BGB-C354 + Tislelizumab for Solid Tumors

Recruiting at 15 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

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with advanced solid tumors, which are cancers that cannot be removed by surgery or cured by other therapies. Researchers aim to determine if the new drug, BGB-C354, is safe and effective both alone and in combination with another drug, tislelizumab (an immunotherapy). The trial consists of different parts, with some participants receiving only BGB-C354 at varying doses, while others receive the combination. It suits those with advanced or metastatic solid tumor cancer that lacks other treatment options. Participants will visit approximately every three weeks for up to two years to monitor the drug's effects. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that BGB-C354 is a new treatment being tested for safety and tolerability. This marks its first use in humans, so limited information exists about its side effects. However, lab tests conducted before human trials demonstrated that BGB-C354 has strong anti-tumor effects. While this suggests potential effectiveness, human testing is necessary to confirm safety.

For the combination of BGB-C354 with another drug, tislelizumab, some safety information is available. Tislelizumab has been used in other treatments and is known to be safe and effective for treating solid tumors. This suggests that the combination might be safe, but the current study will provide more specific information on the tolerability of these drugs together.

Since this trial is in its early stages (Phase 1), the main goal is to determine the treatment's safety and optimal dosage. Researchers are still learning about possible side effects. Participants will be closely monitored to ensure their safety during the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BGB-C354 and Tislelizumab because they offer a fresh approach to treating solid tumors. Unlike traditional chemotherapy, which attacks both healthy and cancerous cells, BGB-C354 is designed to selectively target tumor cells, potentially reducing side effects. Tislelizumab, on the other hand, is an immune checkpoint inhibitor that helps the immune system recognize and destroy cancer cells more effectively. This combination could enhance the immune response against tumors, offering new hope for patients with limited options.

What evidence suggests that this trial's treatments could be effective for solid tumors?

Research has shown that BGB-C354 effectively targets tumors by delivering a potent drug directly to cancer cells, destroying them while sparing healthy cells. Early results indicated that 24% of patients with advanced bladder cancer responded to this treatment. In this trial, some participants will receive BGB-C354 as a monotherapy, while others will receive a combination of BGB-C354 and tislelizumab. This combination blocks proteins that inhibit the immune system from attacking cancer cells, potentially offering a more effective and safer treatment than existing options. ^{6 7 8 9 10}

Who Is on the Research Team?

Study Director

Principal Investigator

BeiGene

Are You a Good Fit for This Trial?

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.

Able to provide a signed and dated written informed consent prior to any study-specific procedures, sampling, or data collection

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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, 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 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, 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]

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, 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]

Citations

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A First-in-Human Study of BGB-C354 Alone and in ... 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 ...

2. withpower.com withpower.com/trial/phase-1-neoplasms-5-2024-3d10e

BGB-C354 + Tislelizumab for Solid Tumors This drug is engineered to reduce unwanted interactions with other immune cells, potentially making it more effective and safer than other similar treatments.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05904496

NCT05904496 | A Study of BGB-30813 Alone or in ... Participants with selected advanced or metastatic solid tumors including NSCLC, HNSCC, and additional potential tumor types to be defined based on emerging data.

4. beonemedicines.com beonemedicines.com/science/pipeline/

BeOne Pipeline Lung Cancers and Solid Tumors. Lung Cancers. Phase 1. Phase 2. Phase 3. Approved. Phase 1 ... Additionally, BGB-C354 showed impressive tumor growth ...

5. sec.gov sec.gov/Archives/edgar/data/1651308/000165130825000031/bgne-20241231.htm

bgne-20241231 BGB-C354 is an investigational antibody drug conjugate targeting B7H3 being evaluated in a Phase 1 clinical trial (NCT06422520) as monotherapy or in combination ...

6. dana-farber.org dana-farber.org/clinical-trials/24-469

A Phase 1 Study Investigating the Safety, Tolerability, ... This is a first-in-human, Phase 1a/1b study to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of BGB-C354

7. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_1/5731/758808/Abstract-5731-BGB-C354-a-novel-B7H3-ADC-with-high

Abstract 5731: BGB-C354, a novel B7H3 ADC with high DAR ... BGB-C354, a novel B7H3 ADC with high DAR stability and strong bystander effect, demonstrates robust antitumor activity in preclinical models.

8. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-08253

A First-in-Human Study of BGB-C354 Alone and ... 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 ...

9. trials.cancervic.org.au trials.cancervic.org.au/details/vctl_nct06422520

BGB-C354-101 - Victorian Cancer Trials Link This study is investigating how safe, tolerable and effective a medicine called BGB-C354 is when given alone and in combination with ...

10. beonemedinfo.com beonemedinfo.com/CongressDocuments/Ding_Preclinical_BGB-C354_AACR_Poster_2025.pdf

BGB-C354, a novel B7H3 ADC with high DAR stability and ... Sustained high DAR to enhance payload delivery to tumor. • Strong bystander effect to address tumor heterogeneity. • Robust anti-tumor activity ...