Bemarituzumab + Chemotherapy for Stomach Cancer

(FORTITUDE-103 Trial)

Recruiting at 37 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

80 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called bemarituzumab combined with other cancer treatments (S-1, oxaliplatin, and nivolumab). It aims to see if this combination is safe and effective for treating cancer patients. The treatment works by directly attacking cancer cells and helping the immune system fight the cancer.

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.

What data supports the effectiveness of the drug Bemarituzumab + Chemotherapy for Stomach Cancer?

Research shows that Bemarituzumab, when combined with chemotherapy, has demonstrated 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 safe for human use?

Bemarituzumab has been tested in clinical trials for stomach cancer and has shown some side effects, including eye problems. However, it has been generally safe in humans when used with chemotherapy, although more side effects were noted compared to chemotherapy alone. ^{1 2 6 7 8}

What makes the drug Bemarituzumab unique for treating stomach cancer?

Bemarituzumab is unique because it targets FGFR2b, a specific protein overexpressed in some stomach cancers, and works by blocking this protein's signaling and enhancing the immune system's ability to attack cancer cells. This drug is combined with chemotherapy and has shown to improve survival in patients with FGFR2b-positive gastric cancer, although it may cause more side effects like eye problems. ^{1 2 6 8 9}

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

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]

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 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]

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]

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]

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 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]

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]

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]

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

Bemarituzumab in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma (FIGHT): a randomised, double-blind, placebo-controlled, phase 2 study. [2023]

3. England 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. [2022]

4. United States 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. [2023]

5. China pubmed.ncbi.nlm.nih.gov

[Advances in Treatment of Human Epidermal Growth Factor Receptor 2-Positve Gastric Cancer]. [2022]

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

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

7. Switzerland 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. [2022]

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

FGFR Inhibitor Stymies Gastric Cancer. [2021]

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

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