Bemarituzumab + Chemotherapy for Stomach Cancer

(FORTITUDE-101 Trial)

Not currently recruiting at 460 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for stomach cancer that cannot be surgically removed or has spread extensively. Researchers aim to determine if adding bemarituzumab, a potential new drug, to a standard chemotherapy mix helps patients live longer compared to the standard treatment alone. The trial targets individuals whose cancer cells display a specific marker called FGFR2b, identified through a lab test. Suitable candidates have advanced or metastatic stomach cancer and no severe heart problems or untreated brain issues. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients access to potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that bemarituzumab, combined with the chemotherapy treatment mFOLFOX6, has been tested in people with stomach cancer. These studies found that this combination can help patients with certain types of tumors live longer, and no unexpected safety problems emerged.

Most patients handled the treatment well, although some experienced common chemotherapy side effects like nausea or tiredness, typical for many cancer treatments. The studies did not identify any unusual or severe side effects specifically caused by bemarituzumab, indicating that the treatment is generally well tolerated when used with mFOLFOX6.

As research continues, scientists will gain further insights into the safety of this treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for stomach cancer?

Researchers are excited about Bemarituzumab for stomach cancer because it targets the FGFR2b protein, which is associated with tumor growth in some cancers. Unlike traditional chemotherapy, which attacks rapidly dividing cells broadly, Bemarituzumab specifically aims at cancer cells expressing this protein. This targeted approach could potentially lead to more effective treatment with fewer side effects, offering new hope for patients with FGFR2b-positive gastric cancers.

What evidence suggests that this trial's treatments could be effective for stomach cancer?

This trial will compare the effectiveness of bemarituzumab combined with chemotherapy (mFOLFOX6) to a placebo combined with mFOLFOX6 for treating stomach cancer. Research has shown that combining bemarituzumab with mFOLFOX6 may help treat stomach cancer. In one study, patients who received bemarituzumab with mFOLFOX6 lived for an average of 17.9 months, compared to 12.5 months for those who received a placebo with mFOLFOX6. Another study found that patients taking bemarituzumab went an average of 12.9 months without their tumor growing, while those on a placebo went 8.2 months. Additionally, the treatment lasted longer, with bemarituzumab working for 11.9 months compared to 7.5 months for the placebo. These results suggest that bemarituzumab could be a helpful treatment option for some patients with stomach cancer. ^{3 4 6 7 8}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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

Bemarituzumab as first-line treatment for locally advanced or ... The median DOR was 11.9 months (95% CI 6.9, 17.3) with bemarituzumab-mFOLFOX6 (n = 37) and 7.5 months (95% CI 4.3, 13.8) with placebo-mFOLFOX6 ( ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2949819824000566

Health-related quality of life with bemarituzumab plus ... In the phase II, randomized, double-blind FIGHT trial (NCT03694522), treatment with bemarituzumab plus mFOLFOX6 resulted in improvements in progression-free ...

3. onclive.com onclive.com/view/bemarituzumab-chemo-combo-translates-to-os-advantage-in-fgfr2b-gastric-gej-cancer

Bemarituzumab/Chemo Combo Translates to OS ... Bemarituzumab plus mFOLFOX6 improved overall survival in FGFR2b-overexpressing gastric/GEJ cancer, with initial median OS of 17.9 months vs 12.5 ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38861192/

Bemarituzumab plus mFOLFOX6 as first-line treatment in ... Median PFS (95% confidence interval [CI]) was 12.9 months (8.8-17.9) with bemarituzumab-mFOLFOX6 and 8.2 months (5.6-10.3) with placebo-mFOLFOX6 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03694522

NCT03694522 | A Study of Bemarituzumab (FPA144) ... A phase 1/2, multicenter, global, double-blind, randomized, controlled study designed to evaluate the safety, tolerability, efficacy, and pharmacokinetics (PK)

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38308771/

final analysis of the randomized phase 2 FIGHT trial Conclusions: In FGFR2b-positive advanced GC, the combination of bemarituzumab-mFOLFOX6 led to numerically longer median PFS and OS compared with ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS4164

Phase 3 study of bemarituzumab + mFOLFOX6 versus ... In the phase 2 FIGHT study (Wainberg, 2021; Catenacci, 2021), bemarituzumab + mFOLFOX6 improved progression-free survival (PFS; HR, 0.68; 95% CI ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03694522

NCT03694522 | A Study of Bemarituzumab (FPA144) ... The Phase 1 safety run-in is an open-label dose-escalation of bemarituzumab + mFOLFOX6 in patients with GI tumors (not FGFR2 selected) that is reported ...