Bemarituzumab + Chemotherapy for Stomach Cancer

(FORTITUDE-103 Trial)

Not currently recruiting at 66 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

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)

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment that combines bemarituzumab (an anti-FGFR2b antibody) with other cancer therapies to evaluate its safety and effectiveness for stomach cancer. The trial examines how well this combination works with various chemotherapy drugs and a medicine called nivolumab. People with advanced stomach cancer that surgery cannot cure might be suitable candidates. Participants must provide a tumor sample for the study and meet specific health criteria. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

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

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

Research has shown that bemarituzumab is generally safe when combined with chemotherapy. In earlier studies, patients who received bemarituzumab with chemotherapy drugs like CAPOX (capecitabine and oxaliplatin) did not encounter any new safety issues. Common side effects, such as tiredness and nausea, were manageable.

Another combination, SOX (S-1 and oxaliplatin) plus nivolumab, demonstrated a similar safety profile. Again, no new safety problems emerged, and side effects were mostly mild to moderate.

For bemarituzumab with CAPOX and nivolumab, studies also reported no new safety concerns. This combination was well-tolerated, with side effects similar to those in other combinations.

Overall, bemarituzumab in these combinations has been manageable for patients, with no major safety surprises. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because Bemarituzumab targets FGFR2b, a protein often linked with stomach cancer growth, offering a new mechanism of action compared to standard chemotherapy options like FOLFOX or ECF. Unlike typical treatments that target cancer cells broadly, Bemarituzumab is more precise, potentially leading to fewer side effects. Additionally, combining Bemarituzumab with chemotherapy regimens like CAPOX or SOX, and immunotherapy agent Nivolumab, might enhance the body's immune response to cancer, offering a more comprehensive attack on the tumor.

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

Research has shown that bemarituzumab, when combined with chemotherapy, may help treat stomach cancer. In this trial, participants may receive bemarituzumab with CAPOX (a mix of chemotherapy drugs). Studies have found that this combination significantly improved survival for patients with certain genetic traits, such as an excess of the protein FGFR2b. Another group in this trial will receive bemarituzumab with SOX (another chemotherapy mix) and nivolumab (an immune therapy), which also helped patients with stomach cancer live longer. Evidence suggests that bemarituzumab targets cancer cells with high levels of FGFR2b, a protein linked to cancer growth. Overall, these combinations have improved survival for patients with advanced stomach cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

This trial is for adults with advanced gastric or gastroesophageal junction cancer that can't be removed by surgery. Participants must have a performance score indicating they are relatively active, provide a tumor sample, and have no prior treatments for metastatic disease. They should not have certain heart diseases, brain metastases, severe neuropathy, recent major surgery or other cancers within the last 2 years.

Inclusion Criteria

My organs are working well.

I can provide a recent or new tumor sample for the study.

My cancer shows high FGFR2b levels as confirmed by a specific test.

Exclusion Criteria

I have received palliative radiotherapy within the last 14 days.

I haven't had treatment for advanced cancer but may have had treatment for early-stage cancer over 6 months ago.

I experience significant numbness or pain in my hands or feet.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive bemarituzumab in combination with S-1, oxaliplatin (SOX), and nivolumab to evaluate safety, tolerability, and efficacy

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bemarituzumab
• CAPOX
• Nivolumab
• SOX

Trial Overview The study tests bemarituzumab combined with chemotherapy (CAPOX or SOX) and possibly nivolumab in patients who haven't been treated before for their advanced stomach tumors. It aims to assess how safe this combination is and how well patients tolerate it.

How Is the Trial Designed?

Group I: Part 2: Bemarituzumab with SOX and Nivolumab. Experimental Treatment 3 Interventions

Group II: Part 1 Cohort D: Bemarituzumab with SOX and Nivolumab Experimental Treatment 3 Interventions

Group III: Part 1 Cohort C: Bemarituzumab with CAPOX and Nivolumab Experimental Treatment 3 Interventions

Group IV: Part 1 Cohort A: Bemarituzumab with CAPOX Experimental Treatment 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

Published Research Related to This Trial

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]

The FiGhTeR trial is investigating the safety and effectiveness of pemigatinib, an FGFR inhibitor, as a second-line treatment for patients with metastatic esophageal-gastric junction or gastric cancer who have become resistant to trastuzumab, the current first-line therapy.

This study aims to evaluate the 12-week progression-free survival rate in these patients while also collecting samples for research on the mechanisms of resistance to trastuzumab, highlighting the role of FGFR3 overexpression in treatment failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of the FGFR inhibitor pemigatinib in patients with metastatic esophageal-gastric junction/gastric cancer trastuzumab resistant: the FiGhTeR trial. Merz, V., Zecchetto, C., Simionato, F., et al.[2022]

Bemarituzumab, an FGFR2b inhibitor, has shown effectiveness in treating gastroesophageal adenocarcinoma with high levels of FGFR2b expression.

This finding suggests that targeting FGFR2b could be a promising therapeutic strategy for patients with this specific type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bemarituzumab Is Active in FGFR2b-High Gastroesophageal Adenocarcinoma. [2021]

In a phase 2 clinical trial involving 189 chemotherapy-naive patients with advanced gastric cancer, the addition of ramucirumab to S-1 and oxaliplatin did not improve progression-free survival or overall survival compared to S-1 and oxaliplatin alone.

The study found that the most common serious side effects of ramucirumab included decreased neutrophil count, hypertension, and anemia, but no new safety concerns were identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of First-line S-1 Plus Oxaliplatin With or Without Ramucirumab Followed by Paclitaxel Plus Ramucirumab on Advanced Gastric Cancer in East Asia: The Phase 2 RAINSTORM Randomized Clinical Trial. Yoshikawa, T., Muro, K., Shitara, K., et al.[2023]

In the phase II FIGHT trial, patients with advanced FGFR2b-positive gastric or gastroesophageal junction cancers who received bemarituzumab alongside chemotherapy experienced longer progression-free survival and overall survival.

Despite its efficacy in improving survival rates, bemarituzumab was linked to an increase in side effects, particularly eye problems, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FGFR Inhibitor Stymies Gastric Cancer. [2021]

Trastuzumab combined with chemotherapy (cisplatin and fluorouracil) significantly improves the prognosis for patients with HER2-positive gastric cancer, which is a serious subtype of gastric adenocarcinoma.

Adding pembrolizumab to trastuzumab and chemotherapy enhances the overall response rate, establishing it as the first-line treatment for HER2-positive gastric cancer, although challenges like innate resistance to trastuzumab remain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Advances in Treatment of Human Epidermal Growth Factor Receptor 2-Positve Gastric Cancer]. Wu, XQ., Ge, YP., Gong, XL., 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]

A systematic review of 10 trials involving 5526 patients showed that bevacizumab biosimilars have comparable efficacy and safety to reference biologics in treating advanced non-small cell lung cancer (NSCLC) and metastatic colorectal cancer (CRC).

The analysis indicated no significant differences in objective response rates, progression-free survival, or overall survival between bevacizumab biosimilars and standard treatments, suggesting that these biosimilars can be a viable alternative in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Bevacizumab Biosimilars Compared With Reference Biologics in Advanced Non-small Cell Lung Cancer or Metastatic Colorectal Cancer Patients: A Network Meta-Analysis. Xu, X., Zhang, S., Xu, T., et al.[2022]

Citations

1. amgen.com 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

Press Releases At an Interim Analysis, Bemarituzumab Plus Chemotherapy Significantly Improved Overall Survival in People With FGFR2b Overexpression ...

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

Bemarituzumab as first-line treatment for locally advanced or ... At this final analysis, bemarituzumab-mFOLFOX6 treatment continued to demonstrate promising clinical efficacy and manageable safety in FGFR2- ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03694522

NCT03694522 | A Study of Bemarituzumab (FPA144) ... The main objective of the Phase 2 part of the study is to evaluate the efficacy of bemarituzumab (FPA144), a targeted antibody, in combination with modified ...

4. oncologynewscentral.com oncologynewscentral.com/gastric-cancer/early-overall-survival-advantage-with-bemarituzumab-in-gastric-gej-cancers-attenuated-with-follow-up

Bemarituzumab's Survival Benefit in Gastric/GEJ Cancers ... The primary analysis of the FORTITUDE-101 trial showed an overall survival gain with bemarituzumab in the treatment of FGFR2b-overexpressing ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36244398/

Bemarituzumab in patients with FGFR2b-selected gastric ... Background: Outcomes are poor in patients with HER2-negative, advanced gastric or gastro-oesophageal junction adenocarcinomas. In this study, we ...

6. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/339258

A Study Evaluating Bemarituzumab in Combination With Other ... The main objectives of this study are to evaluate the safety and tolerability of bemarituzumab in combination with other anti-cancer therapies, ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34719330/

Preclinical characterization of bemarituzumab, an anti- ... Bemarituzumab (FPA144) is a first-in-class, humanized, afucosylated immunoglobulin G1 monoclonal antibody (mAb) directed against fibroblast growth factor ...