Bemarituzumab for Solid Cancers

(FORTITUDE-301 Trial)

Recruiting at137 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Amgen

Must not be taking: Anti-arrhythmics, Ophthalmic steroids

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

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing bemarituzumab, a new medication, to see if it is safe and can help fight tumors in patients, especially when other treatments have not worked well. Bemarituzumab has been previously studied for certain types of cancer.

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.

What data supports the effectiveness of the drug Bemarituzumab for solid cancers?

Research shows that Bemarituzumab, when used alone or with chemotherapy, can effectively slow down tumor growth in cancers that overexpress FGFR2b, a specific protein. It works by blocking signals that help cancer cells grow and by helping the immune system attack these cells. ^{1 2 3 4 5}

How is the drug Bemarituzumab unique in treating solid cancers?

Bemarituzumab is unique because it is a first-in-class monoclonal antibody that targets FGFR2b, a specific protein overexpressed in certain tumors, and works by blocking this protein's signaling and enhancing the immune system's ability to kill cancer cells. This dual mechanism makes it different from other treatments that may not specifically target FGFR2b or enhance immune response in the same way. ^{1 2 3 6 7}

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Bemarituzumab (Monoclonal Antibodies)

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

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]

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]

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]

References

1. United States 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. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Bemarituzumab with modified FOLFOX6 for advanced FGFR2-positive gastroesophageal cancer: FIGHT Phase III study design. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Preclinical characterization of bemarituzumab, an anti-FGFR2b antibody for the treatment of cancer. [2022]

4. Germany 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Phase I Study of Pembrolizumab (MK-3475; Anti-PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors. [2022]

6. England 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. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic analysis of phase 1 bemarituzumab data to support phase 2 gastroesophageal adenocarcinoma FIGHT trial. [2021]