Tiragolumab + Atezolizumab for Non-Small Cell Lung Cancer

Not currently recruiting at 72 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Genentech, Inc.

Must not be taking: Bisphosphonates, Denosumab

Disqualifiers: EGFR mutation, ALK translocation, CNS metastases, 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: 3

Duration: 11 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of medicines, tiragolumab and atezolizumab (also known as Tecentriq, an immunotherapy drug), to determine if they can more effectively treat certain types of advanced non-small cell lung cancer (NSCLC). The goal is to assess whether this combination works better and is safer than using atezolizumab alone with a placebo. People with NSCLC that hasn't been treated with chemotherapy and is not linked to specific genetic mutations (EGFR or ALK) might be suitable candidates. Participants will receive either both drugs or a placebo with atezolizumab to compare outcomes. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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 has been tested for safety in several studies. These studies found no major safety issues with the combination, but it did not significantly improve survival compared to other treatments. This indicates that while the combination is generally safe, it might not be more effective than current options.

Most patients who received tiragolumab and atezolizumab tolerated the treatment well without unexpected side effects. However, like any treatment, some individuals might experience common side effects such as tiredness, nausea, or infusion-related reactions. Participants should discuss any concerns with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of tiragolumab and atezolizumab for treating non-small cell lung cancer because it offers a novel approach to boosting the immune system's ability to fight cancer. Unlike most treatments that focus solely on targeting specific cancer cells, tiragolumab is a TIGIT inhibitor, which helps unleash the full potential of immune cells by blocking a pathway that tumors use to evade them. This is combined with atezolizumab, a PD-L1 inhibitor, which further enhances immune response by preventing cancer cells from hiding from the immune system. This dual-action mechanism is expected to offer a more comprehensive attack on cancer cells, potentially leading to improved outcomes for patients.

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

This trial will compare the combination of Tiragolumab and Atezolizumab with Atezolizumab alone for treating non-small cell lung cancer (NSCLC). Research has shown that using Tiragolumab with Atezolizumab does not outperform Atezolizumab alone for NSCLC treatment. In earlier studies, this combination neither extended patients' lives nor prevented cancer progression, particularly in those with high levels of the protein PD-L1, which can influence cancer growth. Some studies even found it less effective than other treatments. These results suggest that while this combination might seem promising, it has not yet proven superior to current NSCLC treatments. ^{2 4 5 6 7}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-small cell lung cancer (NSCLC) that hasn't been treated with chemotherapy. Participants must have tumors expressing PD-L1, a life expectancy of at least 12 weeks, and good organ function. They should not be pregnant or breastfeeding, agree to use contraception, and have no history of certain diseases like autoimmune disorders or severe allergies to specific antibodies.

Inclusion Criteria

My lung cancer is advanced, cannot be surgically removed, and has been confirmed by lab tests.

My blood and organs are functioning well.

I agree to either not have sex or use birth control, and not donate sperm.

Exclusion Criteria

I have a serious heart condition.

I have not had a severe infection in the last 4 weeks.

Pregnant and lactating women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atezolizumab and either tiragolumab or placebo by IV infusion every 3 weeks

11 months

Visits every 3 weeks for IV infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 years

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Tiragolumab

Trial Overview

The study tests the combination of two drugs: Tiragolumab and Atezolizumab versus a placebo plus Atezolizumab in patients who haven't had chemo before. It aims to see if adding Tiragolumab improves outcomes in NSCLC patients selected based on PD-L1 expression.

How Is the Trial Designed?

Group I: Tiragolumab + Atezolizumab Experimental Treatment 2 Interventions

Participants will receive atezolizumab at a fixed dose of 1200 mg administered by intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle and tiragolumab at a dose of 600 mg administered by IV infusion Q3W on Day 1 of each 21-day cycle.

Group II: Placebo + Atezolizumab Placebo Group 2 Interventions

Participants will receive atezolizumab at a fixed dose of 1200 mg administered by IV infusion Q3W on Day 1 of each 21-day cycle and placebo administered by IV infusion 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?

Genentech, Inc.

Lead 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 phase III SKYSCRAPER-02 study involving 490 patients with untreated extensive-stage small-cell lung cancer, the addition of tiragolumab to atezolizumab and chemotherapy did not significantly improve progression-free survival (PFS) or overall survival (OS).

The combination treatment was well tolerated, with similar rates of immune-mediated adverse events between the tiragolumab and control groups, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SKYSCRAPER-02: Tiragolumab in Combination With Atezolizumab Plus Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer. Rudin, CM., Liu, SV., Soo, RA., et al.[2023]

Atezolizumab therapy significantly improves overall survival (median OS of 11.2 months) in patients with previously treated advanced non-small cell lung cancer (NSCLC), demonstrating its efficacy in a diverse patient population.

The treatment has a manageable safety profile, with serious adverse events occurring in only 8.0% of patients and no new safety signals identified, indicating it is a viable option for patients often excluded from clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final results from TAIL: updated long-term efficacy of atezolizumab in a diverse population of patients with previously treated advanced non-small cell lung cancer. Ardizzoni, A., Azevedo, S., Rubio-Viqueira, B., et al.[2022]

Atezolizumab, a PD-L1 blocking antibody, shows higher rates of objective response, progression-free survival, and overall survival when used as a first-line therapy in chemotherapy-naïve patients with metastatic non-small cell lung cancer (NSCLC), compared to its use in later treatment lines.

The review included 15 ongoing studies, with 5 reporting results, indicating that atezolizumab is being explored in various treatment combinations and settings, suggesting its potential as a versatile first-line treatment option for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for the First-Line Treatment of Non-small Cell Lung Cancer (NSCLC): Current Status and Future Prospects. Ryu, R., Ward, KE.[2023]

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 the first approved anti-PD-L1 inhibitor for treating squamous cell lung cancer (SqCLC) in patients who have experienced disease progression after initial therapies, highlighting its role in advanced stages of non-small cell lung cancer (NSCLC).

Current research is exploring atezolizumab's effectiveness in various treatment settings for SqCLC, indicating its potential for broader applications in future clinical scenarios, although specific target agents for this cancer subtype remain limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti PD-L1 antibody: is there a histologic-oriented efficacy? Focus on atezolizumab in squamous cell non-small cell lung cancer. Gemelli, M., Bidoli, P., Colonese, F., 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]

Atezolizumab significantly improves overall survival (OS) and progression-free survival (PFS) in patients with advanced non-small cell lung cancer (NSCLC) compared to chemotherapy, based on a meta-analysis of 7 randomized clinical trials involving 4,859 patients.

The effectiveness of atezolizumab varies based on clinical and molecular features, with better outcomes observed in younger patients, those with wild-type EGFR, and active or previous smokers, highlighting the importance of personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Atezolizumab for Advanced Non-Small Cell Lung Cancer Based on Clinical and Molecular Features: A Meta-Analysis. Liu, W., Huo, G., Chen, P.[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]

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 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]

Citations

1.

onclive.com

onclive.com/view/tiragolumab-plus-atezolizumab-fails-to-meet-survival-end-points-in-previously-untreated-pd-l1-high-nsclc

Tiragolumab Plus Atezolizumab Fails to Meet Survival End ...

First-line tiragolumab plus atezolizumab did not improve PFS and OS vs atezolizumab alone in PD-L1–high, unresectable or metastatic NSCLC.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06267001

NCT06267001 | A Study of Tiragolumab Plus Atezolizumab ...

The purpose of this study was to evaluate the efficacy and safety of tiragolumab plus atezolizumab compared with placebo plus atezolizumab administered to ...

3.

lungcancerstoday.com

lungcancerstoday.com/post/officials-skyscraper-06-study-of-tiragolumab-plus-atezolizumab-in-nonsquamous-nsclc-intended-to-halt

SKYSCRAPER-06 Study of Tiragolumab Plus ...

“The combination of tiragolumab plus Tecentriq and chemotherapy showed reduced efficacy in both PFS and OS compared [with] the comparator arm in the intent-to- ...

4.

roche.com

roche.com/media/releases/med-cor-2024-11-26

Roche reports update on Phase III SKYSCRAPER-01 study ...

SKYSCRAPER-01 is a global phase III, randomised, double-blind study evaluating tiragolumab plus Tecentriq compared to Tecentriq alone in 534 patients.

5.

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 ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04294810

NCT04294810 | A Study of Tiragolumab in Combination ...

The purpose of the study is to evaluate the efficacy and safety of tiragolumab plus atezolizumab compared with placebo plus atezolizumab in participants ...

7.

targetedonc.com

targetedonc.com/view/tiragolumab-plus-atezolizumab-fails-to-improve-outcomes-as-consolidation-in-nsclc

Tiragolumab Plus Atezolizumab Fails to Improve ...

Tiragolumab plus atezolizumab did not improve progression-free survival compared to durvalumab in stage III NSCLC patients post-cCRT. Median ...