Combination Therapies for Head and Neck Cancer

(VELOCITY-HNSCC Trial)

Recruiting at 24 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

Trial Summary

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.

What data supports the effectiveness of the drug combination of Carboplatin, Domvanalimab, Paclitaxel, and Zimberelimab for head and neck cancer?

Research shows that the combination of paclitaxel and carboplatin is effective in treating head and neck cancer, with a 39% overall response rate in heavily pretreated patients. This suggests that these drugs can be effective components in combination therapies for this type of cancer. ^{1 2 3 4 5}

Is the combination therapy for head and neck cancer safe?

The combination of paclitaxel and carboplatin has been found to have tolerable side effects, with some patients experiencing moderate to severe low white blood cell counts (neutropenia) and nerve damage (neurotoxicity). In another study, a combination of pembrolizumab, carboplatin, and paclitaxel was well tolerated, though some patients experienced moderate to severe anemia, low white blood cell counts, low platelet counts, and high blood pressure. ^{2 6 7 8 9}

How is the combination drug therapy for head and neck cancer unique?

This treatment combines carboplatin and paclitaxel, which are known to be effective in heavily pretreated head and neck cancer patients, with domvanalimab and zimberelimab, which are newer agents that may enhance the immune response against cancer. This combination aims to improve outcomes by using both traditional chemotherapy and novel immunotherapy approaches. ^{2 4 10 11 12}

What is the purpose of this trial?

Master protocol: The main goal of this master clinical study is to evaluate the efficacy and safety of multiple novel combination therapies in participants with head and neck squamous cell carcinoma (HNSCC) in various substudies.

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Substudy-01:Treatment Group A: Domvanalimab (DOM) + Zimberelimab (ZIM) + Platinum-based Chemotherapy Experimental Treatment 4 Interventions

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

Group II: Substudy-01: Treatment Group B: Zimberelimab (ZIM) + Platinum-based Chemotherapy Experimental Treatment 3 Interventions

Participants will receive 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+

Findings from Research

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]

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]

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]

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 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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Phase II trial of a paclitaxel-carboplatin combination in recurrent squamous cell carcinoma of the head and neck. [2017]

2. England pubmed.ncbi.nlm.nih.gov

Effectiveness of paclitaxel and carboplatin combination in heavily pretreated patients with head and neck cancers. [2019]

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

Predictors of outcome with cetuximab and paclitaxel for head and neck squamous cell carcinoma. [2018]

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

Analysis of cell-cycle checkpoint pathways in head and neck cancer cell lines: implications for therapeutic strategies. [2019]

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

Nivolumab Doubles Survival for Patients with HNSCC. [2019]

6. Greece 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. [2023]

7. Switzerland 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. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of pembrolizumab for treating recurrent head and neck squamous cell carcinoma. [2022]

10. Greece pubmed.ncbi.nlm.nih.gov

Radiotherapy with concurrent docetaxel and carboplatin for head and neck cancer. [2018]

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

Head and neck cancer: integrating anti-EGFR treatment with standard therapy. [2018]

12. England 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. [2022]