Bemarituzumab + Chemotherapy + Nivolumab for Stomach Cancer

(FORTITUDE-102 Trial)

Not currently recruiting at 494 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: HER2 positive, CNS metastases, cardiac disease, others

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: 14-day or 21-day cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with stomach cancer that cannot be surgically removed or has metastasized. The aim is to determine if adding bemarituzumab, an experimental drug, to standard chemotherapy and nivolumab, which aids the immune system in fighting cancer, improves patient survival compared to standard treatment alone. Ideal candidates for this trial have stomach cancer that is inoperable and have received minimal prior treatment. As a Phase 3 trial, this study represents the final step before FDA approval, providing patients an opportunity to access 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, when combined with chemotherapy, has produced positive effects in treating stomach cancer. Specifically, the FIGHT trial demonstrated improved survival rates. However, another study noted a decrease in these benefits, indicating that while the drug shows promise, it is not without limitations.

For the combination of bemarituzumab and nivolumab, early results suggest they may enhance tumor responsiveness. The primary focus remains on the safety of using these treatments together.

Earlier trials have assessed how well participants tolerated these drugs, and the trials have now progressed to a more advanced stage, suggesting some confidence in their safety. However, it is crucial to remember that any new treatment can carry risks.

Participants in the trial experienced varying treatment durations, highlighting that individual responses can differ. Those considering participation should carefully weigh both the potential benefits and risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for stomach cancer, like chemotherapy regimens including mFOLFOX6 or CAPOX, work by killing rapidly dividing cancer cells. But bemarituzumab offers something different. It targets FGFR2b, a protein that is overexpressed in some stomach cancers, making it more precise in attacking cancer cells. Researchers are excited about this approach because it could potentially lead to better outcomes with fewer side effects than traditional chemotherapy. Additionally, combining bemarituzumab with nivolumab, an immunotherapy, might boost the immune system's ability to fight cancer, offering a promising new avenue for treatment.

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

In this trial, participants will receive different treatment combinations to evaluate their effectiveness for stomach cancer. One group will receive bemarituzumab with chemotherapy and nivolumab. Previous studies have shown that combining bemarituzumab with chemotherapy helped people with stomach cancer live longer without their cancer worsening. On average, people lived 8.6 months without their cancer worsening when taking bemarituzumab, compared to 6.7 months with a placebo. Another analysis showed that this combination significantly improved overall survival in patients with high levels of a protein called FGFR2b, which is found in some stomach cancers. These findings suggest that bemarituzumab, especially when used with chemotherapy and nivolumab, may help extend the time people live without their cancer progressing. This treatment combination could be effective for those with certain types of stomach cancer. ^{1 3 4 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 adenocarcinoma that can't be removed by surgery. Participants must have an ECOG performance status of 0-1, indicating they are fully active or restricted in physically strenuous activity but ambulatory and able to carry out work of a light nature. They should not have had prior treatments for their metastatic disease, except possibly one dose of mFOLFOX6 with or without nivolumab.

Inclusion Criteria

Aspartate aminotransaminase (AST) and Alanine aminotransaminase (ALT) <3 x upper limit of normal (ULN) (or < 5 x ULN if liver involvement)

My blood clotting time is normal or near normal, or I've been on a stable blood thinner dose for 6 weeks.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

My cancer is HER2 positive.

I have a serious heart condition.

I have moderate to severe 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

Safety Lead-in

Participants receive bemarituzumab with mFOLFOX6 and nivolumab to determine the recommended phase 3 dose based on safety and tolerability

Varies

Treatment

Participants receive bemarituzumab or placebo with chemotherapy (mFOLFOX6 or CAPOX) and nivolumab

14-day or 21-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 5-fluorouracil
• Bemarituzumab
• Leucovorin
• Nivolumab
• Oxaliplatin

Trial Overview The study tests the safety and effectiveness of bemarituzumab combined with chemotherapy (mFOLFOX6 or CAPOX) and nivolumab versus placebo plus the same chemotherapies and nivolumab. The goal is to see if adding bemarituzumab improves survival compared to the standard treatment without it.

How Is the Trial Designed?

Group I: Part 2: Bemarituzumab with chemotherapy (mFOLFOX6 or CAPOX) and Nivolumab Experimental Treatment 3 Interventions

Participants will be administered bemarituzumab at the RP3D determined from Part 1 in combination with mFOLFOX6 and nivolumab on a 14-day cycle. Or participants will be administered bemarituzumab in combination with CAPOX and nivolumab on a 21-day cycle.

Group II: Part 1 Safety Lead-in: Bemarituzumab with mFOLFOX6 and Nivolumab Experimental Treatment 3 Interventions

Participants will be administered bemarituzumab at different doses with mFOLFOX6 and nivolumab to determine the recommended phase 3 dose (RP3D) based on occurrence of dose-limiting toxicities (DLTs), and on an evaluation of the overall safety, tolerability, and pharmacokinetics (PK).

Group III: Part 2: Placebo with chemotherapy (mFOLFOX6 or CAPOX) and Nivolumab Placebo Group 3 Interventions

Participants will be administered placebo comparator in combination with mFOLFOX6 and nivolumab on a 14-day cycle. Or participants will be administered placebo comparator in combination with CAPOX and nivolumab on a 21-day cycle.

5-fluorouracil is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Esophageal cancer
• Anal cancer

Approved in European Union as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Esophageal cancer
• Anal cancer

Approved in Canada as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Esophageal cancer
• Anal cancer

Approved in Japan as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Esophageal cancer
• Anal cancer

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

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]

S-1, an oral chemotherapy drug combining tegafur with modulators, has shown advantages over standard 5-FU-based treatments for gastric cancer in large Phase III studies, making it a recommended option in treatment guidelines.

S-1, either alone or in combination with cisplatin, is non-inferior to traditional 5-FU regimens while offering greater convenience and reduced toxicity, highlighting its potential for higher efficacy in treating gastrointestinal cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

S-1 for the treatment of gastrointestinal cancer. Satoh, T., Sakata, Y.[2022]

In a study of 570 patients with stage III colorectal cancer, three different administration types of 5-fluorouracil (5-FU) in FOLFOX treatment showed similar disease-free survival (DFS) and overall survival (OS) rates, indicating comparable efficacy.

While all treatment regimens were manageable in terms of toxicity, the modified FOLFOX-6 group experienced more grade 1-2 adverse events like thrombocytopenia and neuropathy, suggesting that while efficacy is similar, side effects may vary among the different regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The comparison of FOLFOX regimens with different doses of 5-FU for the adjuvant treatment of colorectal cancer: a multicenter study. Akdeniz, N., Kaplan, MA., Uncu, D., et al.[2021]

Irinotecan has been approved for patients with colorectal cancer who do not respond to 5-fluorouracil and has shown effectiveness both alone and in combination with other agents like 5-fluorouracil and leucovorin.

Oxaliplatin, when combined with 5-fluorouracil and leucovorin, results in a higher response rate compared to 5-fluorouracil alone, and it has shown clinical activity even in patients whose disease progressed on previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel chemotherapeutic agents for gastrointestinal cancers. Royce, ME., Pazdur, R.[2019]

5-fluorouracil (5-FU) remains a key treatment for various solid tumors, particularly colorectal cancer, but has low single-agent response rates of only 10%-30%, highlighting the need for improved efficacy.

The review discusses newer prodrugs of 5-FU, such as capecitabine, UFT, and S-1, which aim to enhance antitumor activity while potentially reducing the toxic side effects associated with traditional 5-FU treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical studies of three oral prodrugs of 5-fluorouracil (capecitabine, UFT, S-1): a review. Malet-Martino, M., Martino, R.[2022]

The modified FOLFIRI regimen, which combines low doses of leucovorin and 5-fluorouracil with irinotecan, showed an overall response rate of 38.6% in 44 patients with advanced gastric cancer, indicating its efficacy as a first-line treatment.

The treatment was found to be safe, with manageable toxicities; major side effects included grade 1 to 2 anemia and neutropenia, but there were no treatment-related deaths reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of irinotecan with biweekly, low dose leucovorin and bolus and continuous infusion 5-fluorouracil (modified FOLFIRI) as first line therapy for patients with recurrent or metastatic gastric cancer. Kim, BG., Oh, SY., Kwon, HC., et al.[2018]

Chemotherapy significantly increases survival and improves quality of life in patients with advanced gastric carcinoma compared to supportive measures alone.

Current standard treatments include infusional 5-FU combined with cisplatin or ECF, while newer third-generation combinations with taxanes and irinotecan show similar effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Patient with stomach cancer with metastases. What is the value of chemotherapy?]. Wilke, H., Stahl, M., Vanhoefer, U.[2013]

In a phase II study involving 58 patients with advanced gastric cancer, the combination of docetaxel, fluorouracil, and leucovorin (TFL) showed a moderate overall response rate of 26%, with 4 complete and 11 partial responses observed.

The TFL regimen was found to have manageable toxicity, with neutropenia being the most common severe side effect (30% of patients), and no toxic deaths reported, indicating a favorable safety profile for this chemotherapy combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination docetaxel (Taxotere), fluorouracil, and leucovorin (TFL), as first-line chemotherapy in advanced gastric cancer: a Hellenic Cooperative Oncology Group phase II study. Papakostas, P., Tsavdaridis, D., Kosmidis, P., 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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38308771/

final analysis of the randomized phase 2 FIGHT trial The median PFS (95% confidence interval [CI]) was 9.5 months (7.3-13.7) with bemarituzumab-mFOLFOX6 and 7.4 months (5.7-8.4) with placebo- ...

3. dailyreporter.esmo.org dailyreporter.esmo.org/esmo-congress-2025/gastrointestinal-cancers/first-line-bemarituzumab-improves-short-term-survival-in-gastric-or-gastroesophageal-junction-cancer-overexpressing-fgfr2b

1L bemarituzumab in gastric or gastroesophageal junction ... Median progression-free survival was 8.6 months with bemarituzumab versus 6.7 months with placebo (HR 0.71; 95% CI 0.53–0.95; p=0.019) at a ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2949819825000585

a single-arm phase II study evaluating bemarituzumab ... The trial aims to evaluate the efficacy and safety of bemarituzumab in combination with paclitaxel and ramucirumab as the second-line treatment for patients ...

5. aacrjournals.org aacrjournals.org/cdnews/news/2645/Stomach-Cancer-Drug-Wanes-in-Phase-III-Trial

Stomach Cancer Drug Wanes in Phase III Trial - AACR Journals The mAb bemarituzumab (Amgen, Zai Labs) saw a drop in survival benefit in the phase III FORTITUDE-101 study, as compared with an earlier ...

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

Health-related quality of life with bemarituzumab plus ... At the final analysis after a minimum follow-up of 24 months (data cut-off 13 May 2022), bemarituzumab plus mFOLFOX6 showed improved progression-free survival ...

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 ...