BG-T187 for Cancer

Recruiting at 36 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: BeiGene

Must not be taking: Steroids, Immune suppressants

Disqualifiers: Brain metastasis, Active hepatitis C, others

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

Compensation: Varies

Number of Visits: Unknown

87 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called BG-T187, a potential drug for individuals with advanced solid tumors. As a Phase 1 study, it evaluates the safety and tolerability of the drug, both alone and in combination with other treatments. The trial is open to those diagnosed with advanced, metastatic, and hard-to-remove cancers who have already undergone treatment. Individuals with solid tumors that haven't responded well to other treatments might find this trial suitable. Participants have the opportunity to be among the first to receive this new treatment and assist researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify whether 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 BG-T187 is likely to be safe for humans?

Research has shown that BG-T187 is still undergoing tests to determine its safety and tolerability in people. This treatment is in the first phase of clinical trials, marking its initial use in humans. Earlier in the study, researchers tested different amounts of BG-T187 to identify safe and tolerable doses, assessing how much of the drug can be taken without serious side effects. As this is its first human trial, detailed safety information is still being collected. The process involves gradually increasing the dose to monitor for adverse reactions. This phase is crucial to ensure BG-T187 can be safely administered before advancing to later stages that evaluate its effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cancer?

Unlike the standard treatments for cancer, which often include chemotherapy, radiation, and surgery, BG-T187 is unique because it targets specific cancer pathways with precision, potentially minimizing damage to healthy cells. Researchers are excited about BG-T187 because it offers a new mechanism of action that could enhance treatment effectiveness and reduce side effects compared to traditional therapies. This targeted approach could lead to improved outcomes and a better quality of life for patients.

What evidence suggests that BG-T187 might be an effective treatment for cancer?

Research has shown that BG-T187, the investigational treatment in this trial, is a promising option for solid tumors. It targets specific pathways, EGFR and MET, which aid cancer growth. Early results suggest that BG-T187 can slow or halt tumor growth. Although still under study, BG-T187 is designed to block cancer signals, potentially working against various solid cancers. Previous studies using similar methods have shown positive results, particularly in non-small cell lung cancer. This positions BG-T187 as a hopeful option for future cancer treatments. ^{1 3 5 6 7}

Who Is on the Research Team?

Study Director

Principal Investigator

BeiGene

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that have been treated before. They must be able to consent, be at least 18 years old or the legal age in their area, and have a good performance status (ECOG ≤ 1). Participants need to have at least one measurable or nonmeasurable lesion according to specific criteria and adequate organ function.

Inclusion Criteria

Able to provide a signed and dated written informed consent prior to any study-specific procedures, sampling, or data collection

I have an advanced cancer that cannot be removed by surgery and I've been treated before.

I have at least one tumor that can be measured.

Exclusion Criteria

I do not have an untreated brain tumor, spinal cord compression, or leptomeningeal disease.

I have not taken any antibiotics, antifungals, or antivirals in the last 14 days.

Prior severe allergic reactions or hypersensitivity to the active ingredient and excipients of BG-T187 or other monoclonal antibodies

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1a: Monotherapy Dose Escalation

Sequential cohorts of increasing dose levels of BG-T187 will be evaluated as monotherapy

Approximately 2 years

Phase 1a: Monotherapy Safety Expansion

BG-T187 dose levels that have been determined to be safe and tolerable in Part A will be investigated

Approximately 2 years

Phase 1b: Monotherapy Dose Expansion

The monotherapy dose expansion phase will begin once the BG-T187 monotherapy recommended dose for expansion (RDFE) and dosing schedule have been determined from Parts A and B in Phase 1a

Approximately 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BG-T187

Trial Overview The study is testing BG-T187 alone and combined with other therapies on people with advanced solid tumors. It's an early-stage trial looking at safety, how well it works, dosage levels, body effects of the drug (pharmacokinetics), and its action mechanism (pharmacodynamics).

How Is the Trial Designed?

Group I: Phase 1b: Monotherapy Dose Expansion with Subcutaneous Administration Experimental Treatment 1 Intervention

Participants will receive BG-T187 monotherapy at the recommended dose(s) for expansion (RDFE) determined in Phase 1a.

Group II: Phase 1b: Combination Therapy: BG-T187 + Other Therapeutic Agents Experimental Treatment 2 Interventions

Participants will receive BG-T187 in combination with Other Therapeutic Agents.

Group III: Phase 1a: Part B: Monotherapy Dose Escalation with Subcutaneous Administration Experimental Treatment 1 Intervention

Sequential cohorts of increasing dose levels of BG-T187 will be evaluated as monotherapy.

Group IV: Phase 1a: Part A: Monotherapy Dose Escalation with Intravenous Administration Experimental Treatment 1 Intervention

Sequential cohorts of increasing dose levels of BG-T187 will be evaluated as monotherapy.

Group V: Phase 1a Part C: Safety Expansion Experimental Treatment 1 Intervention

BG-T187 dose levels that have been determined to be safe and tolerable in Part A will be investigated.

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Published Research Related to This Trial

Tiragolumab, a TIGIT inhibitor, shows promise in treating solid cancers, particularly non-small cell lung cancer, based on results from phase I and II trials.

The combination of tiragolumab with the PD-L1 inhibitor atezolizumab has demonstrated statistically significant efficacy in multiple solid tumors, suggesting a potential new treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiragolumab Impresses in Multiple Trials. [2021]

Agonizing GITR with the anti-GITR antibody DTA-1.mIgG2a, combined with depleting regulatory T cells (Tregs), can enhance the ratio of effector T cells (Teffs) to Tregs in tumors, potentially leading to tumor shrinkage.

A new quantitative systems pharmacology model was developed to analyze the effects of DTA-1.mIgG2a in mouse tumor models, providing insights into optimizing treatment strategies by balancing Treg depletion and Teff activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative systems pharmacology model of GITR-mediated T cell dynamics in tumor microenvironment. Ji, Y., Madrasi, K., Knee, DA., et al.[2023]

Blinatumomab shows a favorable safety profile in pediatric patients with B-cell acute lymphoblastic leukemia (ALL), associated with a lower risk of serious adverse events, febrile neutropenia, and infections compared to traditional chemotherapy.

While blinatumomab does not significantly increase the risk of cytokine release syndrome or seizures, it is linked to a higher risk of encephalopathy, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of blinatumomab in pediatric patients with acute lymphoblastic leukemia: A systematic review and meta-analysis. Marrapodi, MM., Mascolo, A., di Mauro, G., et al.[2022]

Blinatumomab, a bispecific T-cell engager, has shown a 43% response rate in adult patients with relapsed or refractory Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia, with 40% of responders achieving complete remission and proceeding to stem cell transplantation.

Management strategies, such as premedication with dexamethasone and gradual dose escalation, have successfully reduced the incidence and severity of adverse effects like cytokine release syndrome and neurotoxicity associated with early use of blinatumomab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab: Bridging the Gap in Adult Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia. Folan, SA., Rexwinkle, A., Autry, J., et al.[2018]

BSG (CD147) is significantly upregulated in several cancer types, indicating that high levels of BSG may increase susceptibility to SARS-CoV-2 and correlate with poor survival outcomes in certain cancers, such as LGG and LIHC.

The study identified small molecules (cordycepin, HEA, m62A, and UMP) that can downregulate BSG expression in cancer cells, suggesting potential therapeutic strategies to reduce COVID-19 severity and cancer progression by targeting BSG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of BSG/CD147 gene expression on diagnostic, prognostic and therapeutic strategies towards malignant cancers and possible susceptibility to SARS-CoV-2. Fu, J., Song, B., Du, J., et al.[2023]

In a study of 159 bladder cancer patients, high levels of CD147 were found to be associated with increased tumor proliferation and poorer prognosis, indicating its potential role as a biomarker for aggressive cancer behavior.

CD147 promotes bladder cancer cell proliferation by increasing the expression of gasdermin D (GSDMD), suggesting that targeting CD147 could be a therapeutic strategy to inhibit tumor growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD147 Expression Is Associated with Tumor Proliferation in Bladder Cancer via GSDMD. Peng, J., Jiang, H., Guo, J., et al.[2022]

A new fusion cell line, FLB2C, was created by fusing mouse lung cancer cells with active B lymphocytes, which successfully expressed both lung cancer antigens and the B7 molecule.

The oncogenicity of the FLB2C cells was significantly reduced, as they showed slower growth, no colony formation in soft agar, and did not form tumors when injected into mice, suggesting potential for developing improved lung cancer vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Establishment and growth characteristics of mouse lung cancer B₇ fusion cells]. Lin, P., Lu, Y., Zhang, J., et al.[2010]

TG01, an immunotherapy targeting KRAS mutations, was found to be well tolerated in patients with resected pancreatic adenocarcinoma, with a high immune response rate of 95% in the main cohort and 92% in the modified cohort.

The study reported favorable median overall survival (33.1 months for the main cohort and 34.3 months for the modified cohort) and disease-free survival (13.9 months and 19.5 months, respectively), suggesting TG01/GM-CSF combined with gemcitabine may enhance treatment outcomes compared to standard gemcitabine alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TG01/GM-CSF and adjuvant gemcitabine in patients with resected RAS-mutant adenocarcinoma of the pancreas (CT TG01-01): a single-arm, phase 1/2 trial. Palmer, DH., Valle, JW., Ma, YT., et al.[2023]

AMG 228, a monoclonal antibody targeting GITR, was well tolerated in a phase 1 study with 30 patients, reaching a maximum dose of 1200 mg without any dose-limiting toxicities, indicating a favorable safety profile.

Despite achieving target coverage and favorable pharmacokinetics, AMG 228 did not demonstrate T-cell activation or anti-tumor activity in patients with advanced solid tumors, suggesting that further investigation is needed to assess its therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose escalation results from a first-in-human, phase 1 study of glucocorticoid-induced TNF receptor-related protein agonist AMG 228 in patients with advanced solid tumors. Tran, B., Carvajal, RD., Marabelle, A., et al.[2019]

The monoclonal antibody ICT01 has shown promise in preclinical studies by activating unique antitumor γ9δ2 T cells and promoting their movement to tumors.

A phase I/IIa clinical trial is currently underway, and early results indicate that ICT01 is producing similar effects in human patients as observed in preclinical models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy Activates Antitumor γ9δ2 T Cells. [2021]

Blinatumomab, a bi-specific T-cell engager antibody targeting CD19, has shown effectiveness in treating patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL), particularly those with minimal residual disease, leading to its recent FDA approval.

The treatment is administered via continuous intravenous infusion due to its short serum half-life and has a favorable safety profile, although it can cause central nervous system events and cytokine release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential for bispecific T-cell engagers: role of blinatumomab in acute lymphoblastic leukemia. Le Jeune, C., Thomas, X.[2019]

Blinatumomab is a promising new treatment for adults with relapsed or refractory B-cell acute lymphoblastic leukemia, showing effectiveness in targeting and destroying tumor cells by engaging both T-cells and B-cells.

While there are potential side effects like immunological toxicities and cytokine release syndrome, most patients tolerate blinatumomab well, indicating a favorable safety profile compared to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical use of blinatumomab for B-cell acute lymphoblastic leukemia in adults. Lee, KJ., Chow, V., Weissman, A., et al.[2022]

The Mdm2 inhibitor nutlin-3 showed significant effectiveness in inducing apoptosis in nonseminomatous testicular germ cell tumor (TGCT) cell lines with wild-type p53, suggesting a potential therapeutic strategy for patients with these tumors.

When combined with cisplatin, nutlin-3 enhanced the anti-cancer effects in wild-type p53 cell lines, indicating that targeting the Mdm2-p53 pathway could improve treatment outcomes for high-risk TGCT patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic potential of Mdm2 inhibition in malignant germ cell tumours. Bauer, S., Mühlenberg, T., Leahy, M., et al.[2016]

CD147 is a key protein overexpressed in various aggressive cancers, playing a crucial role in cancer growth, survival, and metastasis through multiple signaling pathways.

Targeting CD147 with therapies, such as monoclonal antibodies, has shown promise in enhancing treatment efficacy and reducing side effects in chemoradiotherapy and other cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD147: an integral and potential molecule to abrogate hallmarks of cancer. Nyalali, AMK., Leonard, AU., Xu, Y., et al.[2023]

This study analyzed immune checkpoint receptor expression on T cells from 172 treatment-naïve cancer patients, revealing increased levels of PD-1 and Tim-3 on tumor-infiltrating T cells compared to circulating T cells, which may indicate a dysfunctional antitumor response.

The identification of specific 'shared' subsets of T cells with multiple checkpoint receptors could inform the development of more effective mono-blockade or combinatorial therapies to enhance T-cell immunity while minimizing adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comprehensive Analysis of Key Immune Checkpoint Receptors on Tumor-Infiltrating T Cells From Multiple Types of Cancer. Li, X., Wang, R., Fan, P., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06598800

Study of BG-T187 Alone and in Combination With Other ... This is a first-in-human (FIH), Phase 1a/1b, open-label, multicenter, dose escalation and dose expansion study to evaluate the safety, tolerability, ...

2. withpower.com withpower.com/trial/phase-1-neoplasms-9-2024-d5d50

BG-T187 for Cancer Tiragolumab, a TIGIT inhibitor, shows promise in treating solid cancers, particularly non-small cell lung cancer, based on results from phase I and II trials.

3. beonemedicines.com beonemedicines.com/science/pipeline/

BeOne Pipeline Explore BeOne Medicines, formerly BeiGene, with a cutting-edge cancer pipeline using top science and innovation to target deadly cancers.

4. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2024-0553.html

A phase 1 study investigating the safety, tolerability ... A phase 1 study investigating the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of BG-T187, an EGFR×MET trispecific antibody, alone ...

5. tipranks.com tipranks.com/news/company-announcements/beone-medicines-advances-in-oncology-with-promising-bg-t187-study

BeOne Medicines Advances in Oncology with Promising ... The intervention being tested is BG-T187, an experimental drug administered intravenously. It is designed to target EGFR and MET pathways, ...

6. synapse.patsnap.com synapse.patsnap.com/drug/4444e615f6294c5eba4cf7b4388d30c1

BG-T187 - Drug Targets, Indications, Patents A Phase 1 Study Investigating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of BG-T187, an EGFR×MET Trispecific Antibody, ...

7. ctv.veeva.com ctv.veeva.com/study/study-of-bg-t187-alone-and-in-combination-with-other-therapeutic-agents-in-participants-with-advance

Study of BG-T187 Alone and in Combination With Other ... BG-T187 dose levels that have been determined to be safe and tolerable in Part A will be investigated. Treatment: Drug: Drug: BG-T187. Phase 1b: ...