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

Trial Summary

What is the purpose of this trial?

To determine the effect of neoadjuvant atezolizumab alone or in combination with other immune modulating agents on T-cell infiltration in advanced SCCHN. To determine the impact of neo-adjuvant immunotherapy on surgical outcomes.

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.

What data supports the effectiveness of the drug Atezolizumab for head and neck cancers?

Research shows that Atezolizumab, which blocks a protein that helps cancer cells hide from the immune system, has been effective in treating various types of tumors, including head and neck cancer, by improving the body's immune response against the cancer. ^{1 2 3 4 5}

Is atezolizumab safe for use in head and neck cancer treatment?

Atezolizumab has been studied for safety in head and neck cancer, showing it is generally safe for use in humans, with manageable side effects. ^{1 5 6 7 8}

How does the drug used in preoperative immunotherapy for head and neck cancers differ from other treatments?

The drug used in preoperative immunotherapy for head and neck cancers may involve biologics like Omalizumab, which is unique because it targets IgE (a type of antibody involved in allergic reactions) and has been used in other conditions like asthma and allergic rhinitis to reduce symptoms by lowering IgE levels. This approach is different from traditional cancer treatments that typically focus on directly targeting cancer cells. ^{9 10 11 12 13}

Research Team

Alain Algazi, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

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 active hepatitis B or C.

I have severe heart failure (NYHA class III or higher).

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

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety and clinical activity of atezolizumab in head and neck cancer: results from a phase I trial. [2022]

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

Neoadjuvant immunotherapy prior to surgery for mucosal head and neck squamous cell carcinoma: Systematic review. [2022]

3. United States 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. [2021]

4. Greece pubmed.ncbi.nlm.nih.gov

Real-world Data of Palliative First-line Checkpoint Inhibitor Therapy for Head and Neck Cancer. [2023]

5. England pubmed.ncbi.nlm.nih.gov

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

6. England 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. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Induction chemotherapy combined with immunotherapy in locally advanced head and neck squamous cell carcinoma. [2021]

8. England 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. [2023]

9. Italy pubmed.ncbi.nlm.nih.gov

Biologics in allergic rhinitis. [2023]

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

Efficacy and Safety of Ragweed SLIT-Tablet in Children with Allergic Rhinoconjunctivitis in a Randomized, Placebo-Controlled Trial. [2021]

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

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

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

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

13. Germany pubmed.ncbi.nlm.nih.gov

Anti-IgE: A treatment option in allergic rhinitis? [2021]