Tiragolumab + Atezolizumab for Oral Cancer

Overseen By Michael Wotman, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

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

Disqualifiers: Autoimmune disease, Cardiovascular disease, others

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: Unknown

29 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether two drugs, tiragolumab and atezolizumab (Tecentriq), can help control oral cancer known as OCSCC. Researchers aim to determine if administering these drugs before and after standard treatments, such as surgery and radiation, is effective for individuals with PD-L1 CPS positive cancer (a specific protein marker on cancer cells). The trial seeks participants with newly diagnosed or recurrent oral cavity cancer that has not undergone head and neck radiation and is considered removable with surgery. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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, it does mention that patients on certain treatments, like systemic immunosuppressive medications, may need to stop or adjust their use before starting the trial. It's best to discuss your specific medications with the trial team.

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

Research has shown that the combination of tiragolumab and atezolizumab is generally safe. One study found that patients using these treatments did not experience severe side effects. Although the combination was less effective in some cases, its safety remained stable. Another study is examining their use in oral cancer to determine if the side effects are manageable. Since this trial is in Phase 2, the treatment has demonstrated some safety in earlier studies. These findings suggest the treatment might be safe for participants, but monitoring for side effects remains crucial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Tiragolumab and Atezolizumab for oral cancer because these treatments offer a novel approach by targeting the immune system differently from standard therapies. Most current treatments involve surgery, radiation, and chemotherapy, which directly attack cancer cells. However, Atezolizumab is an immune checkpoint inhibitor that blocks the PD-L1 protein, helping the immune system recognize and destroy cancer cells. Tiragolumab adds an extra layer of action by targeting another checkpoint, TIGIT, potentially enhancing the immune response even further. This dual targeting may lead to more effective and longer-lasting responses compared to existing treatments.

What evidence suggests that this trial's treatments could be effective for oral cancer?

Research has shown that using tiragolumab with atezolizumab, which participants in this trial may receive, may help treat oral cancer. Studies have found that adding tiragolumab to atezolizumab can boost the body's immune response against cancer cells. In one study, this combination was compared to using atezolizumab alone and improved patient outcomes for certain cancer types. Tiragolumab blocks a protein that allows cancer cells to hide from the immune system, while atezolizumab helps the immune system find and attack these cells. Early results suggest this combination could be effective, especially for patients whose tumors have a specific marker called PD-L1. ^{1 4 5 6 7}

Who Is on the Research Team?

Michael Wotman

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults with newly diagnosed, PD-L1 CPS positive, resectable Stage 3-4 Oral Cavity Squamous Cell Carcinoma (OCSCC) who are in good physical condition (ECOG 0-1), have measurable disease per RECIST v1.1, and can comply with the study protocol. Excluded are those with prior significant treatments or conditions that could interfere with the trial, such as autoimmune diseases, recent infections including COVID-19, or allergies to trial medications.

Inclusion Criteria

Negative HIV test at screening

My blood and organs are functioning well.

Negative hepatitis C virus (HCV) antibody test at screening

Exclusion Criteria

History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins

I have had cancer within the last 5 years.

Treatment with investigational therapy within 42 days prior to initiation of study treatment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive two cycles of neoadjuvant atezolizumab and tiragolumab

6-8 weeks

Surgery and Chemoradiation

Participants undergo standard of care surgery followed by chemoradiation

8-12 weeks

Adjuvant Treatment

Participants receive adjuvant atezolizumab and tiragolumab

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12-24 months

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Carboplatin
• Cisplatin
• Standard of Care
• Tiragolumab

Trial Overview The effectiveness of Tiragolumab plus Atezolizumab before and after surgery and chemoradiation is being tested against OCSCC. The goal is to see if these drugs can better control cancer when added to standard treatment which may include radiation therapy alongside chemotherapy agents like Cisplatin or Carboplatin.

How Is the Trial Designed?

Group I: Neoadjuvant and Adjuvant Experimental Treatment 6 Interventions

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

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

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]

Pembrolizumab, an anti-PD-1 antibody used for treating various cancers, can cause immune-related adverse events (IRAEs) affecting multiple body systems, including rare oral mucosal issues like glossitis.

In a case study of a 71-year-old male with lung cancer, treatment with oral prednisone effectively improved tongue ulcerations caused by pembrolizumab, highlighting the need for awareness of such rare side effects and their management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab-Induced Immune-Mediated Glossitis. Alias, A., Hall, JA., Kulkarni, P., et al.[2022]

Atezolizumab combined with chemotherapy showed promising efficacy in treating advanced, treatment-naïve non-small-cell lung cancer (NSCLC), with overall response rates of 36% to 68% across different chemotherapy regimens in a study of 76 patients.

The treatment was generally well tolerated, although common severe side effects included neutropenia and anemia, indicating a manageable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival follow-up of atezolizumab in combination with platinum-based doublet chemotherapy in patients with advanced non-small-cell lung cancer. Liu, SV., Camidge, DR., Gettinger, SN., et al.[2022]

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]

A 78-year-old woman developed Grade 3 ulcerative oral mucositis 13 months after starting treatment with the PD-1 inhibitor pembrolizumab for lung adenocarcinoma, highlighting a potential severe side effect of this therapy.

The patient was successfully treated with prednisone, indicating that while severe mucositis can occur, it can be managed effectively, and physicians should be vigilant about this risk when prescribing PD-1 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe Oral Mucositis: A Rare Adverse Event of Pembrolizumab. Lederhandler, MH., Ho, A., Brinster, N., et al.[2018]

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]

In a trial involving 20 patients with recurrent/metastatic oral squamous cell carcinoma, the combination of camrelizumab with docetaxel and cisplatin showed a median overall survival of 14.4 months and an overall response rate of 40%, indicating promising efficacy.

The treatment was generally well tolerated, with 45% of patients experiencing grade ≥ 3 treatment-related adverse events, the most common being anemia and stomatitis, but no treatment-related deaths occurred.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of camrelizumab with docetaxel and cisplatin for the first line treatment in recurrent/metastatic oral squamous cell carcinoma. Ju, H., Wei, D., Wu, Y., et al.[2023]

Atezolizumab, a monoclonal antibody targeting PD-L1, showed a 23% response rate and a median overall survival of 15.9 months in 119 patients with metastatic urothelial cancer who were unfit for cisplatin, indicating its efficacy as a front-line treatment.

In patients whose tumors progressed after first-line chemotherapy, atezolizumab had a 15% response rate and a median overall survival of 7.9 months, with better outcomes (26% response rate) in those with high PD-L1 expression, demonstrating its potential effectiveness based on biomarker status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Atezolizumab (Tecentriq®): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. Bernard-Tessier, A., Bonnet, C., Lavaud, P., et al.[2019]

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]

This report describes the first known case of oral mucous membrane pemphigoid and lichenoid reaction triggered by the anti-PD-1 monoclonal antibodies toripalimab and pembrolizumab, highlighting potential mucocutaneous adverse effects associated with these treatments.

While discontinuing these medications led to clinical resolution of the adverse events, existing studies suggest that such dermatologic reactions may correlate with better cancer treatment outcomes, indicating a need for further research to balance efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Coexistence of oral mucous membrane pemphigoid and lichenoid drug reaction: a case of toripalimab-triggered and pembrolizumab-aggravated oral adverse events. Duan, S., Zhang, X., Wang, F., et al.[2021]

Citations

1. withpower.com withpower.com/trial/phase-2-carcinoma-5-2023-8c307

Tiragolumab + Atezolizumab for Oral Cancer This Phase 2 medical study run by M.D. Anderson Cancer Center is evaluating whether Atezolizumab and Tiragolumab will have tolerable side effects & efficacy ...

2. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/Head_and_Neck_Cancer/a-study-of-atezolizumab-plus-tiragolumab-and-atezolizum-41714.html

A clinical trial to evaluate atezolizumab plus tiragoluma... This study aims to compare the efficacy of atezolizumab plus tiragolumab and atezolizumab plus placebo each against a historical control arm in people with ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05681039

Phase 2 Trial of Neoadjuvant and Adjuvant Tiragolumab ... To investigate changes in the tumor microenvionment before and after two cycles of atezolizumab and tiragolumab as measured by multispectral immunofluorescence ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04665843

NCT04665843 | A Study of Atezolizumab Plus Tiragolumab ... The primary objective of this study is to evaluate the efficacy of atezolizumab plus tiragolumab and atezolizumab plus placebo as first-line (1L) treatment ...

5. gene.com gene.com/media/press-releases/14937/2021-12-10/new-data-from-the-phase-ii-cityscape-tri

Genentech: Press Releases | Friday, Dec 10, 2021 CITYSCAPE is a global Phase II, randomized and blinded study evaluating tiragolumab plus Tecentriq® (atezolizumab) compared with Tecentriq alone ...

6. gene.com gene.com/media/press-releases/15029/2024-07-03/genentech-provides-update-on-phase-iiiii

Genentech: Press Releases | Wednesday, Jul 3, 2024 The combination of tiragolumab plus Tecentriq and chemotherapy showed reduced efficacy in both PFS and OS compared to the comparator arm in the intent-to-treat ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04619797

NCT04619797 | A Study of Tiragolumab in Combination ... The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of tiragolumab in combination with atezolizumab plus pemetrexed and ...