BGB-B3227 + Tislelizumab for Advanced Cancer

Recruiting at 15 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: BeiGene

Disqualifiers: Cytokine release syndrome, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: Unknown

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new antibody treatment, BGB-B3227 (a MUC1 x CD16A bispecific antibody), both alone and with another drug, tislelizumab, for advanced cancers. The goal is to determine if these treatments are safe and effective against tumors with high levels of the protein mucin-1 (MUC1). Participants should have advanced solid tumors that can be measured and maintain good organ function. The study will explore different doses to identify the safest and most effective amount for patients. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Do I need to stop my current medications for the trial?

The trial information does not specify if 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 this trial's treatments are likely to be safe?

Research shows that BGB-B3227 is a promising new treatment. It targets specific proteins on cancer and immune cells, potentially helping the body fight cancer. However, this is the first time BGB-B3227 is being tested in humans, so limited information exists about its safety in people.

Earlier studies in the lab or on animals showed BGB-B3227's potential against certain cancers, but these studies do not always predict human responses.

Tislelizumab, an antibody already approved for some other cancers, is generally well-tolerated, though it can have side effects like any treatment.

Since this study is in its early phase, the main goal is to ensure the treatment's safety and determine the right dose. Researchers are collecting safety data in humans for the first time. Participants in this trial will help researchers learn about the safety of BGB-B3227 and its combination with tislelizumab in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BGB-B3227 and tislelizumab for advanced cancer because they offer a fresh approach compared to current treatments like chemotherapy and targeted therapies. BGB-B3227 is unique because it targets specific cancer cell pathways, potentially reducing side effects and enhancing effectiveness. Tislelizumab is an immunotherapy, which helps the immune system better recognize and attack cancer cells. Together, they could provide a powerful combination that might work even when other treatments don't, giving hope for improved outcomes in advanced cancer cases.

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

This trial studies BGB-B3227 both as a monotherapy and in combination with tislelizumab. In studies with mice, BGB-B3227 has shown dose-dependent tumor shrinkage. It targets proteins on cancer cells and natural killer (NK) cells, aiding the immune system in attacking the tumor. When combined with tislelizumab, which blocks a protein that hinders the immune system from fighting cancer, the effects appear enhanced. Although this combination has seen limited testing in humans, the science suggests it could be a strong approach against certain cancers. Early tests in animals and labs are promising, but further research is needed to confirm these results in people. ^{1 4 6 7 8}

Who Is on the Research Team?

Study Director

Principal Investigator

BeiGene

Are You a Good Fit for This Trial?

This trial is for people with advanced or metastatic solid tumors that show high levels of a protein called MUC1. Participants should be relatively active and able to care for themselves (ECOG ≤ 1), have organs functioning well, agree to use effective birth control, and have at least one tumor that can be measured using standard criteria.

Inclusion Criteria

At least 1 measurable lesion per RECIST v1.1

Willing to use a highly effective method of birth control

My organs are functioning well.

Exclusion Criteria

History of severe Infusion-Related Reactions (IRRs), allergic reactions, or hypersensitivity to any ingredients or components of the study treatments

I have an autoimmune disease that might come back.

I have had a severe reaction to a previous treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Sequential cohorts of increasing dose levels of BGB-B3227 are evaluated as monotherapy and in combination with tislelizumab

9 months

Dose Expansion

Sequential cohorts of increasing dose levels of BGB-B3227 are evaluated in combination with tislelizumab and chemotherapy

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• BGB-B3227
• Tislelizumab

Trial Overview The study is testing BGB-B3227, an antibody designed to fight cancer, both alone and paired with tislelizumab (another cancer-fighting drug) with or without chemotherapy. The goal is to find out how safe it is, what doses are best, how the body processes it, and its preliminary effects on shrinking tumors.

How Is the Trial Designed?

Group I: Phase 1b: Dose Expansion Experimental Treatment 3 Interventions

Sequential cohorts of increasing dose levels of BGB-B3227 will be evaluated in combination with tislelizumab and chemotherapy.

Group II: Phase 1a Part B: Dose Escalation (BGB-B3227 + tislelizumab) Experimental Treatment 2 Interventions

Sequential cohorts of increasing dose levels of BGB-B3227 will be evaluated in combination with tislelizumab.

Group III: Phase 1a Part A: Dose Escalation (BGB-B3227 Monotherapy) Experimental Treatment 1 Intervention

Sequential cohorts of increasing dose levels of BGB-B3227 will be evaluated as monotherapy.

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Published Research Related to This Trial

In a phase 3 trial involving 332 patients with advanced nonsquamous non-small cell lung cancer (nsq-NSCLC), the combination of tislelizumab and chemotherapy significantly improved progression-free survival (PFS) compared to chemotherapy alone, with a median PFS of 9.7 months versus 7.6 months.

The addition of tislelizumab also resulted in higher response rates and longer duration of response, making it a promising first-line treatment option for patients with advanced nsq-NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab Plus Chemotherapy as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC (RATIONALE 304): A Randomized Phase 3 Trial. Lu, S., Wang, J., Yu, Y., et al.[2021]

In a phase IA/IB study involving 451 patients with advanced solid tumors, tislelizumab demonstrated an acceptable safety profile, with most adverse events being mild (grade 1-2), and only 5.3% of patients discontinuing treatment due to side effects.

Tislelizumab showed promising antitumor activity, with 18% of patients in phase IA and 12% in phase IB achieving confirmed objective responses, leading to the recommendation of a dosing schedule of 200 mg every 3 weeks for future trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IA/IB study of single-agent tislelizumab, an investigational anti-PD-1 antibody, in solid tumors. Desai, J., Deva, S., Lee, JS., et al.[2021]

The phase I trial of MEDI5752, a bispecific antibody that targets both PD-1 and CTLA4, shows that the drug is well tolerated by patients.

Preliminary results indicate that MEDI5752 is active in treating various tumor types, with durable responses observed, suggesting potential effectiveness in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MEDI5752 Suppresses Two Immune Checkpoints. [2022]

Teclistamab, a bispecific antibody for treating relapsed or refractory multiple myeloma, showed a 63% overall response rate in a study of 165 heavily pretreated patients, but 72.1% experienced cytokine release syndrome (CRS), primarily mild to moderate in severity.

Management of CRS with tocilizumab significantly reduced the likelihood of subsequent CRS events (20% recurrence with tocilizumab vs. 62.2% without), indicating that proactive treatment can help manage side effects without compromising the efficacy of teclistamab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detailed overview of incidence and management of cytokine release syndrome observed with teclistamab in the MajesTEC-1 study of patients with relapsed/refractory multiple myeloma. Martin, TG., Mateos, MV., Nooka, A., et al.[2023]

Tislelizumab, an anti-PD-1 monoclonal antibody, shows improved progression-free survival and objective response rates in treating non-small cell lung cancer (NSCLC), especially when combined with chemotherapy, based on a review of four randomized controlled trials involving 1565 patients.

While tislelizumab is generally effective, it is associated with treatment-emergent adverse events, including significant hematologic issues and immune-mediated effects like hypothyroidism and pneumonitis, with a mortality rate from these events ranging from 3.2% to 4.2%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of tislelizumab, alone or in combination with chemotherapy, for the treatment of non-small cell lung cancer: a systematic review of clinical trials. Daei Sorkhabi, A., ZareDini, M., Fazlollahi, A., et al.[2023]

Tislelizumab, a monoclonal antibody targeting PD-1, was well tolerated in a study of 300 Chinese patients with advanced solid tumors, with no dose-limiting toxicities reported during the phase 1 portion.

The treatment showed antitumor activity, with 18% of patients achieving a confirmed clinical response, including a complete response in one case, indicating its potential effectiveness across multiple tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab in Chinese patients with advanced solid tumors: an open-label, non-comparative, phase 1/2 study. Shen, L., Guo, J., Zhang, Q., et al.[2021]

Tislelizumab is a modified PD-1 antibody that effectively inhibits tumor growth in various cancers, including Hodgkin's lymphoma and lung cancer, and has received multiple approvals in China for its use.

It has a favorable safety profile with common side effects like fatigue and anemia, and it offers economic advantages over other PD-1 inhibitors, making it a promising option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab: A Modified Anti-tumor Programmed Death Receptor 1 Antibody. Zhang, L., Geng, Z., Hao, B., et al.[2023]

In a phase II study with 70 patients suffering from relapsed/refractory classical Hodgkin lymphoma, tislelizumab showed a high overall response rate of 87.1% and a complete response rate of 67.1% after a median follow-up of 33.8 months, indicating its efficacy as a treatment option.

The treatment demonstrated a favorable safety profile, with 97.1% of patients experiencing treatment-related adverse events, but only 31.4% having severe (grade ≥3) events, and just 8.6% discontinuing treatment due to adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab for Relapsed/Refractory Classical Hodgkin Lymphoma: 3-Year Follow-up and Correlative Biomarker Analysis. Song, Y., Gao, Q., Zhang, H., et al.[2023]

In a study involving 180 patients with advanced solid tumors, the combination of pamiparib and tislelizumab demonstrated an overall objective response rate (ORR) of 20%, with the highest response (47.4%) observed in patients with triple-negative breast cancer (TNBC) who had BRCA1/2 mutations or homologous recombination deficiency.

While the treatment showed promising antitumor activity, it was associated with a significant incidence of treatment-emergent adverse events, with 61.7% of patients experiencing grade 3 or higher side effects, indicating that while the therapy is effective, careful monitoring for safety is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pamiparib in combination with tislelizumab in patients with advanced solid tumours: results from the dose-expansion stage of a multicentre, open-label, phase I trial. Friedlander, M., Mileshkin, L., Lombard, J., et al.[2023]

Citations

1. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_1/1789/758648/Abstract-1789-Preclinical-characterization-of-BGB

Preclinical characterization of BGB-B3227, a MUC1 x CD16A ... In mouse models, BGB-B3227 monotherapy demonstrated a dose-dependent anti-tumor efficacy, which was further enhanced when combining with an anti ...

2. beonemedinfo.com beonemedinfo.com/CongressDocuments/Zhu_Preclinical_BGB-B3227_AACR_Poster_2025.pdf

Preclinical characterization of BGB-B3227, a MUC1 x ... In mouse models, BGB-B3227 monotherapy demonstrated a dose-dependent anti-tumor efficacy. Furthermore, BGB-B3227 combined with an anti-PD-1 ...

3. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/anti-mucin-1-cd16a-bispecific-antibody-bgb-b3227

anti-mucin-1/CD16A bispecific antibody BGB-B3227 Upon administration, anti-MUC1/CD16A bispecific antibody BGB-B3227 targets and binds to CD16A expressed on natural killer (NK) cells and MUC1 expressed on the ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7712407/

Potential of Anti-MUC1 Antibodies as a Targeted Therapy ... In this review we present an overview of the antibodies targeting MUC1 in GI cancers, their potential role in immunotherapy (ie, antibody-drug and ...

5. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0191024

Single domain based bispecific antibody, Muc1-Bi-1, and its ... In vitro, the Muc1-Bi bispecific antibodies can recruit Natural Killer (NK) cells to drive potent and specific cell killing of Muc1-overexpressing tumor cells.

6. synapse.patsnap.com synapse.patsnap.com/drug/ae3c6f035806496ea50cdca4c9a25181

BGB-B3227 - Drug Targets, Indications, Patents A multicenter, open-label, Phase 1a/1b study to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity.

7. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/anti-mucin-1-cd16a-bispecific-antibody-bgb-b3227?pn=1

Clinical Trials Using Anti-mucin-1/CD16A Bispecific ... A Study of BGB-B3227 Alone and in Combination With Tislelizumab in Participants With Advanced or Metastatic Solid Tumors. Status: Active. Location: 5 ...

8. beonemedaffairs.com beonemedaffairs.com/us/congress-resources/

Congress Resources - BeOne Medical Affairs | US Preclinical characterization of BGB-B3227, a MUC1 x CD16A bispecific engager, for the treatment of MUC1-expressing solid tumors ... Updated safety & antileukemic ...