BGB-B2033 + Tislelizumab for Advanced Cancer

Recruiting at 17 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

Trial Summary

What is the purpose of this trial?

This study is a first-in-human (FIH) Phase 1 study of BGB-B2033 to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of the BGB-B2033 in participants with advanced or metastatic hepatocellular carcinoma (HCC), alpha-fetoprotein (AFP)-producing gastric cancer (GC), extragonadal yolk sac tumors, non-dysgerminomas, or glypican-3 (GPC3)-positive squamous non-small cell lung cancer (NSCLC). The study will also identify the recommended Phase 2 dose (RP2D) of BGB-B2033 alone and in combination with tislelizumab for subsequent studies. BGB-B2033 will be administered by intravenous infusion. The Phase 1 study will be conducted in 2 parts: Part A (Monotherapy Dose Escalation and Safety Expansion) and Part B (Combination Dose Escalation and Safety Expansion).

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.

What data supports the effectiveness of the drug BGB-B2033 + Tislelizumab for advanced cancer?

Tislelizumab has shown promising anti-tumor effects in various cancers, including lung, liver, and gastric cancers, and is approved in China for several cancer types. It has been studied in combination with other drugs, showing potential to improve outcomes in advanced solid tumors. ^{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 fatigue, anemia (low red blood cell count), and decreased neutrophil count (a type of white blood cell). More serious risks include respiratory infections or failure and liver injury. ^{1 3 5 6 7}

What makes the drug BGB-B2033 + Tislelizumab unique for advanced cancer?

The combination of BGB-B2033 and Tislelizumab is unique because Tislelizumab is a specially designed antibody that targets the PD-1 protein to help the immune system fight cancer, and it has been engineered to reduce resistance by minimizing unwanted interactions with other immune cells. This combination aims to enhance the immune response against cancer cells, offering a novel approach compared to standard treatments. ^{1 2 3 6 8}

Research Team

Study Director

Principal Investigator

BeiGene

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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]

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]

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]

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]

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, 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]

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]

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]

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

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

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

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

4. England 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. [2023]

5. 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]

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

Model-based population pharmacokinetic analysis of tislelizumab in patients with advanced tumors. [2023]

7. England 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. [2021]

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

Tislelizumab: First Approval. [2020]