Radiotherapy + Atezolizumab for Squamous Cell Carcinoma

Recruiting in Duarte (>99 mi)

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Immunosuppressants, PD1 inhibitors

Disqualifiers: Interstitial lung disease, Autoimmune disorders, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 20

Duration: 9 weeks

12 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial tests the safety and side effects radiotherapy in combination with atezolizumab in treating patients with cutaneous squamous cell cancer that has spread to nearby tissue or lymph nodes (locally advanced) and can be removed from surgery (resectable) or cannot be remove by surgery (unresectable). Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving radiotherapy in combination with atezolizumab may help improve outcomes for remission (cancer that is under control) than taking either treatment separately.

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the drug Atezolizumab for treating squamous cell carcinoma?

Atezolizumab has shown effectiveness in treating other cancers like bladder cancer and non-small cell lung cancer by enhancing the immune system's ability to fight tumors, with significant improvements in response rates and survival. Additionally, combining Atezolizumab with stereotactic ablative radiotherapy (SABR) has shown early positive responses in lung cancer patients, suggesting potential benefits for other cancers. ^{1 2 3 4 5}

Is the combination of radiotherapy and atezolizumab safe for humans?

The combination of atezolizumab and stereotactic ablative radiotherapy (SABR) has been studied in patients with early-stage non-small cell lung cancer and was found to be well tolerated, with the full dose of atezolizumab being safe. Atezolizumab alone has been used safely in various cancers, including small cell lung cancer and bladder cancer, with common side effects like rash and hypothyroidism, but no new safety concerns were identified when combined with other treatments. ^{1 3 5 6 7}

How is the treatment of radiotherapy plus atezolizumab unique for squamous cell carcinoma?

This treatment combines atezolizumab, an immune checkpoint inhibitor that boosts the body's immune response against cancer, with stereotactic body radiation therapy (SABR), which precisely targets tumors with high doses of radiation. This combination aims to enhance the effectiveness of treatment by using the body's immune system alongside targeted radiation, which is a novel approach compared to traditional treatments. ^{1 2 3 5 8}

Research Team

Arya Amini

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

Adults with advanced cutaneous squamous cell carcinoma (cSCC) that is borderline resectable or unresectable, and possibly with a few sites of metastasis. Participants must have measurable disease, adequate organ function, no severe allergies to monoclonal antibodies like atezolizumab, not be on certain medications including immunosuppressants recently, and women must not be pregnant or breastfeeding.

Inclusion Criteria

Absolute neutrophil count (ANC) >= 1.0 x 10^9/L

Platelet count >= 75 x 10^9/L

Serum albumin 25 g/L

Exclusion Criteria

Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation

I have had another type of cancer.

I have or had an autoimmune or inflammatory disorder.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiotherapy

Patients undergo stereotactic body radiation therapy (SBRT) on days 1, 3, 5, 7, and 9 of cycle 1

1 week

5 visits (in-person)

Treatment

Patients receive atezolizumab intravenously (IV) beginning 1-2 days after SBRT, repeating every 3 weeks for 3 cycles

9 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Every 12 weeks

Treatment Details

Interventions

• Atezolizumab
• Stereotactic Body Radiation Therapy

Trial Overview The trial is testing the combination of radiotherapy with an immunotherapy drug called Atezolizumab in patients with locally advanced cSCC. The goal is to see if this combo can better control cancer than when each treatment is used alone.

Participant Groups

Group I: Treatment (SBRT, atezolizumab) Experimental Treatment 2 Interventions

Patients undergo SBRT on days 1, 3, 5, 7, and 9 of cycle 1. Beginning 1-2 days after SBRT, patients also receive atezolizumab IV on day 1. Treatment repeats every 3 weeks for 3 cycles in the absence of disease progression or unacceptable toxicity.

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

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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 I study involving 20 patients with early-stage non-small cell lung cancer, the combination of stereotactic ablative radiotherapy (SABR) and the immune-checkpoint inhibitor atezolizumab was well tolerated, with the maximum tolerated dose established at 1200 mg.

Early efficacy signals were observed, with 17% of patients showing responses after two cycles of atezolizumab before starting SABR, and specific biomarkers indicating T cell activation were found to be predictive of treatment benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial. Monjazeb, AM., Daly, ME., Luxardi, G., et al.[2023]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]

Atezolizumab is an immunotherapy that effectively enhances T-cell activity against cancer by blocking the PD-L1/PD-1 interaction, which is crucial for tumor cells to evade the immune system.

It has been shown to be well tolerated in phase I trials with no dose-limiting toxicities and has received FDA approval for treating platinum-resistant metastatic non-small cell lung cancer and urothelial cancer, demonstrating significant improvements in patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A novel PD-L1 inhibitor in cancer therapy with a focus in bladder and non-small cell lung cancers. Krishnamurthy, A., Jimeno, A.[2019]

Atezolizumab, combined with carboplatin and etoposide, significantly improves overall survival and progression-free survival in patients with extensive-stage small cell lung cancer, based on data from the IMpower133 trial involving previously untreated patients.

The treatment regimen is generally well tolerated, with no new safety concerns identified, and it does not negatively impact patients' quality of life, making it a valuable first-line therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Extensive-Stage SCLC. Frampton, JE.[2021]

Stereotactic ablative radiotherapy (SABR) using Cyberknife demonstrated high effectiveness in treating stage I non-small-cell lung cancer, with 2-year local control, progression-free, and overall survival rates of 91.9%, 61.7%, and 84.8%, respectively, based on a study of 153 patients.

The treatment was generally safe, with only 8.1% of patients experiencing severe toxicities, including one case of grade 5 radiation pneumonitis, indicating that while SABR is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis. Hayashi, K., Suzuki, O., Shiomi, H., et al.[2022]

Atezolizumab (Tecentriq) is an FDA-approved treatment for unresectable or metastatic alveolar soft part sarcoma (ASPS), showing a 24% overall response rate in a clinical trial with 49 patients, and a durable response rate of 67% at 6 months and 42% at 12 months.

The treatment has a manageable safety profile, with common severe side effects including musculoskeletal pain (8%) and hypertension (6%), making it a viable option for patients with limited treatment alternatives for this high-risk disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab as the First Systemic Therapy Approved for Alveolar Soft Part Sarcoma. Bergsma, EJ., Elgawly, M., Mancuso, D., et al.[2023]

In a phase 2 study involving 45 patients with invasive bladder cancer, the combination of radiation therapy and atezolizumab resulted in a high pathologic complete response (pCR) rate of 84.4%, particularly in older patients and those with high PD-L1 expression.

The treatment was associated with acceptable toxicity, with 93.3% of patients experiencing adverse events, mostly mild to moderate, and only 13.3% experiencing grade 3 adverse events, indicating that this approach could be a viable bladder-preserving option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Bladder Preservation Therapy in Combination with Atezolizumab and Radiation Therapy (BPT-ART) for Invasive Bladder Cancer: Interim Analysis from a Multicenter, Open-label, Prospective Phase 2 Trial. Kimura, T., Ishikawa, H., Nagumo, Y., et al.[2023]

References

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

Atezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial. [2023]

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

Atezolizumab: First Global Approval. [2019]

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

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]

4. Spain pubmed.ncbi.nlm.nih.gov

Atezolizumab: A novel PD-L1 inhibitor in cancer therapy with a focus in bladder and non-small cell lung cancers. [2019]

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

Atezolizumab: A Review in Extensive-Stage SCLC. [2021]

6. Greece pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis. [2022]

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

Atezolizumab as the First Systemic Therapy Approved for Alveolar Soft Part Sarcoma. [2023]

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

Efficacy and Safety of Bladder Preservation Therapy in Combination with Atezolizumab and Radiation Therapy (BPT-ART) for Invasive Bladder Cancer: Interim Analysis from a Multicenter, Open-label, Prospective Phase 2 Trial. [2023]