Atezolizumab + Tiragolumab for Head and Neck Cancer

(SKYSCRAPER-09 Trial)

Recruiting at 86 trial locations

Overseen By Reference Study ID Number: BO42533 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hoffmann-La Roche

Must not be taking: Immunostimulants, Immunosuppressants

Disqualifiers: CNS metastases, Autoimmune disease, others

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: 1

Duration: 21-day cycles

123 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective of this study is to evaluate the efficacy of atezolizumab plus tiragolumab and atezolizumab plus placebo as first-line (1L) treatment in recurrent/metastatic PD-L1-positive squamous cell carcinoma of the head and neck (SCCHN) on the basis of confirmed objective response rate. In addition, safety, pharmacokinetics, immunogenicity of atezolizumab and tiragolumab will be evaluated.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but it excludes those on systemic immunostimulatory or immunosuppressive medications. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Atezolizumab and Tiragolumab for head and neck cancer?

Research shows that Atezolizumab, which blocks a protein called PD-L1, has been effective in treating various cancers, including head and neck cancer. Additionally, combining Tiragolumab with Atezolizumab has improved outcomes in non-small cell lung cancer, suggesting potential benefits for other cancers as well. ^{1 2 3 4 5}

Is the combination of Atezolizumab and Tiragolumab safe for humans?

Atezolizumab has a favorable safety profile, with most side effects being mild, such as skin rashes. However, there is a rare report of a severe skin reaction called Stevens-Johnson syndrome. Tiragolumab, when combined with Atezolizumab, has shown promising results in trials for various cancers, but specific safety data for this combination in head and neck cancer is not detailed. ^{2 3 6 7 8}

How is the drug combination of atezolizumab and tiragolumab unique for head and neck cancer?

The combination of atezolizumab and tiragolumab is unique because it targets two immune checkpoints, PD-L1 and TIGIT, which may enhance the immune system's ability to fight cancer cells. This dual approach is being explored for its potential to improve outcomes in cancers like head and neck cancer, where traditional immune checkpoint inhibitors alone have limited effectiveness. ^{2 3 6 8 9}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with recurrent or metastatic PD-L1 positive squamous cell carcinoma of the head and neck. Participants must have measurable disease, an ECOG status of 0 or 1, a life expectancy of at least 12 weeks, and no prior systemic therapy for their condition. They cannot join if they are pregnant, breastfeeding, have certain lung conditions or other cancers within the last five years, untreated brain metastases, rapid disease progression or recent immunotherapy.

Inclusion Criteria

I am fully active or can carry out light work.

Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

You are expected to live for at least 12 more weeks.

Exclusion Criteria

I have not had any cancer other than SCCHN in the last 5 years.

I am currently taking or have recently taken drugs that affect my immune system.

I have lasting side effects from past treatments or surgeries.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atezolizumab plus tiragolumab or atezolizumab plus placebo every three weeks on Day 1 of each 21-day cycle

21-day cycles

1 visit every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Atezolizumab
• Placebo
• Tiragolumab

Trial Overview The study tests how well Atezolizumab combined with Tiragolumab works compared to Atezolizumab with a placebo in treating this type of cancer as a first-line treatment. It measures the rate at which tumors respond to these treatments and also looks into safety and how the body processes these drugs.

Participant Groups

Group I: Atezolizumab + Tiragolumab Experimental Treatment 2 Interventions

Participants will receive atezolizumab followed by tiragolumab every three weeks (Q3W) on Day 1 of each 21-day cycle.

Group II: Atezolizumab + Placebo Placebo Group 2 Interventions

Participants will receive atezolizumab followed by placebo Q3W on Day 1 of each 21-day cycle.

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?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

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]

This phase I clinical trial is investigating the safety and efficacy of combining the anti-TIGIT monoclonal antibody tiragolumab with the PD-L1 inhibitor atezolizumab and Stereotactic Body Radiation Therapy (SBRT) in patients with metastatic non-small cell lung cancer and other cancers previously treated with immune checkpoint inhibitors.

The primary goal of the trial is to assess the safety of this combination treatment and to evaluate its effectiveness in improving 6-month progression-free survival (PFS), with the study including multiple cancer types and a focus on immune biomarker assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of the combination of atezolizumab, tiragolumab, and stereotactic body radiation therapy in patients with metastatic multiorgan cancer. Roussot, N., Fumet, JD., Limagne, E., et al.[2023]

Tiragolumab, a TIGIT inhibitor, shows promise in treating solid cancers, particularly non-small cell lung cancer, based on results from phase I and II trials.

The combination of tiragolumab with the PD-L1 inhibitor atezolizumab has demonstrated statistically significant efficacy in multiple solid tumors, suggesting a potential new treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiragolumab Impresses in Multiple Trials. [2021]

In a study involving 133 patients with locally advanced squamous cell carcinoma of the head and neck, pembrolizumab combined with radiotherapy did not show a significant improvement in locoregional control or survival compared to the standard treatment of cetuximab with radiotherapy.

However, patients receiving pembrolizumab experienced significantly lower toxicity, with only 74% reporting severe adverse events compared to 92% in the cetuximab group, suggesting it may be a safer option for patients unfit for high-dose cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial. Tao, Y., Biau, J., Sun, XS., et al.[2023]

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, an anti-PD-L1 antibody used for treating advanced cancers like metastatic non-small cell lung cancer, has a low incidence of cutaneous side effects, with only 20% of patients experiencing mild rashes that did not require treatment.

There have been no reported cases of severe skin reactions such as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) associated with atezolizumab, suggesting a favorable safety profile for dermatological side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab-Induced Stevens-Johnson Syndrome in a Patient with Non-Small Cell Lung Carcinoma. Chirasuthat, P., Chayavichitsilp, P.[2020]

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]

In the CITYSCAPE trial involving 275 patients with chemotherapy-naive, PD-L1-positive non-small-cell lung cancer, the combination of tiragolumab and atezolizumab resulted in a significantly higher objective response rate (31.3% vs. 16.2%) and improved median progression-free survival (5.4 months vs. 3.6 months) compared to placebo plus atezolizumab.

The safety profile of tiragolumab plus atezolizumab was generally similar to that of atezolizumab alone, with serious treatment-related adverse events occurring in 21% of patients in the combination group, indicating that this combination therapy is well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): primary and follow-up analyses of a randomised, double-blind, phase 2 study. Cho, BC., Abreu, DR., Hussein, M., et al.[2022]

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. England pubmed.ncbi.nlm.nih.gov

A phase I study of the combination of atezolizumab, tiragolumab, and stereotactic body radiation therapy in patients with metastatic multiorgan cancer. [2023]

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

Tiragolumab Impresses in Multiple Trials. [2021]

4. India pubmed.ncbi.nlm.nih.gov

Nimotuzumab plus chemotherapy with docetaxel, cisplatin, 5-fluorouracil for locally advanced head and neck squamous cell carcinoma: A clinical study. [2022]

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

Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial. [2023]

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

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

7. Switzerland pubmed.ncbi.nlm.nih.gov

Atezolizumab-Induced Stevens-Johnson Syndrome in a Patient with Non-Small Cell Lung Carcinoma. [2020]

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

Atezolizumab: First Global Approval. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): primary and follow-up analyses of a randomised, double-blind, phase 2 study. [2022]