.43 (95% CI, –1.9 to –0.7) percentage points in glycated hemoglobin. When analyzed using the efficacy demand, the obesity cohort did not show a significant difference in weight loss; however, the obesity-diabetes cohort did, with –2.03 (95% CI, –2.4 to –1.6) percentage points.

Participants in both cohorts experienced improvement in additional secondary end points, including differences in systolic and diastolic blood pressure, high-sensitivity C-reactive protein (hs-CRP), and select lipid variables. Furthermore, those receiving a dose escalation over 4 or 12 weeks did not show significant differences in primary or secondary end points when compared with those that did not receive dose escalation.

Adverse events occurred in an average of 93.5% of participants across both cohorts. The most common adverse events (AEs) were gastrointestinal, which included mild to moderate nausea, vomiting, constipation, retching, and diarrhea. There was a lower incidence of adverse events in the groups with dose escalation and those starting at a lower dose across both cohorts.

Of the 592 participants in the obesity cohort, 8% in the dose escalation group discontinued the trial due to GI AEs, as opposed to the 12% to 17% in the no–dose escalation groups. Similarly, 6% to 16% of participants in the obesity-diabetes cohort discontinued due to GI-related adverse events. Other predefined adverse events varied in severity, ranging from mild to moderate, and included injection-site rash, reactions, and/or urticaria.

“These results, alongside the phase 1 pharmacokinetics low-dose initiation data, have shaped our phase 3 MARITIME program,” Bradner said.³

References

1. Jastreboff AM, Ryan DH, Bays HE, et al. Once-monthly maridebartcafraglutide for the treatment of obesity — a phase 2 trial. New England Journal of Medicine. Published online June 23, 2025. doi:10.1056/nejmoa2504214
2. Eberly LA, Yang L, Essien UR, et al. Racial, ethnic, and socioeconomic inequities in glucagon-like peptide-1 receptor agonist use among patients with diabetes in the US. JAMA Health Forum. 2021;2(12): e214182. doi:10.1001/jamahealthforum.2021.4182
3. Results from Amgen’s phase 2 obesity study of monthly maritide presented at the American Diabetes Association 85th Scientific Sessions. Amgen. June 23, 2025. Accessed June 25, 2025. https://www.amgen.com/newsroom/press-releases/2025/06/results-from-amgens-phase-2-obesity-study-of-monthly-maritide-presented-at-the-american-diabetes-association-85th-scientific-sessions