Atezolizumab for Throat Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Mihir Patel, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Emory University

Must not be taking: Immunosuppressants, Immunostimulants, Antivirals, others

Disqualifiers: Autoimmune disease, CNS metastases, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This phase II trial tests how well atezolizumab works in treating patients with human papillomavirus (HPV) related oropharyngeal squamous cell carcinoma that is able to be removed with surgery (resectable). Immunotherapy with atezolizumab, may include changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that patients should not be on certain immunosuppressive medications or systemic immunostimulatory agents before starting the study. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Atezolizumab (Tecentriq) for throat cancer?

Atezolizumab has shown effectiveness in treating various cancers by targeting PD-L1, a protein that helps cancer cells evade the immune system. In head and neck cancer, which includes throat cancer, Atezolizumab has demonstrated clinical activity and safety, suggesting it could be a promising treatment option. ^{1 2 3 4 5}

Is atezolizumab generally safe for humans?

Atezolizumab, also known as Tecentriq, has been approved for use in several cancers, including lung and bladder cancer, with an acceptable safety profile. Common side effects include tiredness, loss of appetite, and nausea, while more serious effects can include lung inflammation, liver inflammation, and thyroid issues. ^{2 6 7 8 9}

What makes the drug atezolizumab unique for treating throat cancer?

Atezolizumab is unique because it is a monoclonal antibody that targets PD-L1, a protein that helps cancer cells evade the immune system, thereby boosting the body's immune response against the tumor. This mechanism of action is different from traditional chemotherapy, which directly targets and kills cancer cells. ^{2 6 8 10 11}

Eligibility Criteria

This trial is for adults over 18 with HPV-related oropharyngeal squamous cell carcinoma that can be surgically removed. Participants must not be pregnant, agree to use contraception, and have no extensive neck lymph node involvement. Those with prior radiation above the clavicles or certain other cancers within two years are excluded.

Inclusion Criteria

My throat cancer is caused by HPV and confirmed by tests.

Serum albumin within normal range

I am 18 years old or older.

Exclusion Criteria

I have high calcium levels in my blood that are causing symptoms.

My kidney function is below the normal range.

I have a history of lung conditions.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 doses of atezolizumab intravenously, with CT and MRI scans, and possible tumor biopsy

6 weeks

Surgery

Participants undergo surgery after receiving treatment with atezolizumab

2 weeks

Follow-up

Participants are monitored for event-free survival and pathologic response, with biomarker analysis

Up to 2 years

Treatment Details

Interventions

• Atezolizumab (Checkpoint Inhibitor)

Trial Overview The study tests Atezolizumab's effectiveness before surgery in patients with resectable HPV-related throat cancer. It examines how this immunotherapy might affect the immune system's response to tumor cells and their ability to spread.

Participant Groups

Group I: Treatment (Atezolizumab) Experimental Treatment 4 Interventions

Patients receive atezolizumab IV while on study. Patients undergo CT scan and MRI throughout the study. Patients may undergo tumor biopsy while on study.

Atezolizumab is already approved in United States, European Union for the following indications:

🇺🇸 Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

🇪🇺 Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Emory University Hospital Midtown Atlanta, GA

Who Is Running the Clinical Trial?

Emory University Lead Sponsor

National Cancer Institute (NCI) Collaborator

Genentech, Inc. Industry Sponsor

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] Head and neck cancer (HNC) has a poor prognosis at advanced stages. Given the immunosuppressive tumor microenvironment in HNC, inhibition of the programmed death-ligand 1/programmed death-1 (PD-L1/PD-1) signaling pathway represents a promising therapeutic approach. Atezolizumab (anti-PD-L1) is efficacious against many tumor types. Here we report the clinical safety and activity from the HNC cohort of the phase Ia PCD4989g clinical trial.

2. New Zealand pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. [2019] Atezolizumab (Tecentriq™)-a monoclonal antibody targeting programmed death ligand 1 (PD-L1 or CD274 antigen)-is being developed by Genentech as treatment for a variety of haematological malignancies and solid tumours. It been approved in the US as a second-line therapy for urothelial carcinoma and is awaiting approval as a second-line therapy for non-small cell lung cancer. This article summarizes the milestones in the development of atezolizumab leading to this first approval for urothelial carcinoma.

3. England pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. [2022] Atezolizumab is a humanised antiprogrammed death-ligand 1 (PD-L1) monoclonal antibody that inhibits PD-L1 and programmed death-1 (PD-1) and PD-L1 and B7-1 interactions, reinvigorating anticancer immunity. We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer.

4. New Zealand pubmed.ncbi.nlm.nih.gov

Nimotuzumab Combined with Induction Chemotherapy and Concurrent Chemoradiotherapy in Unresectable Locally Advanced Hypopharyngeal Carcinoma: A Single Institution Experience in China. [2022] To investigate the curative and adverse effects (AEs) of additional use of nimotuzumab combined with induction chemotherapy and concurrent chemoradiotherapy in unresectable locoregionally advanced hypopharyngeal carcinoma.

5. France pubmed.ncbi.nlm.nih.gov

[Atezolizumab (Tecentriq®): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. [2019] Treatments for patients with metastatic or advanced urothelial carcinomas on progression after first line chemotherapy or unfit for cisplatin are currently limited. Atezolizumab (Tecentriq®) is a monoclonal antibody targeting PD-L1. The first of IMVIGOR 210 phase II trial (NCT02951767) investigated atezolizumab as front line treatment among 119 patients with metastatic urothelial cancer unfit for cisplatin. Response rate was 23% and median overall survival 15.9 months. The second cohort (NCT02108652) included 310 patients whose tumors were progressing after first line platinum-based chemotherapy. Response rate was 15% and median overall survival 7.9 months. Among patients with high PD-L1 expression on infiltrating immune cells (ICs), response rate was 26% and median overall survival 11 months. Atezolizumab was well-tolerated in both cohorts with 66% of treatment-related toxicities including 12% (cohort 1) and 7% (cohort 2) of grade 3-4 adverse events. These results led to an approval by the FDA in United States and the EMA in Europe. In France, atezolizumab was available through an early access agreement by the French National Agency for Medicines and Health Products (ANSM) for patients with metastatic or advanced urothelial carcinomas on progression after first line chemotherapy or unfit for cisplatin. So far, its avaibility in France within the EMA approval is pending its pricing.

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

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. [2022] On October 18, 2016, the FDA approved atezolizumab (TECENTRIQ; Genentech, Inc.) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose disease progressed during or following platinum-containing chemotherapy. Approval was based on demonstration of clinically meaningful improvements in overall survival (OS) and an acceptable safety profile in two randomized clinical trials (OAK and POPLAR). Median OS in OAK, a phase III trial, was 13.8 months [95% confidence interval (CI), 11.8-15.7] in the atezolizumab arm compared with 9.6 months (95% CI, 8.6-11.2) in the docetaxel arm [hazard ratio (HR) = 0.74; 95% CI, 0.63-0.87; P = 0.0004]. Median OS in POPLAR, a phase II trial, was 12.6 months (95% CI, 9.7-16.0) and 9.7 months (95% CI, 8.6-12.0; HR = 0.69; 95% CI, 0.52-0.92) for the atezolizumab and docetaxel arms, respectively. In patients treated with atezolizumab, the most common (≥20%) adverse reactions were fatigue, decreased appetite, dyspnea, cough, nausea, musculoskeletal pain, and constipation; the most common (≥2%) grade 3 to 4 adverse events were dyspnea, pneumonia, hypoxia, hyponatremia, fatigue, anemia, musculoskeletal pain, aspartate aminotransferase increase, alanine aminotransferase increase, dysphagia, and arthralgia. Clinically significant immune-related adverse events for patients receiving atezolizumab included 1.4% incidence each of grade 3 to 4 pneumonitis, hepatitis, colitis, and thyroid disease. Clin Cancer Res; 23(16); 4534-9. ©2017 AACR.

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

Atezolizumab for children and young adults with previously treated solid tumours, non-Hodgkin lymphoma, and Hodgkin lymphoma (iMATRIX): a multicentre phase 1-2 study. [2020] Atezolizumab is an inhibitor of PD-L1, which can lead to enhanced anticancer T-cell activity. We aimed to evaluate the safety, pharmacokinetics, and activity of atezolizumab in children and young adults with refractory or relapsed solid tumours, with known or expected PD-L1 expression.

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

Atezolizumab as the First Systemic Therapy Approved for Alveolar Soft Part Sarcoma. [2023] The objective was to review the pharmacology, efficacy, and safety of atezolizumab (Tecentriq) for the treatment of adult and pediatric patients aged 2 years and older with unresectable or metastatic alveolar soft part sarcoma (ASPS).

9. China pubmed.ncbi.nlm.nih.gov

[Atezolizumab therapy in Chinese patients with locally advanced or metastatic solid tumors: An open-label, phase Ⅰ study]. [2022] To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC).

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

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022] Atezolizumab (Tecentriq, MPDL3280A; Genentech/Roche) is an FcγR binding-deficient, fully humanized IgG1 mAb designed to interfere with the binding of PD-L1 ligand to its two receptors, PD-1 and B7.1. By blocking the PD-L1/PD-1 immune checkpoint, atezolizumab reduces immunosuppressive signals found within the tumor microenvironment and, consequently, increases T-cell-mediated immunity against the tumor. Atezolizumab has been FDA approved as second-line therapy for advanced bladder cancer. This accelerated approval was based on phase II trial data in patients with metastatic bladder cancer that showed unexpected and durable tumor responses. In subjects whose tumors progressed on first-line platinum-based chemotherapy, the objective response rate was 15%, the complete response rate was 5%, and 1-year overall survival was 36%. In subjects that were chemotherapy naïve and cisplatin ineligible, the objective response rate was 24%, the complete response rate was 7%, and 1-year overall survival was 57%. Better responses were associated with higher PD-L1 expression on the tumor-infiltrating leukocytes. These data suggest that patients with advanced bladder cancer treated with atezolizumab have significantly better response rates and survival than historical controls treated with other second-line regimens. The toxicity profile of atezolizumab is also favorable. Trials are currently assessing whether atezolizumab is effective in earlier bladder cancer stages and in the first-line metastatic setting. Clin Cancer Res; 23(8); 1886-90. ©2016 AACR.

11. France pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Previously Treated Advanced Non-Small Cell Lung Cancer. [2020] Atezolizumab (TECENTRIQ™), an immune checkpoint inhibitor, is an immunoglobulin G1 monoclonal antibody that binds to programmed death ligand 1 (PD-L1) and blocks its interactions with programmed death 1 and B7.1 receptors. Atezolizumab is approved as monotherapy in several countries worldwide for the treatment of patients with advanced non-small cell lung cancer (NSCLC) who have previously received chemotherapy. Approval was based on its clinical benefit in this setting in the phase II POPLAR and phase III OAK trials. In these studies, atezolizumab significantly prolonged overall survival (OS) relative to docetaxel, regardless of PD-L1 status. Increasing PD-L1 expression was associated with OS improvements. Atezolizumab also demonstrated efficacy in the phase II FIR and BIRCH trials, as assessed by objective response rates (ORRs) in patients with tumours expressing PD-L1. Higher ORRs were seen in patients with high PD-L1 expression. Atezolizumab had an acceptable, manageable tolerability profile, with a low incidence of immune-related adverse events. Therefore, atezolizumab is a valuable treatment option for patients with advanced NSCLC that has progressed during or after chemotherapy.