BGB-B2033 + Tislelizumab for Advanced Cancer

Recruiting at 21 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: BeiGene

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Autoimmune diseases, Brain metastasis, others

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

Compensation: Varies

Number of Visits: Unknown

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called BGB-B2033, used alone or with another drug, tislelizumab, to assess its safety and effectiveness for people with certain advanced cancers. The cancers under study include liver cancer, some stomach cancers, specific germ cell tumors, and a type of lung cancer. Individuals with these advanced-stage cancers, which cannot be surgically removed, might be suitable candidates. The study aims to determine the optimal dose and evaluate the treatment's impact on the cancer. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken certain treatments like corticosteroids or immunosuppressive medications within 14 days before starting the study drugs.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that BGB-B2033 is a new drug designed to target specific cancer cells. This trial marks its first test in humans, so no previous information exists about its effects on people. At this stage, safety information remains limited, and researchers aim to understand how people react to the drug and what side effects might occur.

When combined with tislelizumab, it is important to note that tislelizumab has been studied before. Research has shown that it is generally safe when used alone or with chemotherapy. This offers some reassurance about its safety, but the effects of using it with BGB-B2033 are still under investigation.

Overall, this trial is in its early stages, focusing primarily on safety and determining the right dose levels. Participants might experience side effects, but this is part of the process to understand how the treatment works. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BGB-B2033 and Tislelizumab for advanced cancer because these treatments take a novel approach compared to traditional options. BGB-B2033 is unique because it targets a specific pathway that may enhance the immune system's ability to fight cancer cells more effectively than traditional chemotherapy. Tislelizumab, on the other hand, is an immunotherapy that blocks a protein called PD-1, which can help the immune system recognize and attack cancer cells, potentially leading to better outcomes. Together, they offer a combination strategy that could provide a more powerful and targeted attack against cancer, which is why researchers are eager to explore their potential benefits.

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

Research has shown that BGB-B2033 has promising results in early studies. In tests with mice that had tumors containing the protein glypican-3 (GPC3), BGB-B2033 demonstrated strong effects against the tumors. This drug links tumor cells to immune cells, activating them to fight the cancer. In this trial, some participants will receive BGB-B2033 as a monotherapy in Part A, which involves dose escalation and safety expansion.

Tislelizumab is another drug that helps the immune system recognize and attack cancer cells, and it has been effective in treating some cancers, such as non-small cell lung cancer. In Part B of this trial, researchers will combine BGB-B2033 with Tislelizumab to potentially boost the immune response against tumors. Although human studies provide limited information, these early findings suggest that this combination could effectively treat advanced cancers. ^{1 2 3 4 6}

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 certain advanced or metastatic cancers, including liver cancer (HCC), AFP-producing stomach cancer, yolk sac tumors outside the gonads, and GPC3-positive squamous lung cancer. Participants need at least one evaluable lesion and must be in good physical condition with an ECOG score ≤ 1.

Inclusion Criteria

I can sign and understand the consent form for this study.

I have been diagnosed with liver cancer.

My cancer is a type of germ cell tumor not originating in the ovaries.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Part A (Monotherapy Dose Escalation and Safety Expansion)

Participants receive ascending dose levels of BGB-B2033 monotherapy to assess safety, tolerability, and preliminary antitumor activity

Up to approximately 2 years

Treatment - Part B (Combination Dose Escalation and Safety Expansion)

Participants receive BGB-B2033 in combination with tislelizumab to assess safety, tolerability, and preliminary antitumor activity

Up to 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

• BGB-B2033
• Tislelizumab

Trial Overview The study tests BGB-B2033 alone or combined with Tislelizumab to evaluate safety, dosage levels, body's drug handling (PK), biological effects (PD), and initial effectiveness against specific solid tumors. It includes a dose escalation phase followed by a safety expansion phase.

How Is the Trial Designed?

Group I: Part B (Combination Dose Escalation and Safety Expansion) Experimental Treatment 2 Interventions

Cohorts of BGB-B2033 in combination with tislelizumab

Group II: Part A (Monotherapy Dose Escalation and Safety Expansion) Experimental Treatment 1 Intervention

Ascending dose levels of BGB-B2033 monotherapy

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Published Research Related to This Trial

Tislelizumab is an anti-PD-1 monoclonal antibody developed as an immunotherapy for cancer, specifically approved in December 2019 in China for relapsed or refractory classical Hodgkin's lymphoma after at least two prior chemotherapy treatments.

The drug has shown promise in treating both hematological cancers and advanced solid tumors, indicating its potential for future approvals in additional cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab: First Approval. Lee, A., Keam, SJ.[2020]

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]

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 PD-1 inhibitor designed to reduce resistance to therapy, showed a linear pharmacokinetic profile in a study involving 2,596 cancer patients, indicating consistent drug behavior across various doses (0.5-10 mg/kg or a flat 200 mg dose).

Key factors like body weight and tumor characteristics influenced drug clearance, but these had no clinically significant effects, supporting the use of a standard 200 mg dose every 3 weeks for diverse patient populations without the need for adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Model-based population pharmacokinetic analysis of tislelizumab in patients with advanced tumors. Budha, N., Wu, CY., Tang, Z., 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]

The combination of sitravatinib and tislelizumab was generally well-tolerated in patients with locally advanced/metastatic non-small cell lung cancer (NSCLC), with treatment-related adverse events occurring in 98.4% of patients, but no new safety concerns were identified.

Objective response rates varied by cohort, with the highest response (57.1%) in patients with PD-L1-positive non-squamous histology who had not received prior systemic therapy, indicating potential efficacy in treatment-naïve populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SAFFRON-103: a phase 1b study of the safety and efficacy of sitravatinib combined with tislelizumab in patients with locally advanced or metastatic non-small cell lung cancer. Zhao, J., Yu, X., Huang, D., et al.[2023]

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]

Atezolizumab treatment in 615 patients with previously treated advanced non-small cell lung cancer showed a median overall survival of 11.1 months and a median progression-free survival of 2.7 months, indicating its efficacy in this population.

The safety profile was manageable, with treatment-related serious adverse events occurring in 7.8% of patients and immune-related adverse events in 8.3%, confirming that atezolizumab can be safely administered even to patients with severe renal impairment and other challenging conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary results from TAIL: a global single-arm safety study of atezolizumab monotherapy in a diverse population of patients with previously treated advanced non-small cell lung cancer. Ardizzoni, A., Azevedo, S., Rubio-Viqueira, B., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06427941

NCT06427941 | A Phase 1 Study of BGB-B2033, Alone or ... This study is a first-in-human (FIH) Phase 1 study of BGB-B2033 to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-07658

A Phase 1 Study of BGB-B2033, Alone or in Combination ... This study is a first-in-human (FIH) Phase 1 study of BGB-B2033 to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary ...

3. beonemedinfo.com beonemedinfo.com/CongressDocuments/Li_Preclinical_BGB-B2033_AACR_Poster_2025.pdf

BGB-B2033, a novel 4-1BB/GPC3 bispecific antibody, ... In humanized 4-1BB knock-in mice bearing human GPC3-expressing tumors, BGB-B2033 exhibited potent, dose-associated single-agent efficacy as well ...

4. app.trialscreen.org app.trialscreen.org/trials/phase-1-bgb-b2033-alone-or-combination-tislelizumab-participants-advanced-trial-nct06427941

A Phase 1 Study of BGB-B2033, Alone or in Combination ... A Phase 1 study of BGB-B2033 in solid tumors. A study to evaluate the safety and effectiveness of an experimental drug called BGB-B2033, alone or in ...

5. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK616788

Tislelizumab for treating advanced non-small-cell lung cancer ... Tislelizumab for treating advanced non-small-cell lung cancer after platinum-based chemotherapy (terminated appraisal). National Institute for ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40578840/

Long-term safety analysis of pooled data for tislelizumab as ... Tislelizumab's safety profile, as monotherapy or combined with chemotherapy, remains consistent with previous reports across tumor types.