Preoperative Immunotherapy for Head and Neck Cancers

Overseen By UCSF HDFCCC Cancer Immunotherapy Program (CIP)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alain Algazi

Must not be taking: Immunosuppressants, Steroids, Monoclonal antibodies, others

Disqualifiers: Immunodeficiency, Active infection, Autoimmune disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 44

55 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how atezolizumab, an immunotherapy, either alone or with other drugs, can treat advanced head and neck cancers, specifically squamous cell carcinoma of the head and neck (SCCHN). The researchers aim to determine if these treatments can improve the body's immune response and enhance surgical outcomes. Treatment groups include atezolizumab alone or combined with other drugs like tiragolumab and tocilizumab. Individuals with surgically removable SCCHN who are willing to undergo a biopsy might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer treatment.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive therapy, you may need to stop or adjust these medications before starting the trial. It's best to discuss your specific medications with the trial team.

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

Previous studies have shown that atezolizumab has a tolerable safety profile in patients with advanced head and neck cancers, meaning most can handle the treatment without severe side effects. Researchers found it effective against cancer, even in heavily pre-treated patients.

The combination of atezolizumab and tiragolumab was also studied and well-tolerated, with no major safety issues reported, suggesting that adding tiragolumab does not increase side effects.

Atezolizumab combined with tocilizumab has been tested as well. Atezolizumab alone was well-tolerated, and tocilizumab has been used safely for other conditions, suggesting the combination might also be safe.

Overall, these treatments have demonstrated good tolerability in patients, with no new safety concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer new ways to tackle head and neck cancers by leveraging the immune system. Atezolizumab is an immunotherapy drug that boosts the body's immune response against cancer cells. When combined with Tiragolumab, it targets two different checkpoints in the immune system, potentially enhancing the body's ability to fight the cancer more effectively than current standard treatments like chemotherapy and radiation. The addition of Tocilizumab, an anti-inflammatory drug, could reduce treatment-related side effects, making it a promising combination for improving patient outcomes. These innovative approaches could lead to more effective and less toxic treatment options for patients with head and neck cancers.

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

In this trial, participants will receive different treatment combinations to evaluate their effectiveness for head and neck cancer. Research has shown mixed results for atezolizumab when used alone; some studies found it did not significantly improve survival rates or slow disease progression compared to a placebo. In this trial, some participants will receive atezolizumab monotherapy. Others will receive a combination of atezolizumab and tiragolumab, which has shown evidence of better outcomes, including improved response rates and longer periods without disease worsening. Another group will receive atezolizumab combined with tocilizumab, although less information is available on this combination. Atezolizumab has generally shown promise for its safety and effectiveness in head and neck cancers. Overall, these treatments aim to enhance the immune system's ability to fight cancer. ^{2 5 6 7 8}

Who Is on the Research Team?

Alain Algazi, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

Adults with suspected squamous cell carcinoma of the head and neck (SCCHN) that can be surgically removed. They must have good organ function, not be pregnant or breastfeeding, agree to use contraception, and have no recent cancer treatments or severe allergies to trial drugs. Excluded are those with active cancers elsewhere, certain heart conditions, immune diseases requiring treatment in the last 2 years, infections needing hospitalization recently, COPD stage 2+, known HIV without stable treatment or other conditions that may affect trial safety.

Inclusion Criteria

Be willing and able to provide written informed consent/assent for the trial

Female subject of childbearing potential should have a negative urine or serum pregnancy within 7 days prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

I agree to let my biopsy, taken within the last 3 months or a new one, be used for research.

Exclusion Criteria

I have not received a live vaccine recently and do not plan to during the study.

I have not had major surgery recently.

I am aware of restrictions on certain medications I can take.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive neoadjuvant atezolizumab alone or in combination with other immune-modulating agents for up to 15 days prior to definitive surgery

2 weeks

2 infusions (in-person)

Surgery and Radiation

Participants undergo definitive surgery followed by radiation therapy

Varies based on individual treatment plans

Adjuvant Treatment

For the first 9 participants in Arm A, adjuvant atezolizumab is administered every 3 weeks for up to 12 courses starting 16 weeks after surgery and radiation

36 weeks

12 infusions (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Visits at 30 days post-surgery, 3 months, 6 months, 12 months, and 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Tiragolumab
• Tocilizumab

Trial Overview

The study is testing if pre-surgery immunotherapy with atezolizumab alone or combined with tocilizumab or tiragolumab can increase T-cell infiltration in SCCHN tumors. It also examines how these treatments affect surgery outcomes. Participants will receive one of these drug combinations before their scheduled surgery.

How Is the Trial Designed?

Group I: Atezolizumab Monotherapy Experimental Treatment 1 Intervention

Participants will receive 840mg of atezolizumab over 15 days prior to definitive surgery.

Group II: Atezolizumab + Tocilizumab Experimental Treatment 2 Interventions

Participants will receive 840 mg of atezolizumab IV and 6 mg/kg of Tocilizumab during the 15-day neoadjuvant period prior to definitive surgery.

Group III: Atezolizumab + Tiragolumab Experimental Treatment 2 Interventions

Participants will receive 840 mg of atezolizumab IV and 600 mg of Tiragolumab during the 15-day neoadjuvant period prior to definitive surgery.

Group IV: Atezolizumab (Adjuvant) Experimental Treatment 1 Intervention

Participants will receive 840mg of atezolizumab over 15 days prior to definitive surgery. The first 9 participants in Arm A (atezolizumab monotherapy) will also receive adjuvant atezolizumab 16 weeks after standard of care surgery and radiation, or chemoradiation therapy, at a fixed dose of 1200 mg IV every 3 weeks for an additional 12 cycles.

Who Is Running the Clinical Trial?

Alain Algazi

Lead Sponsor

Trials

2

Recruited

60+

American Head and Neck Society

Collaborator

Trials

2

Recruited

330+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

Omalizumab, a humanized Anti-IgE monoclonal antibody, has been shown to significantly improve symptoms of allergic rhinitis by reducing the need for antiallergic medications and is effective in patients undergoing specific immunotherapy.

Dupilumab, an Anti-IL-4/IL-13 biologic, significantly enhances quality of life in patients with perennial allergic rhinitis, as indicated by improved scores on the sino-nasal Outcome Test (SNOT-22).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologics in allergic rhinitis. Bayar Muluk, N., Cingi, C.[2023]

In a study involving 1025 children aged 5 to 17 with ragweed pollen-induced allergic rhinitis and/or conjunctivitis, the ragweed sublingual immunotherapy (SLIT) tablet significantly reduced allergy symptoms and the need for medication during peak pollen season by 38.3% compared to placebo.

The SLIT tablet was well tolerated, with no reports of severe allergic reactions or anaphylaxis, indicating a favorable safety profile for children undergoing this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Ragweed SLIT-Tablet in Children with Allergic Rhinoconjunctivitis in a Randomized, Placebo-Controlled Trial. Nolte, H., Bernstein, DI., Nelson, HS., et al.[2021]

In a phase 3 study involving 495 patients with recurrent or metastatic head-and-neck squamous cell carcinoma, pembrolizumab demonstrated a median overall survival of 8.4 months, compared to 6.9 months for standard-of-care treatments, indicating a significant improvement in survival rates.

Pembrolizumab was associated with fewer severe treatment-related adverse events (13%) compared to standard-of-care therapies (36%), suggesting a better safety profile for patients receiving pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Cohen, EEW., Soulières, D., Le Tourneau, C., et al.[2019]

Omalizumab, a monoclonal anti-IgE antibody, has been shown to be effective in treating moderate-to-severe allergic asthma and allergic rhinitis, particularly benefiting patients with more severe asthma.

The treatment is well tolerated with a good safety profile, demonstrating anti-inflammatory effects in allergic conditions, which highlights the role of IgE in allergic diseases and supports its use as a therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting immunoglobulin E as a novel treatment for asthma. Sandström, T.[2022]

In a study of 163 patients with locally advanced head and neck squamous cell carcinoma, the combination of sintilimab with induction chemotherapy resulted in a significantly higher objective response rate (84.6% vs 68.4%) compared to induction chemotherapy alone.

Patients receiving the combination treatment also experienced a longer progression-free survival (44% vs 27% at 2 years), while the addition of sintilimab did not significantly increase the rate of severe toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction chemotherapy combined with immunotherapy in locally advanced head and neck squamous cell carcinoma. Li, X., Fang, Q., Du, W., et al.[2021]

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]

A systematic review of clinical trials shows that omalizumab, an anti-IgE antibody, is effective in controlling symptoms of allergic rhinitis (AR) and has a favorable safety profile.

Omalizumab also helps manage comorbid conditions associated with AR, making it a promising treatment option, although it currently lacks an approved license for use in AR in Germany.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-IgE: A treatment option in allergic rhinitis? Pfaar, O., Gehrt, F., Li, H., et al.[2021]

Omalizumab, a humanized monoclonal antibody targeting IgE, effectively reduces allergic symptoms in seasonal allergic rhinitis by lowering free IgE levels, as confirmed by clinical trials involving various patients.

This treatment has a favorable safety profile, allowing for re-treatment in subsequent pollen seasons with minimal risk of adverse events and does not induce acute anaphylaxis, making it a promising option for managing allergic rhinitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience with monoclonal antibodies in allergic mediated disease: seasonal allergic rhinitis. Casale, TB.[2019]

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]

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]

Neoadjuvant immunotherapy targeting the PD-1/PD-L1 axis in head and neck cancer has shown a favorable overall objective response rate of 45.9% across eight clinical trials involving 260 patients.

Importantly, there were no deaths reported due to immune-related toxicities, indicating that this treatment approach is not only effective but also safe in the neoadjuvant setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant immunotherapy prior to surgery for mucosal head and neck squamous cell carcinoma: Systematic review. Amin, N., Maroun, CA., El Asmar, M., et al.[2022]

In a phase Ib/III trial involving 36 patients with recurrent or metastatic head and neck squamous cell carcinoma, the combination of talimogene laherparepvec (T-VEC) and pembrolizumab showed a tolerable safety profile, with only one reported dose-limiting toxicity (fatal arterial hemorrhage) and no other treatment-related fatalities.

The combination therapy resulted in a confirmed partial response in 13.9% of patients, with median progression-free survival of 3.0 months and overall survival of 5.8 months, indicating that its efficacy was comparable to pembrolizumab alone based on historical data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talimogene Laherparepvec and Pembrolizumab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (MASTERKEY-232): A Multicenter, Phase 1b Study. Harrington, KJ., Kong, A., Mach, N., et al.[2021]

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]

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