BGB-26808 + Tislelizumab for Cancer

Recruiting at 22 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: BeiGene

Must not be taking: Corticosteroids, Immunosuppressants, others

Disqualifiers: Uncontrolled diabetes, Active autoimmune diseases, others

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

Compensation: Varies

Number of Visits: Unknown

107 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open-label, multicenter, and nonrandomized dose escalation and dose expansion study to evaluate BGB-26808 as monotherapy or in combination with tislelizumab in participants with advanced solid tumors. The main purpose of this study is to explore the recommended dosing for BGB-26808.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot have taken certain treatments like corticosteroids or other immunosuppressive medications within 14 days before starting the study. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug BGB-26808 + Tislelizumab for 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. Tyrosine kinase inhibitors, like BGB-26808, have been effective in treating different tumors by blocking signals that help cancer cells grow. ^{1 2 3 4 5}

Is the combination of BGB-26808 and Tislelizumab safe for humans?

Tislelizumab, a part of this treatment, has been studied for safety in patients with various solid tumors, and it is generally considered safe, though specific side effects can occur. However, there is no specific safety data available for the combination of BGB-26808 and Tislelizumab. ^{4 5 6 7 8}

What makes the drug BGB-26808 + Tislelizumab unique for cancer treatment?

BGB-26808 combined with Tislelizumab is unique because it combines a novel HPK1 inhibitor (BGB-26808) with an anti-PD-1 antibody (Tislelizumab), potentially enhancing the immune system's ability to fight cancer by targeting different pathways. This combination may offer a new approach for patients who have not responded to other treatments. ^{4 5 6 9 10}

Research Team

Study Director

Principal Investigator

BeiGene

Eligibility Criteria

This trial is for adults with advanced solid tumors that can't be removed by surgery and have had prior treatment. They must have at least one measurable tumor, agree to use effective birth control, provide a tissue sample, and be in good physical condition (ECOG ≤ 1).

Inclusion Criteria

You must be willing to sign a document that details your understanding of the study prior to any related activities.

I can provide a sample of my tumor tissue.

I agree to use effective birth control during and after the study for the required time.

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-26808 will be evaluated as monotherapy and in combination with tislelizumab

Approximately 1 month

Dose Expansion

Recommended doses for expansion (RDFEs) for BGB-26808 in combination with tislelizumab plus chemotherapy will be evaluated

Approximately 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 12 months

Treatment Details

Interventions

• BGB-26808
• Tislelizumab

Trial Overview The study is testing BGB-26808 alone or combined with Tislelizumab in patients with solid tumors. It's an open-label trial aiming to find the best dose of BGB-26808.

Participant Groups

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

Recommended doses for expansion (RDFEs) for BGB-26808 from Phase 1a in combination with tislelizumab plus chemotherapy will be evaluated.

Group II: Phase 1a: Dose Escalation Experimental Treatment 2 Interventions

Sequential cohorts of increasing dose levels of BGB-26808 will be evaluated as monotherapy and in combination with tislelizumab.

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Findings from Research

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]

Tyrosine kinases (TKs) are key targets in cancer therapy due to their role in tumor growth and development, and blocking their activity has led to effective treatments for various cancers, including leukemia and solid tumors.

Imatinib, a well-known TK inhibitor, has revolutionized the treatment of chronic myelogenous leukemia, demonstrating the significant impact of TK blockers in clinical oncology, with several other promising inhibitors currently in development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tyrosine kinase blockers: new hope for successful cancer therapy. Pytel, D., Sliwinski, T., Poplawski, T., et al.[2019]

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]

Rezivertinib demonstrated a high objective response rate of 64.6% in patients with locally advanced or metastatic NSCLC harboring the EGFR T790M mutation, indicating its efficacy after previous EGFR TKI therapies.

The safety profile of rezivertinib was favorable, with 83.2% of patients experiencing treatment-related adverse events, but only 19.9% having severe (grade 3 or higher) events, and notably, no cases of interstitial lung disease were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Rezivertinib (BPI-7711) in Patients With Locally Advanced or Metastatic/Recurrent EGFR T790M-Mutated NSCLC: A Phase 2b Study. Shi, Y., Wu, S., Wang, K., et al.[2023]

ASP8273, a new tyrosine kinase inhibitor for non-small-cell lung cancer, did not demonstrate improved progression-free survival compared to standard treatments erlotinib or gefitinib, with median PFS of 9.3 months for ASP8273 versus 9.6 months for the comparator group.

Patients receiving ASP8273 experienced a higher rate of severe treatment-emergent adverse events (54.7%) compared to those on erlotinib/gefitinib (43.5%), leading to the study's discontinuation due to concerns over toxicity and limited efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase III, randomized, open-label study of ASP8273 versus erlotinib or gefitinib in patients with advanced stage IIIB/IV non-small-cell lung cancer. Kelly, RJ., Shepherd, FA., Krivoshik, A., et al.[2023]

In a clinical trial involving 20 patients with EGFR T790M-mutated non-small cell lung cancer (NSCLC), SH-1028 demonstrated manageable safety and promising antitumor activity, particularly at a dose of 200 mg once daily.

The overall objective response rate (ORR) was 40%, with a notable 75% ORR in the 200 mg cohort, indicating that SH-1028 could be an effective treatment option for patients who have progressed after previous EGFR TKI therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, efficacy, and pharmacokinetics of SH-1028 in EGFR T790M-positive advanced non-small cell lung cancer patients: A dose-escalation phase 1 study. He, J., Ma, P., Zhao, D., et al.[2023]

Tislelizumab, a PD-1 inhibitor, significantly improved the overall response rate (ORR) and disease control rate (DCR) in patients with malignant solid tumors, with odds ratios of 2.59 and 1.78, respectively, based on a meta-analysis of seven phase III trials involving 3478 participants.

The treatment also demonstrated improved overall survival (OS) and progression-free survival (PFS), with hazard ratios of 0.71 and 0.68, indicating that tislelizumab is an effective option for patients with solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tislelizumab for malignant solid tumor: a systematic review and meta-analysis of phase III randomized trials. Abushanab, AK., Mustafa, MT., Mousa, MT., 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, 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]

BPI-15086, a novel third-generation EGFR-TKI, was found to be safe and well-tolerated in a phase I study involving 17 patients with EGFR T790M-mutated non-small-cell lung cancer, with no serious adverse events leading to drug discontinuation.

The treatment showed an objective response rate of 17.7% and a disease control rate of 47.1%, indicating potential efficacy in this patient population, warranting further clinical investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and efficacy of BPI-15086 in patients with EGFR T790M-mutated advanced non-small-cell lung cancer: results from a phase I, single-arm, multicenter study. Xing, P., Zheng, X., Wang, Y., et al.[2022]

References

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

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

2. Netherlands pubmed.ncbi.nlm.nih.gov

Tyrosine kinase blockers: new hope for successful cancer therapy. [2019]

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

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

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

Efficacy and Safety of Rezivertinib (BPI-7711) in Patients With Locally Advanced or Metastatic/Recurrent EGFR T790M-Mutated NSCLC: A Phase 2b Study. [2023]

5. England pubmed.ncbi.nlm.nih.gov

A phase III, randomized, open-label study of ASP8273 versus erlotinib or gefitinib in patients with advanced stage IIIB/IV non-small-cell lung cancer. [2023]

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

Safety, efficacy, and pharmacokinetics of SH-1028 in EGFR T790M-positive advanced non-small cell lung cancer patients: A dose-escalation phase 1 study. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tislelizumab for malignant solid tumor: a systematic review and meta-analysis of phase III randomized trials. [2023]

8. 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]

9. 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]

10. England pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and efficacy of BPI-15086 in patients with EGFR T790M-mutated advanced non-small-cell lung cancer: results from a phase I, single-arm, multicenter study. [2022]