Atezolizumab + Tiragolumab for Non-Small Cell Lung Cancer

Not currently recruiting at 16 trial locations

Overseen By Quality Management and Compliance

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alliance Foundation Trials, LLC.

Must not be taking: Immunosuppressants, Immunostimulants

Disqualifiers: Autoimmune disease, Cardiac disease, Infection, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a combination of two immunotherapy drugs, atezolizumab (Tecentriq) and tiragolumab, to treat non-small cell lung cancer (NSCLC) that cannot be removed by surgery. The researchers aim to determine if these drugs, administered before and after standard chemoradiotherapy, can better manage stage III NSCLC. Individuals diagnosed with stage III NSCLC who cannot undergo surgery might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in NSCLC treatment.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that certain medications, like systemic immunosuppressive drugs, should not be taken within 2 weeks before starting the study treatment. It's best to discuss your current medications with the study team to get specific guidance.

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

Previous studies have shown that atezolizumab can cause side effects. About 27.7% of patients experienced immune-related issues, with serious effects in 9.9% and very serious ones in 2.1%. This indicates that a small number of people had strong reactions to the drug.

Research shows that when combined with tiragolumab, atezolizumab is generally well-tolerated. No new safety issues emerged when these drugs were used together, suggesting that their combination does not add extra risks compared to using atezolizumab alone.

Overall, while possible side effects exist, both treatments have been tested and are considered safe enough for continued study in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about atezolizumab and tiragolumab for non-small cell lung cancer because they offer a fresh approach to treatment. Unlike traditional chemotherapy, which attacks cancer cells broadly, atezolizumab and tiragolumab are immunotherapies that work by boosting the body's own immune response to specifically target cancer cells. Atezolizumab blocks the PD-L1 protein to prevent cancer cells from hiding, while tiragolumab targets the TIGIT pathway to further enhance immune activation. This dual action not only promises a more precise attack on cancer but also aims to reduce the side effects typically associated with conventional treatments.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research has shown that atezolizumab, which participants in this trial may receive, effectively treats non-small cell lung cancer (NSCLC). Studies found that patients with advanced NSCLC lived longer with atezolizumab than with chemotherapy, showing a 41% lower risk of death. Atezolizumab also aids long-term survival, particularly when used post-surgery.

In this trial, some participants will receive a combination of tiragolumab and atezolizumab. Previous studies have shown mixed results with this combination. Some studies did not find significant survival improvements for patients with high levels of PD-L1, a protein that helps some cancer cells evade the immune system. However, other research has reported promising survival outcomes with this combination. ^{1 4 6 7 8}

Who Is on the Research Team?

Helen Ross, MD

Principal Investigator

Rush University

Evanthia Galanis, MD

Principal Investigator

Alliance Foundation Trials, LLC.

Are You a Good Fit for This Trial?

This trial is for adults with a new diagnosis of stage IIIA/B/C non-small cell lung cancer (NSCLC) who haven't had systemic therapy or radiation for their lung cancer. They should have normal organ function, no active autoimmune diseases, and be able to provide a tumor tissue sample. Patients unfit for surgery but fit for chemoradiotherapy can join.

Inclusion Criteria

Negative HIV test at screening

Non-pregnant and non-nursing

My cancer is at stage III A/B/C and was diagnosed or evaluated in the last 6 weeks.

Exclusion Criteria

I haven't taken immune-boosting drugs recently.

I can understand and follow the study's procedures.

I have been hospitalized for a severe lung condition recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Immunotherapy

Participants receive induction immunotherapy with atezolizumab with or without tiragolumab on Day 1 of each cycle

6 weeks

1 visit per cycle (in-person)

Concurrent Chemoradiotherapy

Participants receive concurrent chemoradiotherapy with atezolizumab with or without tiragolumab

6 weeks

Weekly visits (in-person)

Adjuvant Immunotherapy

Participants receive adjuvant atezolizumab with or without tiragolumab on Day 1 of each cycle

6 months

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Tiragolumab

Trial Overview The study tests the effectiveness of Atezolizumab immunotherapy alone or combined with Tiragolumab in addition to standard chemoradiotherapy. It's designed to see if adding Tiragolumab improves outcomes in unresectable stage III NSCLC patients.

How Is the Trial Designed?

Group I: Arm C: Atezolizumab and Tiragolumab Experimental Treatment 2 Interventions

An additional pilot cohort of 20 patients will be accrued at selected sites towards the end of the overall accrual period and after initial safety evaluations of the addition of tiragolumab to atezolizumab before and after chemoradiotherapy. Participants enrolled to Arm C will receive induction immunotherapy with atezolizumab plus tiragolumab on Day 1 of each cycle, concurrent atezolizumab plus tiragolumab with chemoradiotherapy, and adjuvant atezolizumab plus tiragolumab on Day 1 of each 21 cycle.

Group II: Arm B: Atezolizumab and Tiragolumab Experimental Treatment 2 Interventions

79 participants will be randomized 1:1 to Arm B. Participants in Arm B will receive induction immunotherapy with atezolizumab plus tiragolumab on Day 1 of each cycle, concurrent chemoradiotherapy, and adjuvant atezolizumab plus tiragolumab on Day 1 of each cycle.

Group III: Arm A: Atezolizumab Experimental Treatment 1 Intervention

79 participants will be randomized 1:1 to Arm A. Participants in Arm A will receive induction immunotherapy with atezolizumab on Day 1 of each cycle, concurrent chemoradiotherapy, and adjuvant atezolizumab Day 1 of each 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?

Alliance Foundation Trials, LLC.

Lead Sponsor

Trials

25

Recruited

27,200+

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

Atezolizumab significantly improves overall survival in patients with metastatic non-small cell lung cancer (mNSCLC), with median survival times of 13.8 months in the atezolizumab group compared to 9.6 months in the docetaxel group in the OAK trial.

The treatment has an acceptable safety profile, with common side effects including fatigue and decreased appetite, and serious immune-related adverse events occurring in a small percentage of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. Weinstock, C., Khozin, S., Suzman, D., 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 significantly improved overall survival in patients with previously treated non-small-cell lung cancer compared to docetaxel, with median survival times of 13.8 months versus 9.6 months, respectively.

The safety profile of atezolizumab was favorable, with only 15% of patients experiencing grade 3 or 4 adverse events, compared to 43% in the docetaxel group, indicating it may be a safer treatment option.

NCBI (Pubmed)

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. Rittmeyer, A., Barlesi, F., Waterkamp, D., et al.[2022]

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]

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]

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]

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]

Anti-PD-1 and anti-PD-L1 antibodies, such as pembrolizumab, nivolumab, atezolizumab, and durvalumab, are effective first-line treatments for advanced non-small-cell lung cancer (NSCLC) without targetable genetic alterations, based on recent clinical trials.

Factors like patient characteristics, tumor histology, and biomarkers (e.g., PD-L1 expression) play a crucial role in determining the most suitable treatment approach for individual patients with NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How to make the best use of immunotherapy as first-line treatment of advanced/metastatic non-small-cell lung cancer. Peters, S., Reck, M., Smit, EF., et al.[2020]

Citations

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updated long-term efficacy of atezolizumab in a diverse ... In patients with previously treated advanced or metastatic non-small cell lung cancer (NSCLC), atezolizumab therapy improves survival with manageable safety.

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

Effectiveness & Safety of TECENTRIQ® (atezolizumab) for ... TECENTRIQ helped people with a type of metastatic non-small cell lung cancer (NSCLC) live longer. TECENTRIQ was studied in 4 clinical trials with over 2000 ...

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Five-Year Survival Outcomes With Atezolizumab After ... IMpower010 is the first study to report survival outcomes with a ≥5-year follow-up and continued to show benefit with atezolizumab versus BSC after adjuvant ...

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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 ...

5. tecentriq.com tecentriq.com/nsclc-after-surgery/results/how-tecentriq-may-help.html

TECENTRIQ may prevent your PD-L1+ non-small cell lung ... At that first analysis, the risk of people dying was 23% lower with TECENTRIQ than with best supportive care.

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Outcomes of Combined Atezolizumab Plus Chemotherapy in ... Immune-related adverse events were observed in 27.7% of patients, with grade 3 or higher in 9.9% of patients, and grade 5 in 2.1% of patients.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e20007

Efficacy and safety analysis of adjuvant atezolizumab in ... We assessed 1-year and 2-year DFS rates and OS rates. Safety of immunotherapy was evaluated in all patients. Results: From June 21, 2022 to ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03285763

NCT03285763 | A Study of Atezolizumab (Tecentriq) to ... This is a Phase III/IV, single-arm, multicenter study of the long-term safety and efficacy of atezolizumab treatment in participants with Stage IIIb or ...