Bemarituzumab for Solid Cancers

(FORTITUDE-301 Trial)

Not currently recruiting at 185 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Amgen

Must not be taking: Anti-arrhythmics, Ophthalmic steroids

Disqualifiers: CNS metastases, Cardiac disease, Ophthalmologic disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of a new drug, bemarituzumab, for treating certain solid cancers. It focuses on cancers that have relapsed or become resistant to treatment and show a specific marker called FGFR2b. Participants should have a type of cancer, such as head and neck, triple-negative breast, or lung adenocarcinoma, which has progressed despite previous treatments. The study aims to determine the best dose and assess whether the drug can shrink tumors. As a Phase 1 trial, the research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that bemarituzumab is likely to be safe for humans?

Research shows that bemarituzumab has a manageable safety profile. Studies have found it is generally well-tolerated with standard chemotherapy drugs. For example, one study found that patients who received bemarituzumab with chemotherapy responded well and experienced manageable side effects.

Early results also suggest that bemarituzumab alone, without other drugs, is tolerable for patients with certain cancers. While side effects can occur, they are usually manageable and not severe, allowing many patients to undergo treatment without major issues.

Since this study is in its early stages, it focuses heavily on safety. Researchers closely monitor how patients react to the drug. So far, the results are promising for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about bemarituzumab because, unlike existing treatments for solid tumors, it specifically targets FGFR2b overexpression, a marker found in certain aggressive cancers. This precision targeting could mean more effective treatment with fewer side effects compared to broad-spectrum chemotherapy, which often affects healthy cells too. Additionally, bemarituzumab has the potential to treat relapsed or refractory cases where standard therapies have failed, offering hope for patients with limited options.

What evidence suggests that bemarituzumab might be an effective treatment for solid cancers?

Research shows that bemarituzumab targets FGFR2b, a protein found in many solid tumors. Studies have demonstrated that it can slow tumor growth by blocking this protein. One study revealed that patients with FGFR2b-positive stomach cancer who received bemarituzumab had a median progression-free survival of 9.5 months. Their tumors took longer to grow or spread compared to those who didn't receive the treatment. In this trial, participants will receive bemarituzumab in two parts: Part 1 will explore different dose regimens, and Part 2 will expand on the recommended Phase 2 dose identified in Part 1. Early trials also indicate that it can stop tumor cells from dividing, which is a promising sign for treating cancers with FGFR2b. ^{4 5 6 7 8}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

Adults with certain advanced solid tumors that have grown or returned after treatment can join this trial. They must have tried at least one standard therapy, be in good physical condition (ECOG 0-1), and their tumor must show high levels of FGFR2b protein. People with untreated brain metastases, significant heart issues, eye problems requiring steroids, or those who've had recent corneal surgery cannot participate.

Inclusion Criteria

I am at least 18 years old or considered an adult in my country.

I am aware of all approved treatments for my cancer before considering bemarituzumab.

My tumor has high levels of FGFR2b.

Exclusion Criteria

I have brain metastases or leptomeningeal disease that is either untreated or causing symptoms.

I have recent or worsening eye problems.

I have not been treated with experimental drugs targeting the FGF pathway, unless it's a standard treatment for my cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Part 1: Monotherapy Dose Exploration

Participants receive 1 of 2 dose regimens of bemarituzumab to determine recommended Phase 2 dose

Up to 2 years

Treatment - Part 2: Monotherapy Dose Expansion

Participants receive the dose of bemarituzumab identified as the recommended Phase 2 dose during Part 1

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bemarituzumab

Trial Overview

The study is testing the safety and potential cancer-fighting ability of a drug called Bemarituzumab in patients whose tumors overexpress FGFR2b. It's for those who've already undergone other treatments without success.

How Is the Trial Designed?

Group I: Part 2: Monotherapy Dose Expansion Experimental Treatment 1 Intervention

Participants across multiple primary epithelial solid tumors with centrally determined FGFR2b overexpression and relapsed/refractory unresectable and/or metastatic disease will receive the dose of bemarituzumab identified as the recommended Phase 2 dose during Part 1.

Group II: Part 1: Monotherapy Dose Exploration Experimental Treatment 1 Intervention

Participants across multiple primary epithelial solid tumors with centrally determined FGFR2b overexpression and relapsed/refractory unresectable and/or metastatic disease will receive 1 of 2 dose regimens of bemarituzumab to determine recommended Phase 2 dose.

Who Is Running the Clinical Trial?

Amgen

Lead Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Published Research Related to This Trial

A population pharmacokinetic analysis of bemarituzumab, involving 1552 serum samples from 173 patients, revealed that the drug follows a two-compartment model with both linear and nonlinear elimination, indicating a well-defined pharmacokinetic profile.

The study found that factors like body weight and gender had minimal effects on the drug's exposure, suggesting that no dose adjustments are necessary for future phase 3 trials in patients with FGFR2b overexpression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Covariate effects and population pharmacokinetic analysis of the anti-FGFR2b antibody bemarituzumab in patients from phase 1 to phase 2 trials. Xiang, H., Liu, L., Gao, Y., et al.[2022]

The pharmacokinetics of bemarituzumab, an anti-fibroblast growth factor receptor 2b antibody, were analyzed using a two-compartment model, revealing that factors like albumin, gender, and body weight influence its clearance, but no dose adjustments are necessary.

A dosing regimen of 15 mg/kg every 2 weeks, with an initial dose of 7.5 mg/kg, is projected to achieve the desired drug concentration in over 95% of patients, which was confirmed in the phase 1 FIGHT trial, supporting its use in treating gastric and gastroesophageal junction adenocarcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic analysis of phase 1 bemarituzumab data to support phase 2 gastroesophageal adenocarcinoma FIGHT trial. Xiang, H., Liu, L., Gao, Y., et al.[2021]

The FIGHT trial is a Phase III study evaluating bemarituzumab, a monoclonal antibody targeting FGFR2b, in patients with untreated advanced gastroesophageal cancer, focusing on those whose tumors overexpress FGFR2b.

The trial aims to determine the efficacy of bemarituzumab combined with mFOLFOX6 chemotherapy compared to mFOLFOX6 with a placebo, with overall survival as the primary endpoint and safety as a key secondary endpoint.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bemarituzumab with modified FOLFOX6 for advanced FGFR2-positive gastroesophageal cancer: FIGHT Phase III study design. Catenacci, DV., Tesfaye, A., Tejani, M., et al.[2019]

Bemarituzumab was found to be well tolerated in a phase I trial with 79 patients, with no dose-limiting toxicities and a recommended dose of 15 mg/kg every 2 weeks, indicating a favorable safety profile.

In patients with high FGFR2b-overexpressing gastric and gastroesophageal junction adenocarcinoma, bemarituzumab showed preliminary efficacy, with 17.9% achieving a confirmed partial response, suggesting potential as a treatment option in advanced stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Escalation and Expansion Study of Bemarituzumab (FPA144) in Patients With Advanced Solid Tumors and FGFR2b-Selected Gastroesophageal Adenocarcinoma. Catenacci, DVT., Rasco, D., Lee, J., et al.[2021]

Pembrolizumab was found to be safe and well tolerated in a phase I study involving 20 patients with advanced solid tumors, with no dose-limiting toxicities observed at doses up to 10 mg/kg every 2 weeks.

The treatment demonstrated durable antitumor activity, with complete responses in two patients and stable disease in 15 others, indicating that a minimum effective dose for antitumor activity is 2 mg/kg every 3 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Pembrolizumab (MK-3475; Anti-PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors. Patnaik, A., Kang, SP., Rasco, D., et al.[2022]

Bemarituzumab is a novel monoclonal antibody that targets FGFR2b, showing strong potential as a cancer treatment by inhibiting tumor growth through two mechanisms: blocking FGFR2b signaling and enhancing immune cell activity against tumors.

In preclinical studies, bemarituzumab demonstrated significant anti-tumor effects both alone and in combination with chemotherapy or anti-PD-1 therapy, while showing a favorable safety profile in toxicity studies, supporting its advancement to clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical characterization of bemarituzumab, an anti-FGFR2b antibody for the treatment of cancer. Xiang, H., Chan, AG., Ahene, A., et al.[2022]

In a phase 2 trial involving 155 patients with advanced gastric or gastro-oesophageal junction adenocarcinoma, bemarituzumab combined with mFOLFOX6 showed a median progression-free survival of 9.5 months compared to 7.4 months for the placebo group, indicating potential efficacy despite not reaching statistical significance.

The treatment was associated with a higher incidence of corneal disorders and treatment-related deaths, highlighting the need for careful monitoring of safety, particularly regarding ocular side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bemarituzumab in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma (FIGHT): a randomised, double-blind, placebo-controlled, phase 2 study. Wainberg, ZA., Enzinger, PC., Kang, YK., et al.[2023]

Citations

1.

clinicaltrial.be

clinicaltrial.be/en/details/29798?only_active=0&only_eligible=0&only_recruiting=0&per_page=20

A Study Evaluating Bemarituzumab in Solid Tumors With ...

Participants across multiple primary epithelial solid tumors with centrally determined FGFR2b overexpression and relapsed/refractory ...

2.

empr.com

empr.com/news/investigational-therapy-improves-overall-survival-in-fgfr2b-positive-gastric-cancer/

Investigational Therapy Improves Overall Survival in ...

Bemarituzumab is an investigational treatment that targets FGFR2b, which has been found to be overexpressed in approximately 30% of patients ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05325866

A Study Evaluating Bemarituzumab in Solid Tumors With ...

... Efficacy of Bemarituzumab Monotherapy in Solid Tumors With FGFR2b Overexpression (FORTITUDE-301) ... Other solid tumor cohort excludes primary tumors of ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11016503/

Bemarituzumab as first-line treatment for locally advanced or ...

The primary analysis (median follow-up, 10.9 months) showed that the median progression-free survival (PFS) was 9.5 months (95% CI 7.3–12.9) ...

5.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.19.01834

Phase I Escalation and Expansion Study of ...

Bemarituzumab has demonstrated inhibition of FGFR2b phosphorylation and cell proliferation in FGFR2b-overexpressing gastric cancer xenograft ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05052801

Study Details | NCT05052801 | Bemarituzumab or Placebo ...

The main objective of this study is to compare efficacy of bemarituzumab combined with oxaliplatin, leucovorin, and 5-fluorouracil (5-FU) (mFOLFOX6) to ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8565817/

Preclinical characterization of bemarituzumab, an anti ...

Bemarituzumab is being developed as a cancer therapeutic, and we summarize here the key nonclinical data that supported moving it into clinical ...

8.

sciencedirect.com

sciencedirect.com/topics/medicine-and-dentistry/bemarituzumab

Bemarituzumab - an overview | ScienceDirect Topics

... safety profile and promising efficacy. The objective tumour response rate (ORR) was 43.2%, and the disease control rate (DCR) was 79.5% [52]. These results ...