Tislelizumab + Investigational Agents for Head and Neck Cancer

Recruiting at 92 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: BeiGene

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Nasopharynx carcinoma, Active malignancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: Up to approximately 3 years and 6 months

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of a drug called tislelizumab, both alone and with other new treatments, for squamous cell carcinoma, a type of head and neck cancer that has recurred or spread. The trial includes different groups: some receive only tislelizumab, while others receive it with various combinations of investigational agents. Suitable candidates for this trial have a confirmed diagnosis of head and neck cancer that cannot be treated with local therapies, have not received other drug treatments for their cancer, and have at least one measurable tumor. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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 trial coordinators or your doctor.

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

Research shows that patients generally tolerate the combination of tislelizumab and LBL-007 well. In earlier studies with patients who had advanced cancers, this combination proved safe. Side effects were manageable, making the treatment suitable for those with recurring or spreading cancers.

For the combination of tislelizumab and BGB-A425, studies also suggest good tolerance. Patients experienced expected side effects, usually mild to moderate, indicating the treatment's safety.

The triple combination of tislelizumab, BGB-A425, and LBL-007 has been tested in patients with advanced cancer. Results show that this mix is safe, with mostly manageable side effects, supporting its use in trials like the one under consideration.

In summary, previous studies have shown the treatments tested in the trial to be safe. While side effects can occur, they are usually not severe. Joining the trial could provide access to promising treatments that have been well-tolerated in the past. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for head and neck cancer because they offer new ways to tackle the disease. Tislelizumab is an immunotherapy drug that targets the PD-1 pathway, helping the immune system better recognize and attack cancer cells. This is different from traditional chemotherapy, which directly kills cancer cells but can also harm healthy cells. The investigational agents BGB-A425 and LBL-007 are designed to enhance the effects of Tislelizumab by targeting other pathways involved in cancer growth. Together, these combinations could provide more effective and less harmful treatment options for patients.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

Research shows that tislelizumab may help treat head and neck cancer. In earlier studies, tislelizumab led to better patient outcomes. This trial will explore different treatment combinations. One group will receive Tislelizumab with LBL-007, which proved effective and safe for patients with advanced cancer in previous studies. Another group will test Tislelizumab with BGB-A425, as adding BGB-A425 increased the immune response in lab tests, suggesting it might enhance treatment effectiveness. Additionally, the combination of Tislelizumab, BGB-A425, and LBL-007 is being tested in another group to see if it can further improve treatment results for head and neck cancer. ^{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 head and neck squamous cell carcinoma that hasn't spread too far or been treated systemically in the recurrent/metastatic setting. They must have a certain level of PD-L1 protein expression, at least one tumor measurable by RECIST v1.1 standards, good physical functioning, and proper organ function. Participants can't join if they've had certain other cancers recently, severe lung issues, previous treatments with specific immunotherapies, or serious allergic reactions to similar drugs.

Inclusion Criteria

My cancer tests positive for PD-L1.

Have at least 1 measurable lesion as defined per RECIST v1.1

My cancer is in my throat, mouth, or voice box.

Exclusion Criteria

My cancer is a recurring or spreading type, originating from the nasopharynx, skin, salivary gland, or is a mucosal melanoma.

I have previously been treated with drugs that target the immune system.

I've had severe allergic reactions to certain medications or serious side effects from immune therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Tislelizumab and investigational agents as an infusion every 3 weeks

Up to approximately 3 years and 6 months

Infusion every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Investigational Agent
• Tislelizumab

Trial Overview The study tests the effectiveness and safety of tislelizumab alone or combined with experimental drugs (BGB-A425 or LBL-007) in treating first-line recurrent or metastatic head and neck cancer. It aims to see how well these combinations work compared to current standard treatments.

How Is the Trial Designed?

Group I: Tislelizumab + LBL-007 Experimental Treatment 2 Interventions

Tislelizumab 200 mg administered once every 3 weeks with LBL-007

Group II: Tislelizumab + BGB-A425 + LBL-007 Experimental Treatment 3 Interventions

Tislelizumab 200 mg administered once every 3 weeks with BGB-A425 and LBL-007

Group III: Tislelizumab + BGB-A425 Experimental Treatment 2 Interventions

Tislelizumab 200 mg administered once every 3 weeks with BGB-A425

Group IV: Tislelizumab Active Control 1 Intervention

Tislelizumab 200 milligrams (mg) administered once every 3 weeks

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Published Research Related to This Trial

In a study involving 133 patients with locally advanced squamous cell carcinoma of the head and neck, pembrolizumab combined with radiotherapy did not show a significant improvement in locoregional control or survival compared to the standard treatment of cetuximab with radiotherapy.

However, patients receiving pembrolizumab experienced significantly lower toxicity, with only 74% reporting severe adverse events compared to 92% in the cetuximab group, suggesting it may be a safer option for patients unfit for high-dose cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial. Tao, Y., Biau, J., Sun, XS., et al.[2023]

Pembrolizumab, a PD-1 inhibitor, has shown significant overall response rates and survival benefits in patients with recurrent or metastatic head and neck squamous cell carcinoma compared to chemotherapy alone, particularly in populations with high PD-L1 expression (CPS ≥ 20 and CPS ≥ 1).

The safety profile of pembrolizumab is comparable to other PD-1/PD-L1 inhibitors, with common side effects including diarrhea and hypothyroidism, but it has a favorable toxicity profile compared to the EXTREME chemotherapy regimen, highlighting the importance of PD-L1 scoring for patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of pembrolizumab for treating recurrent head and neck squamous cell carcinoma. Desilets, A., Soulières, D.[2022]

Pembrolizumab, an immune checkpoint inhibitor, has been approved by the FDA for treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), offering a new option with potentially improved efficacy compared to traditional chemotherapy and EGFR inhibitors.

This review discusses the pharmacology and tolerability of pembrolizumab, emphasizing its mechanism of action by blocking the PD-1 receptor, which may enhance the immune response against HNSCC tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. Sheth, S., Weiss, J.[2019]

In a study of adult patients with metastatic head and neck squamous cell cancer, substituting 5-fluorouracil (5-FU) with a taxane in a pembrolizumab-based treatment regimen did not increase toxicity or worsen survival outcomes.

Patients receiving the taxane combination experienced significantly lower rates of mucositis and elevated creatinine levels compared to those on the 5-FU regimen, indicating a better safety profile for the taxane approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety outcomes of pembrolizumab with platinum agent chemotherapy combined with 5-fluorouracil or taxane derivative in head and neck cancer. Lee, B., Chehab, SS., Fan, W., et al.[2023]

In a study of 14 heavily pretreated patients with recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC), the combination of pembrolizumab and lenvatinib showed an objective response rate of 28.6%, indicating potential efficacy even in patients who had previously failed anti-PD-1 therapy.

The disease control rate was 42.9%, with an overall survival of 6.2 months and progression-free survival of 4.6 months, suggesting that this combination therapy may provide meaningful benefits for patients who have limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of pembrolizumab and lenvatinib is a potential treatment option for heavily pretreated recurrent and metastatic head and neck cancer. Chen, TH., Chang, PM., Yang, MH.[2021]

In a small retrospective study of 10 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, the combination of pembrolizumab with carboplatin and paclitaxel (pembro + CP) was well tolerated, with 100% of patients experiencing mild adverse events and 30% experiencing more severe side effects.

The overall response rate (ORR) was 14% with one complete response, and the disease control rate (DCR) was 43%, indicating that while the treatment showed some effectiveness, further prospective studies are needed to fully evaluate its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and preliminary activity of pembrolizumab-carboplatin-paclitaxel in heavily pretreated and/or fragile patients with PDL1-positive recurrent/metastatic head and neck cancer. Cabezas-Camarero, S., Merino-Menéndez, S., Cabrera-Martín, MN., et al.[2023]

In a study of 78 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, treatment with immune checkpoint inhibitors (CPI), either alone or combined with chemotherapy, showed a median progression-free survival (PFS) of 4 months and a median overall survival (OS) of 11 months, indicating the treatment's effectiveness.

The overall response rate was 20.5% and the disease control rate was 46.1%, with the safety profile of immune-related adverse events being consistent with existing data, supporting the use of CPI therapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world Data of Palliative First-line Checkpoint Inhibitor Therapy for Head and Neck Cancer. Wagner, SM., Magnes, T., Melchardt, T., et al.[2023]

PD-1 inhibitors significantly improve overall survival in patients with recurrent or metastatic head and neck cancer compared to standard treatments, with a relative risk of death reduced by 40%.

Patients with human papillomavirus (HPV) positive head and neck cancer showed better response rates to PD-1/PD-L1 inhibitors than those who are HPV negative, indicating that HPV status may influence treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects and safety of PD-1/PD-L1 inhibitors on head and neck cancer: A systematic review and meta-analysis. Wang, BC., Cao, RB., Li, PD., et al.[2021]

In a phase Ia clinical trial involving 32 patients with advanced head and neck cancer, atezolizumab demonstrated a tolerable safety profile, with 66% of patients experiencing treatment-related adverse events, but no grade 5 events reported.

The treatment showed promising efficacy, with 22% of patients achieving objective responses and a median overall survival of 6.0 months, indicating potential benefits regardless of HPV status or PD-L1 expression levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and clinical activity of atezolizumab in head and neck cancer: results from a phase I trial. Colevas, AD., Bahleda, R., Braiteh, F., et al.[2022]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10928599/

A real-world evaluation of tislelizumab in patients with ... The initial results showed tislelizumab was a promising effective and safe drug for HNSCC and NPC.

2. nature.com nature.com/articles/s41467-025-63978-y

Neoadjuvant tislelizumab with afatinib for locally advanced ... The estimated 12-month disease-free survival (DFS) rate, cancer-specific survival (CSS) rate, and OS rate were 84.8% (95% CI: 70.4%–100%), 90.2% ...

3. ema.europa.eu ema.europa.eu/en/medicines/human/EPAR/tevimbra

Tevimbra | European Medicines Agency (EMA) After around 36 months, 32% of those who had Tevimbra had a worsening or recurrence of the cancer or had died compared with 43% of those given placebo (a dummy ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e18034

An exploratory study of neoadjuvant tislelizumab combined ... Results: Between February 2023 and November 2024, 20 pts were enrolled. Median age was 44.5 (18-71) yrs, and 80% male. All pts completed ...

5. targetedonc.com targetedonc.com/view/european-commission-approves-tislelizumab-for-neoadjuvant-adjuvant-nsclc

European Commission Approves Tislelizumab for ... This randomized, double-blind, placebo-controlled study demonstrated a statistically significant and clinically meaningful OS benefit for the ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05909904

NCT05909904 | A Study of Tislelizumab in Combination ... This study is designed to evaluate the efficacy and safety of tislelizumab and tislelizumab in combination with investigational agent(s) in first-line recurrent ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03744468

NCT03744468 | Study of BGB-A425 and LBL-007 in ... This is an open-label, multicenter, nonrandomized Phase 1 and 2 clinical trial evaluating various combinations of BGB-A425 and/or LBL-007 with tislelizumab.

8. clinicaltrials.eu clinicaltrials.eu/trial/study-of-bgb-a425-lbl-007-and-tislelizumab-for-patients-with-advanced-head-and-neck-cancer-lung-cancer-or-kidney-cancer/

Study of BGB-A425, LBL-007, and Tislelizumab for Patients ... This clinical trial tests the effectiveness and safety of BGB-A425, LBL-007, and Tislelizumab in treating advanced Head and Neck Squamous Cell Cancer, ...

9. beonemedinfo.com beonemedinfo.com/CongressDocuments/Desai%20BGB-900-102%20ASCO%202020%20Poster.pdf

bgb-a425, an investigational anti-tim-3 monoclonal ... In vitro evidence demonstrated that combining BGB-A425 with tislelizumab significantly increased IFN-γ production compared with. BGB-A425 or tislelizumab ...

10. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2019-00104

Study of BGB-A425 and LBL-007 in Combination With ... This is an open-label, multicenter, nonrandomized Phase 1 and 2 clinical trial evaluating various combinations of BGB-A425 and/or LBL-007 with tislelizumab.