Radiotherapy + Atezolizumab for Squamous Cell Carcinoma

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining radiotherapy with the drug atezolizumab (Tecentriq) for treating cutaneous squamous cell carcinoma. This type of skin cancer has either spread to nearby areas or cannot be fully removed by surgery. Radiotherapy precisely targets tumors, while atezolizumab boosts the immune system to fight cancer cells. Suitable participants have this specific type of skin cancer that has spread locally or to a few distant spots. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this combination therapy.

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.

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

Research shows that combining atezolizumab with a type of radiation therapy called SBRT is generally safe and well-tolerated. In earlier studies, patients who received this combination treatment experienced manageable side effects. Most side effects were mild, such as tiredness and skin irritation, and serious side effects were rare.

Atezolizumab, an immunotherapy drug, helps the body's immune system fight cancer. The FDA has already approved it for treating other types of cancer, indicating a certain level of safety. The radiation therapy used in this trial, SBRT, is known for its precision. It targets tumors closely, helping to protect healthy tissue.

Overall, earlier research suggests that this combination of treatments is promising and seems to be a safe option for patients, although more studies are needed to confirm these findings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Radiotherapy combined with atezolizumab is unique because it pairs a precise radiation technique with an innovative immunotherapy approach. Stereotactic Body Radiation Therapy (SBRT) delivers high doses of radiation directly to the tumor in just a few sessions, which is quicker and often more effective than traditional radiation methods. Atezolizumab, an immune checkpoint inhibitor, helps the body's immune system better recognize and attack cancer cells. This combination could potentially enhance the effectiveness of treatment for squamous cell carcinoma by both directly targeting the cancer and boosting the body's natural defenses. Researchers are excited because this dual approach might offer improved outcomes compared to existing treatments, which typically involve surgery, conventional radiation, and chemotherapy.

What evidence suggests that radiotherapy combined with atezolizumab could be effective for squamous cell carcinoma?

This trial will evaluate the combination of Stereotactic Body Radiation Therapy (SBRT) and atezolizumab for squamous cell carcinoma. Studies have shown that atezolizumab, a type of immunotherapy, can help patients live longer without tumor growth or spread in certain cancers. For instance, in lung cancer patients, it reduced the risk of death by 41% compared to chemotherapy. Although results for squamous cell carcinoma are not as strong, there is hope that it might help by boosting the immune system to fight cancer cells. Meanwhile, SBRT is known for its precision in targeting tumors and can achieve high success rates in tumor control, with two-year survival rates over 70% in some cases. This trial will test whether combining SBRT with atezolizumab could potentially offer better results than using either treatment alone. ^{6 7 8 9 10}

Who Is on the Research Team?

Arya Amini

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

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

I am willing and able to follow the study's treatment plan and attend all visits.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 (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]

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 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, 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]

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]

Citations

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IMpower110 Clinical Trial Results - TECENTRIQ-HCP.com 41% reduction in the risk of death vs chemotherapy · Median PFS was 8.1 months with TECENTRIQ (95% CI, 6.8, 11.0) vs 5.0 months with platinum-based chemotherapy ...

3. tecentriq.com tecentriq.com/metastatic-nsclc/results/how-tecentriq-may-help.html

Effectiveness & Safety of TECENTRIQ® (atezolizumab) for ... Median progression-free survival: The amount of time that half the people lived without their tumors growing or spreading was 7 months for those not taking ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9716834/

updated long-term efficacy of atezolizumab in a diverse ... Patients received atezolizumab intravenously (1200 mg) every 3 weeks. At data cut-off for final analysis, the median follow-up was 36.1 (range 0.0–42.3) months.

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Atezolizumab in High-Risk Locally Advanced Squamous ... There was no difference in overall survival between atezolizumab and placebo (24-month overall survival, 82.0% vs 79.2%, respectively). No new ...

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Atezolizumab and stereotactic body radiotherapy in patients ... In this phase II trial, we investigated the toxicity, systemic responses and circulating tumour DNA responses in patients (n = 21) with advanced ...

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Atezolizumab plus stereotactic ablative radiotherapy for ... The authors report the results of a phase I study testing the addition of atezolizumab (anti-PD-L1) to SABR in high risk, medically inoperable, early-stage, ...

8. withpower.com withpower.com/trial/phase-1-carcinoma-10-2021-3edc8

Radiotherapy + Atezolizumab for Squamous Cell Carcinoma This phase I trial tests the safety and side effects radiotherapy in combination with atezolizumab in treating patients with cutaneous squamous cell cancer ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT06416436

NCT06416436 | Dose-escalation Study of Ultra-high ... To assess the progression-free survival of participants receiving ultra-high dose SBRT with concurrent and adjuvant atezolizumab in participants with cancer who ...

10. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.9011

Atezolizumab plus stereotactic ablative therapy for ... Atezolizumab plus SABR is feasible, safe and shows an efficacy signal in medically inoperable early stage NSCLC.