Combination Therapies for Head and Neck Cancer

(VELOCITY-HNSCC Trial)

Recruiting at 31 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Gilead Sciences

Must not be taking: Immune checkpoint inhibitors, Systemic steroids

Disqualifiers: Nasopharyngeal cancer, Active autoimmune, 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: Unknown

Duration: Up to 36 months

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test new combination therapies for head and neck cancer, specifically squamous cell carcinoma in areas like the mouth and throat. Researchers seek to evaluate the effectiveness of domvanalimab (an experimental treatment) and zimberelimab combined with chemotherapy, compared to zimberelimab with chemotherapy alone. Individuals with confirmed head and neck cancer that cannot be cured with local treatments and who have not received systemic therapy for this type of cancer may be suitable candidates. 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 protocol does not specify if you must stop taking your current medications. However, if you are on any non-cancer related medications, such as hormone replacement therapy, you can continue them. If you are taking investigational drugs or certain cancer treatments, you may need to stop them at least 4 weeks before starting the trial.

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

Earlier studies combining domvanalimab and zimberelimab with chemotherapy did not reveal any new safety issues for patients with upper gastrointestinal cancers, indicating that the treatment is generally well-tolerated. Research on zimberelimab alone has shown that serious side effects are rare. For example, in one study, only a few patients experienced severe allergic reactions or lung inflammation.

Both treatments are being tested with common chemotherapy drugs like carboplatin and paclitaxel, which have well-known side effects. As this is a Phase 2 trial, researchers are closely monitoring the safety of these treatments. Current evidence suggests that these treatment combinations could be safe for more people, although side effects can vary from person to person. ^{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 combine innovative immunotherapies with established chemotherapy options. Domvanalimab and Zimberelimab are monoclonal antibodies that help the immune system recognize and attack cancer cells more effectively. This is different from traditional treatments that primarily rely on chemotherapy drugs like paclitaxel and carboplatin to kill cancer cells directly. By adding these immune-boosting drugs, researchers hope to enhance the body's natural defenses, potentially improving outcomes and reducing side effects compared to standard chemotherapy alone.

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

Research has shown that combining domvanalimab (DOM) and zimberelimab (ZIM) with chemotherapy can help treat certain cancers. In this trial, participants in Treatment Group A will receive DOM + ZIM + platinum-based chemotherapy (paclitaxel + carboplatin). Previous studies in patients with advanced gastroesophageal cancer showed that this combination led to tumor shrinkage in more than half of the patients, with a 59% response rate, and patients lived for about 26.7 months on average. Participants in Treatment Group B will receive ZIM + platinum-based chemotherapy. When zimberelimab is used with chemotherapy alone, patients typically experienced about 4.9 months before the cancer worsened. These findings suggest that adding domvanalimab to zimberelimab and chemotherapy might improve results for patients with head and neck cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

Gilead Study Director

Principal Investigator

Gilead Sciences

Are You a Good Fit for This Trial?

This trial is for adults with head and neck squamous cell carcinoma that can't be cured by surgery or radiation. They shouldn't have had systemic therapy for this cancer before, unless it was over 6 months ago after platinum therapy. Participants need at least one measurable tumor and must be fairly active (able to care for themselves).

Inclusion Criteria

I have at least one tumor that can be measured on a scan.

My cancer in the mouth or throat area is confirmed and cannot be cured with surgery or radiation.

I can provide tumor samples for testing, preferably from areas not treated with radiation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either DOM + ZIM + platinum-based chemotherapy or ZIM + platinum-based chemotherapy

Up to 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 36 months

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Domvanalimab
• Paclitaxel
• Zimberelimab

Trial Overview The study tests new combo treatments in sub-studies within a larger trial. It's looking at how well these combos work and their safety. The combinations include Domvanalimab, Zimberelimab, Paclitaxel, and Carboplatin.

How Is the Trial Designed?

Group I: Treatment Group B: Zimberelimab (ZIM) + Platinum-based Chemotherapy Experimental Treatment 3 Interventions

Participants will receive ZIM + platinum-based chemotherapy (paclitaxel + carboplatin).

Group II: Treatment Group A: Domvanalimab (DOM) + Zimberelimab (ZIM) + Platinum-based Chemotherapy Experimental Treatment 4 Interventions

Participants will receive DOM + ZIM + platinum-based chemotherapy (paclitaxel + carboplatin).

Who Is Running the Clinical Trial?

Gilead Sciences

Lead Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Arcus Biosciences, Inc.

Industry Sponsor

Trials

44

Recruited

7,500+

Published Research Related to This Trial

Paclitaxel was found to be more effective than carboplatin in inducing cell death (apoptosis) and inhibiting growth of head and neck squamous cell carcinoma (HNSCC) cells, with its action linked to increased cyclin B1/CDC2 activity and prolonged mitotic arrest.

Combining paclitaxel and carboplatin, either simultaneously or sequentially, resulted in greater inhibition of cell growth compared to using either drug alone, highlighting the potential for enhanced therapeutic strategies in treating HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of cell-cycle checkpoint pathways in head and neck cancer cell lines: implications for therapeutic strategies. Coleman, SC., Stewart, ZA., Day, TA., et al.[2019]

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]

In a phase III trial, patients with head and neck squamous cell carcinoma who were resistant to platinum-based chemotherapy and treated with nivolumab experienced a 30% lower risk of death compared to those receiving standard single-agent chemotherapy.

The 1-year survival rate for patients treated with nivolumab was twice that of those receiving traditional chemotherapy, highlighting its potential as a more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Doubles Survival for Patients with HNSCC. [2019]

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 18 patients with recurrent metastatic head and neck squamous cell carcinoma, the combination of cetuximab and paclitaxel after immune checkpoint inhibitor therapy showed a 44.4% objective response rate and a 72.2% disease control rate, indicating significant efficacy.

The treatment was associated with manageable safety, with some patients experiencing grade 3 adverse events like neutropenia, but no treatment-related deaths occurred, suggesting that this regimen is a viable option for patients who have progressed after ICI therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes of Cetuximab and Paclitaxel after Progression on Immune Checkpoint Inhibitors in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Suzuki, S., Toyoma, S., Kawasaki, Y., et al.[2021]

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 27 patients with recurrent squamous cell carcinoma of the head and neck, the combination of paclitaxel and carboplatin showed an objective response rate of 29.6%, with a median response duration of 4.2 months.

However, the treatment was associated with significant toxicities, including high rates of neutropenia (62.9%) and other severe side effects, indicating a need for safer chemotherapy alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of a paclitaxel-carboplatin combination in recurrent squamous cell carcinoma of the head and neck. Pivot, X., Cals, L., Cupissol, D., et al.[2017]

In a phase II study involving 24 heavily pretreated patients with advanced head and neck cancer, the combination of paclitaxel and carboplatin resulted in an overall response rate of 39%, with 17% achieving a complete response and 22% a partial response.

The treatment was generally tolerable, although 79% of patients experienced neurotoxicity, and some had significant neutropenia, indicating that while effective, careful monitoring of side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of paclitaxel and carboplatin combination in heavily pretreated patients with head and neck cancers. Stathopoulos, GP., Rigatos, S., Papakostas, P., et al.[2019]

In a study involving 16 patients with head and neck cancer, the combination of docetaxel and carboplatin during radiotherapy resulted in a high complete response rate of 81%, indicating strong efficacy in treating this type of cancer.

While the treatment was effective, it also led to significant toxicities, including grade 3 mucositis in 69% of patients, highlighting the need for careful management of side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy with concurrent docetaxel and carboplatin for head and neck cancer. Karasawa, K., Shinoda, H., Katsui, K., et al.[2018]

In a study of 49 patients with recurrent or metastatic head and neck cancer, the combination of paclitaxel and carboplatin showed a 57% overall response rate in patients with nasopharyngeal cancer, indicating significant efficacy for this specific type of cancer.

The treatment was generally well tolerated, with only low rates of severe toxicities, suggesting it can be safely administered as an outpatient therapy, although its effectiveness was only moderate in non-nasopharyngeal cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel by three-hour infusion and carboplatin in advanced carcinoma of nasopharynx and other sites of the head and neck. A phase II study conducted by the Hellenic Cooperative Oncology Group. Fountzilas, G., Skarlos, D., Athanassiades, A., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06727565

NCT06727565 | Study of Novel Treatment Combination ... The primary objective is to assess the efficacy of DOM and ZIM in combination with chemotherapy versus ZIM in combination with chemotherapy. Detailed ...

2. targetedonc.com targetedonc.com/view/domvanalimab-combo-shows-enriched-first-line-efficacy-in-advanced-gi-cancers

Domvanalimab Combo Shows Enriched First-Line Efficacy ... The combination of domvanalimab and zimberelimab showed a 59% objective response rate in advanced HER2-negative gastroesophageal cancer patients ...

3. investors.arcusbio.com investors.arcusbio.com/investors-and-media/press-releases/press-release-details/2025/Anti-TIGIT-Domvanalimab-Plus-Anti-PD-1-Zimberelimab-and-Chemotherapy-Showed-26-7-Months-of-Median-Overall-Survival-as-First-Line-Treatment-of-Unresectable-or-Advanced-Gastroesophageal-Adenocarcinomas-in-the-Phase-2-EDGE-Gastric-Study/default.aspx

Anti-TIGIT Domvanalimab Plus Anti-PD-1 Zimberelimab ... Anti-TIGIT Domvanalimab Plus Anti-PD-1 Zimberelimab and Chemotherapy Showed 26.7 Months of Median Overall Survival as First-Line Treatment of ...

4. onclive.com onclive.com/view/domvanalimab-plus-zimberelimab-and-chemo-set-for-phase-3-study-after-showing-efficacy-in-untreated-upper-gi-cancers

Domvanalimab Plus Zimberelimab and Chemo Set for ... “[Data from] the study showed a very high response rate of 59% in the overall population, [which included] patients with a PD-L1 TAP of less ...

5. gileadclinicaltrials.com gileadclinicaltrials.com/study?nctid=NCT06727565

Study of Novel Treatment Combination Therapies in ... Master protocol: The main goal of this master clinical study is to evaluate the efficacy and safety of multiple novel combination therapies in ...

6. cancer.gov cancer.gov/clinicaltrials/NCI-2025-00832

Study of Novel Treatment Combination Therapies in ... Substudy-01 will evaluate the efficacy and safety of novel combination of treatment regimens, domvanalimab (DOM) and zimberelimab (ZIM) combined with ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS9141

STAR-121: A phase 3, randomized study of domvanalimab ... STAR-121 is a phase 3, global, open-label, randomized study to evaluate the safety and efficacy of DOM and ZIM plus chemotherapy vs pembro plus chemotherapy as ...