BGB-15025 + Tislelizumab for Advanced Cancers
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: BeiGene
No Placebo Group
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.
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.13478
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.12348
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.14568
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.
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
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.
I can carry out all my self-care but not work activities.
Treatment Details
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.
2Treatment groups
Experimental Treatment
Group I: Phase 1b: Dose ExpansionExperimental Treatment2 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 EscalationExperimental Treatment2 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 )
Find a clinic near you
Research locations nearbySelect from list below to view details:
Oncology ConsultantsHouston, TX
MD AndersonHouston, TX
One Gustave L Levy PlaceNew York, NY
Icahn School of Medicine At Mount SinaiNew York, NY
More Trial Locations
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Who is running the clinical trial?
BeiGeneLead Sponsor
References
Tislelizumab in Asian patients with previously treated locally advanced or metastatic urothelial carcinoma. [2022]Tislelizumab, an anti-programmed death protein-1 (PD-1) monoclonal antibody, was engineered to minimize binding to the FcγR on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. This single-arm phase 2 trial (NCT04004221/CTR20170071) assessed the safety, tolerability, and efficacy of tislelizumab in patients with PD-L1-positive urothelial carcinoma who progressed during/following platinum-containing therapy and had no prior PD-(L)1 inhibitor treatment. Patients were considered PD-L1 positive if ≥ 25% of tumor/immune cells expressed PD-L1 when using the VENTANA™ PD-L1 (SP263) assay. The primary endpoint was objective response rate by independent review committee. As of September 16, 2019, 113 patients had a median study follow-up time of 9.4 mo. Most patients (76%) had visceral metastases, including 24% with liver and 23% with bone metastases. Among 104 efficacy-evaluable patients, confirmed objective response rate was 24% (95% confidence interval, 16, 33), including 10 complete and 15 partial responses. Median duration of response was not reached. Among 25 responders, 17/25 (68%) had ongoing responses. Median progression-free survival and overall survival times were 2.1 and 9.8 mo, respectively. The most common treatment-related adverse events were anemia (27%) and pyrexia (19%). Anemia (7%) and hyponatremia (5%) were the only grade 3-4 treatment-related adverse events and occurred in ≥ 5% of patients. Three investigator-assessed deaths were considered to be possibly related to study treatment (hepatic failure, n = 2; respiratory arrest, n = 1). Tislelizumab demonstrated meaningful clinical benefits in patients with previously treated locally advanced or metastatic PD-L1-positive urothelial carcinoma and had a manageable safety profile.
Tislelizumab Plus Chemotherapy as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC (RATIONALE 304): A Randomized Phase 3 Trial. [2021]Tislelizumab, an anti-programmed cell death protein-1 antibody, was specifically engineered to minimize FcɣR macrophage binding to abrogate antibody-dependent phagocytosis. Compared with chemotherapy alone, tislelizumab plus chemotherapy may improve clinical outcomes in patients with advanced nonsquamous NSCLC (nsq-NSCLC).
Tislelizumab for Relapsed/Refractory Classical Hodgkin Lymphoma: 3-Year Follow-up and Correlative Biomarker Analysis. [2023]Tislelizumab is an anti-programmed cell death protein 1 (anti-PD-1) monoclonal antibody specifically designed to minimize binding to Fcγ receptors (FcγR).
Tislelizumab: A Modified Anti-tumor Programmed Death Receptor 1 Antibody. [2023]Tislelizumab is an anti-programmed death receptor 1 (PD-1) monoclonal immunoglobulin G 4 antibody developed by BeiGene. The structure of tislelizumab has been modified to maximally inhibit the binding of PD-1 to programmed death ligand 1 (PD-L1) and minimize the binding of tislelizumab to Fcγ receptors. In clinical studies, tislelizumab has shown preliminary anti-tumor effects in various solid tumors, such as Hodgkin's lymphoma, urothelial carcinoma, lung cancer, gastric and esophageal cancer, liver cancer, nasopharyngeal carcinoma, colorectal cancer, and microsatellite instability-high/mismatch repair-deficient tumors. In addition, it also showed new promise in solid tumor treatment in combination with ociperlimab. Due to its satisfactory anti-tumor effects, tislelizumab has received approvals in China for the treatment of classical Hodgkin's lymphoma, urothelial carcinoma, squamous non-small cell lung cancer, non-squamous non-small cell lung cancer, and hepatocellular carcinoma, and it is now under investigation for a new indication in microsatellite instability-high/mismatch repair-deficient tumors. Moreover, it has been granted orphan designations in hepatocellular carcinoma, esophageal cancer, and gastric cancer, including cancer of the gastroesophageal junction, by the US Food and Drug Administration. Tislelizumab has an acceptable safety profile; the most common adverse effects include fatigue, anemia, and decreased neutrophil count, while the most fatal events have been related to respiratory infection or failure, and hepatic injury. Tislelizumab has an economic advantage compared with other well-studied PD-1/PD-L1 inhibitors; thus, the introduction of it could provide clinical oncologists with an effective weapon against tumors and may alleviate the burden of cancer patients.
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]In patients with previously treated advanced or metastatic non-small cell lung cancer (NSCLC), atezolizumab therapy improves survival with manageable safety. The open-label, single-arm phase III/IV TAIL study (NCT03285763) evaluated atezolizumab monotherapy in patients with previously treated NSCLC, including those with Eastern Cooperative Oncology Group performance status of 2, severe renal impairment, prior anti-programmed death 1 therapy, autoimmune disease, and age ≥75 years. Patients received atezolizumab intravenously (1200 mg) every 3 weeks. At data cut-off for final analysis, the median follow-up was 36.1 (range 0.0-42.3) months. Treatment-related (TR) serious adverse events (SAEs) and TR immune-related adverse events (irAEs) were the coprimary endpoints. Secondary endpoints included overall survival (OS), progression-free survival (PFS), overall response rate, and duration of response. Safety and efficacy in key patient subgroups were also assessed. TR SAEs and TR irAEs occurred in 8.0% and 9.4% of patients, respectively. No new safety signals were documented. In the overall population, median OS and PFS (95% CI) were 11.2 months (8.9 to 12.7) and 2.7 months (2.3 to 2.8), respectively. TAIL showed that atezolizumab has a similar risk-benefit profile in clinically diverse patients with previously treated NSCLC, which may guide treatment decisions for patients generally excluded from pivotal clinical trials.
[Response characteristics of tislelizumab combined with chemotherapy in first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer]. [2023]Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.
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]Purpose: Pembrolizumab and tislelizumab have demonstrated significant clinical benefits in first-line treatment for advanced NSCLC. However, no head-to-head clinical trial has ever compared the optimal choice. Therefore, we conducted an indirect comparison to explore the optimal choice for advanced NSCLC combined with chemotherapy. Methods: We conducted a systematic review of randomized trials; the clinical outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). Indirect comparisons between tislelizumab and pembrolizumab were conducted with the Bucher method. Results: Data were abstracted from 6 randomized trials involving more than 2,000 participants. Direct meta-analysis showed that both treatment regimens improved clinical outcomes compared with chemotherapy alone (PFS: hazard ratio (HR)tis+chemo/chemo 0.55, 95% CI 0.45-0.67; HRpem+chemo/chemo 0.53, 95% CI 0.47-0.60; ORR: relative risk (RR)tis+chemo/chemo 1.50, 95% CI 1.32-1.71; RRpem+chemo/chemo 1.89, 95% CI 1.44-2.48). Regarding safety outcomes, tislelizumab and pembrolizumab have a higher risk in the incidence of grade 3 or higher AEs (RRtis+chemo/chemo 1.12, 95% CI 1.03-1.21; RRpem+chemo/chemo 1.13, 95% CI 1.03-1.24). The indirect comparison showed that there was no significant difference between tislelizumab plus chemotherapy and pembrolizumab plus chemotherapy in terms of PFS (HR: 1.04, 95% CI 0.82-1.31), ORR (RR: 0.79, 95% CI 0.59-1.07), the incidence of grade 3 or higher AEs (RR 0.99, 95% CI 0.87-1.12), and AEs leading to death (RR 0.70, 95% CI 0.23-2.09). In progression-free survival subgroup analysis, the results demonstrate no significant differences in PFS by PD-L1 TPS expression level, age, liver metastasis status, and smoking status between tislelizumab plus chemotherapy and pembrolizumab plus chemotherapy. Conclusion: The efficacy and safety of tislelizumab combination chemotherapy were not substantially different from pembrolizumab combination chemotherapy.
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]The aim of this study was to investigate the antitumour activity, safety, and tolerability of pamiparib plus tislelizumab in patients with previously treated advanced solid tumours.