BGB-15025 + Tislelizumab for Advanced Cancers

Recruiting at 46 trial locations

Overseen By BeiGene

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: 21

157 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug, BGB-15025, alone and with an immune-boosting drug, tislelizumab, in patients with advanced cancer. The goal is to see if these treatments are safe and to find the best dose.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you must stop them at least 14 days before the first dose of the study treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you may need to stop them at least 14 days before starting the trial treatment.

What data supports the idea that BGB-15025 + Tislelizumab for Advanced Cancers is an effective treatment?

The available research shows that Tislelizumab, when used in combination with other treatments, has shown promising results in treating various advanced cancers. For example, in patients with advanced urothelial carcinoma, Tislelizumab demonstrated a 24% response rate, meaning nearly a quarter of patients saw their cancer shrink or disappear. Additionally, Tislelizumab has been compared to another drug, Pembrolizumab, for lung cancer treatment, and both showed similar effectiveness in improving patient outcomes. This suggests that Tislelizumab, including when combined with BGB-15025, could be an effective option for treating advanced cancers. ^{1 2 3 4 5}

What data supports the effectiveness of the drug BGB-15025 + Tislelizumab for advanced cancers?

Tislelizumab has shown promising anti-tumor effects in various cancers, including lung, liver, and esophageal cancers, and has been approved for several cancer types in China. It has demonstrated meaningful benefits in patients with advanced urothelial carcinoma, with a 24% response rate and manageable side effects. ^{1 2 3 4 5}

What safety data is available for BGB-15025 and Tislelizumab in treating advanced cancers?

Tislelizumab, an anti-PD-1 antibody, has been studied in various cancers and shows an acceptable safety profile. Common adverse effects include fatigue, anemia, and decreased neutrophil count, with serious events like respiratory infection or hepatic injury being rare. In combination with chemotherapy for non-small cell lung cancer, it was well tolerated with a safety profile similar to the overall population. In urothelial carcinoma, common treatment-related adverse events were anemia and pyrexia, with some grade 3-4 events like anemia and hyponatremia. Three deaths were possibly related to treatment. Overall, Tislelizumab demonstrates manageable safety in these studies. ^{2 4 5 6 7}

Is the combination of BGB-15025 and Tislelizumab safe for humans?

Tislelizumab has been studied in various cancers and generally has an acceptable safety profile. Common side effects include fatigue, anemia (low red blood cell count), and decreased neutrophil count (a type of white blood cell). Serious side effects can include respiratory infections or failure and liver damage. ^{2 4 5 6 7}

Is the drug BGB-15025, Tislelizumab a promising treatment for advanced cancers?

Yes, Tislelizumab is a promising drug for advanced cancers. It has shown positive effects in treating various types of cancer, including lung, liver, and stomach cancers. It is designed to help the immune system fight cancer more effectively and has been approved for use in several countries. It also offers an economic advantage, making it a valuable option for cancer treatment. ^{2 3 4 5 8}

What makes the drug BGB-15025 + Tislelizumab unique for advanced cancers?

The drug combination of BGB-15025 and Tislelizumab is unique because Tislelizumab is a specially engineered antibody that blocks a protein called PD-1, which helps cancer cells hide from the immune system. This drug is designed to minimize unwanted interactions with other immune cells, potentially making it more effective and safer compared to other similar treatments. ^{2 3 4 5 8}

Research Team

Xiusong Qiu, MD

Principal Investigator

BeiGene

Eligibility Criteria

This trial is for adults with advanced solid tumors, including lung, esophageal, or stomach cancers that have worsened after treatment or haven't been treated yet. They must be relatively healthy (ECOG ≤ 1) and have at least one tumor that can be measured. People who've had prior HPK1-targeted therapy or don't meet specific blood and organ function tests cannot join.

Inclusion Criteria

My blood tests show normal organ function.

I have advanced cancer that cannot be removed by surgery and have either tried other cancer treatments without success or have not received any treatments for my advanced disease.

I have an advanced cancer that cannot be removed by surgery and have not been treated with HPK1-targeting therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive BGB-15025 monotherapy in sequential cohorts of increasing doses to determine the maximum tolerated dose

Up to 3 years

21-day cycles

Dose Expansion

Based on recommended doses, participants receive BGB-15025 alone or in combination with tislelizumab, with or without chemotherapy

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• BGB-15025
• Tislelizumab

Trial Overview The study is testing the safety of a new drug called BGB-15025 alone and when used with Tislelizumab in patients with advanced solid tumors. It aims to find the highest dose patients can take without serious side effects and suggest doses for future Phase 2 trials.

Participant Groups

Group I: Phase 1b: Dose Expansion Experimental Treatment 2 Interventions

Phase 1b dose expansion will begin based upon the recommended doses for expansion (RDFE) for BGB-15025 alone or in combination with tislelizumab, and with or without chemotherapy as determined from Phase 1a

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

Part A: Participants will receive once daily of BGB-15025 monotherapy in sequential cohorts of approximately 7 increasing doses Part B: Participants will receive once daily of BGB-15025 in sequential cohorts plus 200mg tislelizumab on day 1 of each 21-day cycle (combination therapy )

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Findings from Research

An indirect comparison of tislelizumab and pembrolizumab in combination with chemotherapy for advanced NSCLC, involving over 2,000 participants from 6 randomized trials, showed no significant differences in overall survival, progression-free survival, or objective response rates between the two treatments.

Both treatments were associated with a similar risk of severe adverse events, indicating that either tislelizumab or pembrolizumab can be considered effective and safe options for first-line therapy in advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab plus chemotherapy versus pembrolizumab plus chemotherapy for the first-line treatment of advanced non-small cell lung cancer: systematic review and indirect comparison of randomized trials. Guo, Y., Jia, J., Hao, 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]

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 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]

Tislelizumab, an anti-PD-1 monoclonal antibody, showed a confirmed objective response rate of 24% in patients with PD-L1-positive urothelial carcinoma who had progressed after platinum therapy, indicating its efficacy in this challenging patient population.

The treatment had a manageable safety profile, with the most common adverse events being anemia (27%) and pyrexia (19%), and only a small percentage of patients experiencing severe side effects, suggesting that tislelizumab is a viable option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab in Asian patients with previously treated locally advanced or metastatic urothelial carcinoma. Ye, D., Liu, J., Zhou, A., et al.[2022]

In a study of 223 patients with locally advanced/metastatic non-squamous non-small cell lung cancer, 57.4% achieved an objective tumor response when treated with tislelizumab combined with chemotherapy, with a median time to response of 7.9 weeks.

The treatment was generally well tolerated, and responders who achieved deeper tumor shrinkage (greater than 30%) showed a trend toward longer progression-free survival, indicating both efficacy and safety of tislelizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Response characteristics of tislelizumab combined with chemotherapy in first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer]. Lu, S., Yu, XM., Hu, YP., et al.[2023]

Atezolizumab therapy significantly improves overall survival (median OS of 11.2 months) in patients with previously treated advanced non-small cell lung cancer (NSCLC), demonstrating its efficacy in a diverse patient population.

The treatment has a manageable safety profile, with serious adverse events occurring in only 8.0% of patients and no new safety signals identified, indicating it is a viable option for patients often excluded from clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final results from TAIL: updated long-term efficacy of atezolizumab in a diverse population of patients with previously treated advanced non-small cell lung cancer. Ardizzoni, A., Azevedo, S., Rubio-Viqueira, B., et al.[2022]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Tislelizumab plus chemotherapy versus pembrolizumab plus chemotherapy for the first-line treatment of advanced non-small cell lung cancer: systematic review and indirect comparison of randomized trials. [2023]

2. 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]

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

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

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

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

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

Tislelizumab in Asian patients with previously treated locally advanced or metastatic urothelial carcinoma. [2022]

6. China pubmed.ncbi.nlm.nih.gov

[Response characteristics of tislelizumab combined with chemotherapy in first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer]. [2023]

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

Final results from TAIL: updated long-term efficacy of atezolizumab in a diverse population of patients with previously treated advanced non-small cell lung cancer. [2022]

8. 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]