BG-C137 for Cancer

Recruiting at 22 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: BeiGene

Must not be taking: Topoisomerase inhibitors, FGFR2b-targeted ADCs

Disqualifiers: Corneal disorders, Brain metastasis, ILD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

68 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of BG-C137 in participants with advanced solid tumors.

Will I have to stop taking my current medications?

The trial requires that you stop taking any systemic antitumor therapy at least 14 days before starting the study drug. This includes targeted therapy, immunotherapy, chemotherapy, and investigational therapy. If you're on any of these, you will need to stop them before joining the trial.

What data supports the effectiveness of the drug BG-C137 for cancer?

Research shows that targeting the FGFR2 (fibroblast growth factor receptor 2) pathway, which BG-C137 is likely involved with, can be beneficial in treating cancers with FGFR2 mutations or gene amplifications. This pathway is important in tumor growth and progression, making it a promising target for cancer therapy. ^{1 2 3 4 5}

What makes the drug BG-C137 unique for cancer treatment?

BG-C137 is unique because it targets the FGFR2b receptor, which is involved in cancer cell growth and survival. This drug is designed to block the FGF/FGFR pathway, which is a key player in tumor growth and progression, offering a novel approach compared to traditional cancer therapies. ^{2 3 5 6 7}

Research Team

Study Director

Principal Investigator

BeiGene

Eligibility Criteria

This trial is for people with advanced solid tumors who have tried standard treatments without success or can't tolerate them. They need to have at least one measurable tumor, a life expectancy of 3+ months, and be in good enough health to perform daily activities (ECOG status 0-1). Adequate organ function is required, and they must agree to provide tissue samples.

Inclusion Criteria

My cancer is confirmed to be advanced or has spread to other parts.

My doctor expects me to live for at least 3 more months.

I have had 1-2 treatments for my advanced cancer, or no more standard treatments are suitable for me.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1a: Dose Escalation and Safety Expansion

Sequential cohorts of increasing dose levels of BG-C137 will be evaluated as monotherapy

Up to approximately 2 years

Phase 1b: Dose Expansion

Recommended Dose(s) of BG-C137 as determined from Phase 1a will be evaluated in select indications

Up to approximately 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• BG-C137

Trial Overview The study tests BG-C137, an experimental drug targeting FGFR2b proteins on cancer cells. It aims to assess the drug's safety, how well it's tolerated by patients, its behavior in the body (pharmacokinetics), its effect on tumors (pharmacodynamics), and initial effectiveness against tumors.

Participant Groups

Group I: Phase 1b: Dose Expansion Experimental Treatment 1 Intervention

Recommended Dose(s) of BG-C137 as determined from Ph1a will be evaluated in select indications

Group II: Phase 1a: Dose Escalation and Safety Expansion Experimental Treatment 1 Intervention

Sequential cohorts of increasing dose levels of BG-C137 will be evaluated as monotherapy

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Findings from Research

Dovitinib, an oral inhibitor targeting FGF, VEGF, and PDGF receptors, was found to be tolerable and showed antitumor activity in a trial involving 20 heavily pretreated patients with advanced renal cell carcinoma, with a maximum tolerated dose of 500 mg.

Out of the participants, 2 patients achieved a partial response and 12 had stable disease, indicating that dovitinib may be effective in managing tumor growth, especially in patients who have undergone multiple prior treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of dovitinib (TKI258), an oral FGFR, VEGFR, and PDGFR inhibitor, in advanced or metastatic renal cell carcinoma. Angevin, E., Lopez-Martin, JA., Lin, CC., et al.[2022]

In a study of 493 gastric cancer patients, FGFR2 expression was found to be heterogeneous, with 50.9% of tumors showing no FGFR2 expression, while 40% of those with high protein expression had FGFR2 gene amplification.

Although FGFR2 expression did not correlate with overall survival in the entire cohort, it was negatively associated with survival in diffuse-type gastric cancer, indicating that FGFR2-positive diffuse-type tumors may represent a subgroup with poorer outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FGFR2 overexpression and compromised survival in diffuse-type gastric cancer in a large central European cohort. Schrumpf, T., Behrens, HM., Haag, J., et al.[2022]

Fibroblast growth factors (FGFs) play a crucial role in tumor growth by facilitating communication between tumor cells and their surrounding environment, which can lead to tumor progression and resistance to therapies.

Targeting the FGF/FGFR pathway presents a promising strategy for cancer treatment, although developing effective drugs has been challenging due to the complexity and redundancy of the FGF family, highlighting the potential for dual-action therapies that combine antiangiogenic and antitumor effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blocking the FGF/FGFR system as a "two-compartment" antiangiogenic/antitumor approach in cancer therapy. Giacomini, A., Chiodelli, P., Matarazzo, S., et al.[2022]

The fibroblast growth factor (FGF) and its receptors (FGFRs) play a crucial role in the growth of certain human tumors, making them important targets for cancer therapy.

Strategies to inhibit FGF/FGFR signaling are being explored, including using FGFR expression to deliver targeted treatments to tumors and employing FGFs to reduce side effects of cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fibroblast growth factors in cancer: therapeutic possibilities. Jeffers, M., LaRochelle, WJ., Lichenstein, HS.[2019]

FGFR2 gene mutations and polymorphisms are linked to breast and gastric cancers, with aberrant FGFR2 signaling promoting tumor cell growth and survival, highlighting its role as a potential therapeutic target.

While FGFR2 inhibitors can be effective for treating cancers with FGFR2 mutations, using them for prevention in individuals with FGFR2 risk alleles may be harmful, as they could disrupt protective mechanisms against oxidative stress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FGFR2-related pathogenesis and FGFR2-targeted therapeutics (Review). Katoh, Y., Katoh, M.[2019]

Basic fibroblast growth factor (bFGF) significantly enhances the proliferation of human salivary adenoid cystic carcinoma (ACC) cell line ACC-2 in a dose-dependent manner, as shown by MTT assays and increased ERK activity.

The mechanism behind bFGF's effect involves upregulation of the ERK signaling pathway and Cyclin D1, along with inhibition of p21waf/cip1, indicating potential targets for new therapies in ACC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of basic fibroblast growth factor on the proliferation of human salivary adenoid cystic carcinoma cell line ACC-2 and extracellular signal-regulated kinase, Cyclin D1, p2waf/cip1 signaling pathway]. Ding, L., Zhu, SR., Xie, SX., et al.[2018]

Reducing FGFR2 expression in human colorectal cancer (CRC) cells significantly inhibited their migration, invasion, and tumor growth, indicating its crucial role in CRC progression.

The study suggests that FGFR2 could be a promising new therapeutic target for treating colorectal cancer, as it is more highly expressed at the invasive front of tumors compared to other areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overexpressed fibroblast growth factor receptor 2 in the invasive front of colorectal cancer: a potential therapeutic target in colorectal cancer. Matsuda, Y., Ishiwata, T., Yamahatsu, K., et al.[2022]

References

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

Phase I study of dovitinib (TKI258), an oral FGFR, VEGFR, and PDGFR inhibitor, in advanced or metastatic renal cell carcinoma. [2022]

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

FGFR2 overexpression and compromised survival in diffuse-type gastric cancer in a large central European cohort. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Blocking the FGF/FGFR system as a "two-compartment" antiangiogenic/antitumor approach in cancer therapy. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Fibroblast growth factors in cancer: therapeutic possibilities. [2019]

5. Greece pubmed.ncbi.nlm.nih.gov

FGFR2-related pathogenesis and FGFR2-targeted therapeutics (Review). [2019]

6. China pubmed.ncbi.nlm.nih.gov

[Effects of basic fibroblast growth factor on the proliferation of human salivary adenoid cystic carcinoma cell line ACC-2 and extracellular signal-regulated kinase, Cyclin D1, p2waf/cip1 signaling pathway]. [2018]

7. Ireland pubmed.ncbi.nlm.nih.gov

Overexpressed fibroblast growth factor receptor 2 in the invasive front of colorectal cancer: a potential therapeutic target in colorectal cancer. [2022]