BG-T187 for Cancer

Recruiting at 19 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

Trial Summary

What is the purpose of this trial?

This is a first-in-human (FIH), Phase 1a/1b, open-label, multicenter, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of BG-T187 alone and in combination with other therapeutic agents in participants with advanced solid tumors.

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.

What data supports the effectiveness of the drug BG-T187 for cancer?

The research on AMG 228, a similar type of drug targeting the GITR protein, shows that it can be safe and potentially effective in treating advanced solid tumors. Additionally, studies on GITR-related treatments suggest that they can help shrink tumors by affecting immune cells in the tumor environment. ^{1 2 3 4 5}

What is known about the safety of BG-T187 in humans?

The treatment, known as blinatumomab, has been used in patients with certain types of leukemia and has shown some serious side effects like cytokine release syndrome (a severe immune reaction) and neurological issues (such as seizures). However, with careful management, many patients tolerate the treatment relatively well. ^{6 7 8 9 10}

What makes the drug BG-T187 unique for cancer treatment?

BG-T187 is unique because it targets CD147, a protein overexpressed in many aggressive cancers, which plays a key role in cancer growth and spread. By focusing on CD147, BG-T187 may help prevent cancer cells from growing and spreading, potentially offering a new approach compared to existing treatments. ^{11 12 13 14 15}

Research Team

Study Director

Principal Investigator

BeiGene

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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

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.

Group II: Phase 1a: Part B: Monotherapy 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.

Group III: Phase 1a: Part A: Monotherapy Dose Escalation Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Findings from Research

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]

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]

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]

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]

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, 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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2023]

2. England 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. [2019]

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

Tiragolumab Impresses in Multiple Trials. [2021]

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

Therapeutic potential of Mdm2 inhibition in malignant germ cell tumours. [2016]

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

Quantitative systems pharmacology model of GITR-mediated T cell dynamics in tumor microenvironment. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

The safety of blinatumomab in pediatric patients with acute lymphoblastic leukemia: A systematic review and meta-analysis. [2022]

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

Immunotherapy Activates Antitumor γ9δ2 T Cells. [2021]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Potential for bispecific T-cell engagers: role of blinatumomab in acute lymphoblastic leukemia. [2019]

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

Blinatumomab: Bridging the Gap in Adult Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia. [2018]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical use of blinatumomab for B-cell acute lymphoblastic leukemia in adults. [2022]

11. Netherlands 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. [2023]

12. Switzerland pubmed.ncbi.nlm.nih.gov

CD147: an integral and potential molecule to abrogate hallmarks of cancer. [2023]

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

CD147 Expression Is Associated with Tumor Proliferation in Bladder Cancer via GSDMD. [2022]

14. Switzerland pubmed.ncbi.nlm.nih.gov

A Comprehensive Analysis of Key Immune Checkpoint Receptors on Tumor-Infiltrating T Cells From Multiple Types of Cancer. [2021]

15. China pubmed.ncbi.nlm.nih.gov

[Establishment and growth characteristics of mouse lung cancer B₇ fusion cells]. [2010]