Atezolizumab + Tiragolumab for Non-Small Cell Lung Cancer

Recruiting at 11 trial locations

Overseen By Quality Management and Compliance

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Alliance Foundation Trials, LLC.

Must not be taking: Immunosuppressants, Immunostimulants

Disqualifiers: Autoimmune disease, Cardiac disease, Infection, others

Stay on Your Current Meds

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This is a phase II trial of neoadjuvant and adjuvant atezolizumab with or without tiragolumab in conjunction with chemoradiotherapy for unresectable stage III NSCLC.

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.

What data supports the effectiveness of the drug combination Atezolizumab and Tiragolumab for non-small cell lung cancer?

Research shows that the combination of tiragolumab and atezolizumab may be effective against non-small cell lung cancer, with significant results in trials. Atezolizumab, when used alone, has also shown effectiveness in treating other cancers like bladder cancer, suggesting its potential in combination therapies. ^{1 2 3 4 5}

Is the combination of Atezolizumab and Tiragolumab safe for humans?

Atezolizumab has been shown to have an acceptable safety profile in clinical trials for non-small cell lung cancer and bladder cancer, with common side effects including fatigue, decreased appetite, and nausea. Tiragolumab, when combined with Atezolizumab, has been studied for safety in non-small cell lung cancer, but specific safety data for this combination is limited. ^{2 3 5 6 7}

What makes the drug Atezolizumab + Tiragolumab unique for non-small cell lung cancer?

The combination of Atezolizumab and Tiragolumab is unique because it targets two different immune checkpoints, PD-L1 and TIGIT, which may enhance the immune system's ability to fight non-small cell lung cancer more effectively than targeting PD-L1 alone. ^{1 2 3 5 8}

Research Team

Helen Ross, MD

Principal Investigator

Rush University

Evanthia Galanis, MD

Principal Investigator

Alliance Foundation Trials, LLC.

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Atezolizumab (Checkpoint Inhibitor)
• Tiragolumab (Checkpoint Inhibitor)

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.

Participant Groups

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.

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

Findings from Research

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 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]

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]

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 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]

References

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

Tiragolumab Impresses in Multiple Trials. [2021]

2. 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]

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

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

4. England 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. [2020]

5. England 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. [2022]

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

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. [2022]

7. England 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. [2022]

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

Atezolizumab: First Global Approval. [2019]