Bemarituzumab + Chemotherapy + Nivolumab for Stomach Cancer

(FORTITUDE-102 Trial)

Recruiting at 410 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

515 Participants Needed

Trial Summary

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 combination Bemarituzumab + Chemotherapy + Nivolumab for stomach cancer?

Research shows that 5-fluorouracil (5-FU), a key component of this drug combination, is widely used and effective in treating gastric cancer. Additionally, combining 5-FU with other drugs like leucovorin and oxaliplatin has been shown to improve response rates in gastrointestinal cancers. ^{1 2 3 4 5}

What safety information is available for the combination of Bemarituzumab, Chemotherapy, and Nivolumab in humans?

5-fluorouracil (5-FU), a component of the treatment, has been used in various cancers and is known to cause side effects like myelotoxicity (bone marrow damage), hand-foot syndrome (skin reaction on palms and soles), and other toxicities depending on the dosage schedule. In a study of 5-FU with other drugs for gastric cancer, significant toxicity was noted, including some deaths related to treatment. This highlights the importance of monitoring and managing side effects during treatment. ^{3 6 7 8 9}

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

This treatment is unique because it combines Bemarituzumab, a novel antibody targeting FGFR2b, with chemotherapy and Nivolumab, an immune checkpoint inhibitor, offering a new approach for patients with specific genetic markers in advanced gastric cancer. ^{1 10 11 12 13}

What is the purpose of this trial?

The main objective of Part 1 is to evaluate the safety and tolerability of bemarituzumab plus 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) and nivolumab. The main objective Part 2 is to compare efficacy of bemarituzumab plus chemotherapy (mFOLFOX6 or capecitabine combined with oxaliplatin (CAPOX)) and nivolumab to placebo plus chemotherapy (mFOLFOX6 or CAPOX) and nivolumab as assessed by overall survival.

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

References

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

S-1 for the treatment of gastrointestinal cancer. [2022]

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

Novel chemotherapeutic agents for gastrointestinal cancers. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

Allicin Reduces 5-fluorouracil-resistance in Gastric Cancer Cells through Modulating MDR1, DKK1, and WNT5A Expression. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Infusional 5-fluorouracil and mitomycin C: an effective regimen in the treatment of advanced gastric cancer. [2013]

5. United States 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. [2018]

6. Germany 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. [2021]

7. Japan 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. [2022]

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

An EORTC Gastrointestinal Group evaluation of the combination of sequential methotrexate and 5-fluorouracil, combined with adriamycin in advanced measurable gastric cancer. [2017]

9. England pubmed.ncbi.nlm.nih.gov

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

10. Germany pubmed.ncbi.nlm.nih.gov

[Patient with stomach cancer with metastases. What is the value of chemotherapy?]. [2013]

11. Italy pubmed.ncbi.nlm.nih.gov

A pilot study of adjuvant chemotherapy with double modulation of 5-fluorouracil by methotrexate and leucovorin in gastric cancer patients. [2013]

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

Status of treatment for advanced gastric carcinoma. [2019]

13. 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]