Bemarituzumab + Chemotherapy for Stomach Cancer

(FORTITUDE-101 Trial)

Recruiting at 369 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Amgen

Must not be taking: FGF-FGFR inhibitors

Disqualifiers: CNS disease, Cardiac disease, Others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 3.5 years

547 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing whether adding bemarituzumab to standard chemotherapy helps patients live longer. It targets patients whose tumors have a specific marker (FGFR2b). The treatment works by blocking a protein that helps cancer cells grow.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on anticoagulant therapy, you must be on a stable dose for 6 weeks before joining the trial.

What data supports the effectiveness of the drug Bemarituzumab combined with chemotherapy for stomach cancer?

Research shows that Bemarituzumab, when used with chemotherapy, has shown clinical activity in patients with advanced gastric cancer that overexpresses FGFR2b, improving outcomes like overall survival and progression-free survival. ^{1 2 3 4 5}

Is Bemarituzumab + Chemotherapy safe for humans?

Studies have shown that Bemarituzumab, when combined with chemotherapy regimens like mFOLFOX6, has been evaluated for safety in patients with gastric and gastroesophageal cancers. In these studies, no dose-limiting toxicities were reported, indicating it is generally safe for human use in these conditions. ^{1 2 4 6 7}

What makes the drug Bemarituzumab + Chemotherapy unique for stomach cancer?

Bemarituzumab is a novel drug that targets FGFR2b, a specific protein found in some stomach cancers, and is combined with a chemotherapy regimen called mFOLFOX6. This combination is unique because it specifically targets tumors that overexpress FGFR2b, potentially improving outcomes for patients with this type of cancer. ^{1 4 8 9 10}

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

Adults with advanced gastric or gastroesophageal junction cancer that can't be removed by surgery, showing high levels of FGFR2b protein. They must have a good performance status (ECOG ≤1), measurable disease per RECIST criteria, and adequate organ function. Not eligible if they have brain metastases, significant heart problems, certain eye disorders, HER2 positive cancer, recent major surgery or other treatments for their cancer.

Inclusion Criteria

I am fully active and can carry on all pre-disease activities without restriction.

I can safely receive mFOLFOX6 chemotherapy.

My tumor shows high FGFR2b levels based on a recent test.

Exclusion Criteria

My cancer is HER2 positive.

I have had recent eye problems, including corneal defects or a corneal transplant.

I have been treated with drugs targeting the FGF-FGFR pathway.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive bemarituzumab or placebo combined with mFOLFOX6 chemotherapy

Up to approximately 3.5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 3.5 years

Treatment Details

Interventions

• Bemarituzumab
• mFOLFOX6
• Placebo

Trial Overview The trial is testing the effectiveness of bemarituzumab combined with mFOLFOX6 chemotherapy versus a placebo plus mFOLFOX6 in improving survival rates. Bemarituzumab targets the FGFR2b protein overexpressed in some cancers.

Participant Groups

Group I: Bemarituzumab with mFOLFOX6 Experimental Treatment 2 Interventions

Group II: Placebo with mFOLFOX6 Active Control 2 Interventions

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

Zai Lab (China only)

Collaborator

Trials

1

Recruited

550+

Findings from Research

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]

The modified FOLFOX6 (mFOLFOX6) regimen was found to be an effective and tolerable neoadjuvant chemotherapy for gastric cancer, with a 45.8% radiological response rate and a 49.2% rate of significant histological regression in patients undergoing surgery.

The ypTNM stage and the degree of histological regression (GHR) were identified as important prognostic factors for overall survival, suggesting that GHR could help guide postoperative chemotherapy decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of a modified FOLFOX6 regimen as neoadjuvant chemotherapy for locally advanced gastric cancer. Wang, X., Zhao, L., Liu, H., et al.[2022]

In a study of 66 patients with chemotherapy-refractory metastatic colorectal cancer, the combination of cetuximab with bevacizumab and mFOLFOX6 showed manageable safety, but significant toxicity led to a high discontinuation rate, with 56% of patients stopping treatment before disease progression.

Despite not causing excessive life-threatening toxicity, the addition of cetuximab resulted in a notable number of patients experiencing severe side effects, prompting the conclusion that this combination therapy should not be used together for treating metastatic colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab is associated with excessive toxicity when combined with bevacizumab Plus mFOLFOX6 in metastatic colorectal carcinoma. Ocean, AJ., Polite, B., Christos, P., et al.[2021]

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]

In a study of 285 patients with wild-type KRAS exon 2 metastatic colorectal cancer, the combination of panitumumab with mFOLFOX6 showed a significant improvement in overall survival (OS) compared to bevacizumab with mFOLFOX6, with median OS of 34.2 months versus 24.3 months, respectively.

While progression-free survival (PFS) was similar between the two treatment arms, patients with wild-type RAS tumors (including KRAS and NRAS) experienced greater clinical benefits from panitumumab, suggesting its efficacy in this specific genetic context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. Schwartzberg, LS., Rivera, F., Karthaus, M., et al.[2022]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

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

A phase II study of a modified FOLFOX6 regimen as neoadjuvant chemotherapy for locally advanced gastric cancer. [2022]

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

Cetuximab is associated with excessive toxicity when combined with bevacizumab Plus mFOLFOX6 in metastatic colorectal carcinoma. [2021]

4. 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]

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

PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Phase Ib study of drozitumab combined with first-line mFOLFOX6 plus bevacizumab in patients with metastatic colorectal cancer. [2020]

7. 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]

8. Bosnia and Herzegovina pubmed.ncbi.nlm.nih.gov

First-line treatment of patients with HER2-positive metastatic gastric and gastroesophageal junction cancer. [2022]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Outcomes of modified FOLFOX-6 as first line treatment in patients with advanced gastric cancer in a single institution; retrospective analysis. [2022]

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

Oxaliplatin in combination with 5-fluorouracil (5-FU) and leucovorin (LV) in patients with metastatic gastric cancer (MGC). [2022]