BGB-B3227 + Tislelizumab for Advanced Cancer

Recruiting at 11 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

Trial Summary

What is the purpose of this trial?

This is a first-in-human (FIH), open-label, multicenter dose escalation and expansion study of BGB-B3227, a humanized immunoglobulin G1 (IgG1) antibody. The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of BGB-B3227 as a monotherapy or in combination with tislelizumab with or without chemotherapy in participants with selected advanced or metastatic solid tumors. The study will also identify recommended dose(s) for expansion (RDFE\[s\]) of BGB-B3227 administered alone and in combination with tislelizumab.

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.

What data supports the effectiveness of the drug BGB-B3227 + Tislelizumab for advanced cancer?

Tislelizumab has shown promising anti-tumor effects in various cancers, including lung, liver, and gastric cancers, and has been approved for several cancer types in China. It has also demonstrated improved outcomes when combined with chemotherapy for advanced lung cancer. ^{1 2 3 4 5}

What is known about the safety of Tislelizumab in humans?

Tislelizumab has an acceptable safety profile, with common side effects including tiredness, low red blood cell count (anemia), and reduced white blood cell count (neutrophils). Serious side effects have included breathing problems and liver damage. ^{1 4 6 7 8}

What makes the drug BGB-B3227 + Tislelizumab unique for advanced cancer?

The drug BGB-B3227 + Tislelizumab is unique because Tislelizumab is a specially engineered antibody that targets the PD-1 protein on immune cells, helping the immune system better recognize and attack cancer cells. It is designed to minimize unwanted interactions with other immune components, potentially reducing resistance to treatment and improving effectiveness in various cancers. ^{1 4 5 7 9}

Research Team

Study Director

Principal Investigator

BeiGene

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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 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]

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]

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]

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]

References

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

Tislelizumab for Relapsed/Refractory Classical Hodgkin Lymphoma: 3-Year Follow-up and Correlative Biomarker Analysis. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Tislelizumab in Chinese patients with advanced solid tumors: an open-label, non-comparative, phase 1/2 study. [2021]

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

MEDI5752 Suppresses Two Immune Checkpoints. [2022]

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

Tislelizumab: A Modified Anti-tumor Programmed Death Receptor 1 Antibody. [2023]

5. United States 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. [2021]

6. England 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. [2023]

7. England 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. [2023]

8. United States 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. [2023]

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

Phase IA/IB study of single-agent tislelizumab, an investigational anti-PD-1 antibody, in solid tumors. [2021]