BGB-C354 + Tislelizumab for Solid Tumors

Recruiting at 14 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: BeiGene

Must not be taking: B7H3-targeted, ADCs with topoisomerase

Disqualifiers: Brain metastasis, Interstitial lung disease, others

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

Compensation: Varies

Number of Visits: 42

62 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a first-in-human, Phase 1a/1b study to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of BGB-C354 alone and in combination with tislelizumab in participants with advanced solid tumors. Study details include: * The study will be conducted in 2 phases: Phase 1a (Monotherapy Dose Escalation and Safety Expansion) and Phase 1b (Dose Expansion). * The visit frequency will be approximately every 21 days during study treatment. * The study duration is estimated to be approximately 5 years.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the drug Tislelizumab for treating solid tumors?

Tislelizumab has shown promising anti-tumor effects in various solid tumors, including lung, liver, and gastric cancers, and has been approved in China for several cancer types. It has demonstrated meaningful clinical benefits, such as a 24% response rate in patients with advanced urothelial carcinoma, and is considered to have a manageable safety profile. ^{1 2 3 4 5}

Is the combination of BGB-C354 and Tislelizumab safe for treating solid tumors?

Tislelizumab, used in various solid tumors, has shown an acceptable safety profile with common side effects like fatigue, anemia (low red blood cell count), and decreased neutrophil count (a type of white blood cell). Serious side effects have included respiratory infections or failure and liver injury, but these are less common. ^{1 2 4 6 7}

How is the drug BGB-C354 + Tislelizumab different from other treatments for solid tumors?

The combination of BGB-C354 and Tislelizumab is unique because Tislelizumab is a modified antibody designed to block a protein called PD-1, which helps cancer cells hide from the immune system. This drug is engineered to reduce unwanted interactions with other immune cells, potentially making it more effective and safer than other similar treatments. ^{1 8 9 10 11}

Research Team

Study Director

Principal Investigator

BeiGene

Eligibility Criteria

This trial is for adults with advanced solid tumors who can consent to the study, have a good performance status (able to carry out daily activities), at least one measurable tumor, available tumor tissue sample, and proper organ function. Women able to have children and nonsterile men must agree to use effective birth control during the study.

Inclusion Criteria

I agree to use effective birth control during and for 4 months after the study.

My cancer is advanced and cannot be removed or cured with treatment.

My organs are functioning well.

Exclusion Criteria

I have previously received B7H3-targeted therapy.

I have previously been treated with a specific type of cancer drug for my condition.

I have not taken any antibiotics, antifungals, or antivirals in the last 14 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1a: Monotherapy Dose Escalation and Safety Expansion

BGB-C354 monotherapy doses at sequentially increasing levels and safety expansion at safe dose levels recommended by the Safety Monitoring Committee

Up to approximately 2 years

Visits approximately every 21 days

Phase 1b: Dose Expansion

BGB-C354 administered at the recommended dose for expansion, alone and in combination with tislelizumab

Up to approximately 2 years

Visits approximately every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• BGB-C354
• Tislelizumab

Trial Overview The safety and potential cancer-fighting effects of BGB-C354 alone or combined with Tislelizumab are being tested in people with advanced solid tumors. The trial has two phases: an initial phase where doses are increased to find safe levels, followed by a phase that expands on these doses.

Participant Groups

Group I: Phase 1b: Part D (Combination Therapy Expansion) Experimental Treatment 2 Interventions

BGB-C354 and tislelizumab will be adminsitered at doses determined by the SMC.

Group II: Phase 1b: Part C (Monotherapy Expansion) Experimental Treatment 1 Intervention

BGB-C354 will be administered at the recommended dose for expansion (RDFE).

Group III: Phase 1a: Part B (Safety Expansion) Experimental Treatment 1 Intervention

Participants will enroll at safe dose levels recommended by the Safety Monitoring Committee (SMC) for further evaluation.

Group IV: Phase 1a: Part A (Monotherapy Dose Escalation) Experimental Treatment 1 Intervention

BGB-C354 monotherapy doses at sequentially increasing levels.

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]

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]

Tislelizumab, an anti-PD-1 monoclonal antibody, shows promising efficacy and a manageable safety profile in treating advanced non-small cell lung cancer (NSCLC), with higher affinity to PD-1 compared to other similar therapies like pembrolizumab and nivolumab.

The drug's unique design minimizes binding to macrophages, potentially reducing resistance to treatment, and ongoing trials are exploring its effectiveness in combination with other therapies, which could enhance its role in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab: an investigational anti-PD-1 antibody for the treatment of advanced non-small cell lung cancer (NSCLC). Liu, SY., Wu, YL.[2022]

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 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]

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]

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]

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 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 study of 115 patients with recurrent or metastatic cervical cancer treated with tislelizumab, the overall response rate was 39.1%, and the median progression-free survival was 19.6 months, indicating promising antitumor activity.

Baseline serum C-reactive protein (CRP) levels and the CRP-to-albumin ratio (CAR) were identified as independent risk factors for predicting the efficacy and prognosis of tislelizumab treatment, with higher levels associated with shorter progression-free and overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab for cervical cancer: A retrospective study and analysis of correlative blood biomarkers. Zheng, X., Gu, H., Cao, X., 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]

References

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

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

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

Tislelizumab: an investigational anti-PD-1 antibody for the treatment of advanced non-small cell lung cancer (NSCLC). [2022]

4. England pubmed.ncbi.nlm.nih.gov

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

5. 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]

6. 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]

7. 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]

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

Tislelizumab: First Approval. [2020]

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

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

10. Switzerland pubmed.ncbi.nlm.nih.gov

Tislelizumab for cervical cancer: A retrospective study and analysis of correlative blood biomarkers. [2023]

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

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