Tiragolumab + Atezolizumab for Non-Small Cell Lung Cancer

(SKYSCRAPER-01 Trial)

Not currently recruiting at 277 trial locations

Overseen By Reference Study ID Number: GO41717 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must be taking: Atezolizumab

Must not be taking: CD137 agonists, Anti-CTLA-4

Disqualifiers: EGFR mutation, ALK translocation, Autoimmune disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: Until disease progression or unacceptable toxicity

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two drugs, tiragolumab and atezolizumab (Tecentriq), to determine if their combination is more effective than atezolizumab alone in treating non-small cell lung cancer (NSCLC). The trial targets individuals whose cancer has spread, cannot be surgically removed, and who have not received other treatments for their metastatic cancer. Participants will receive either both drugs or atezolizumab with a placebo. The trial seeks individuals with high levels of the protein PD-L1 in their cancer, without certain gene mutations or previous treatments for this cancer type. Those with untreated advanced NSCLC and high PD-L1 may be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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

The trial protocol does not specify if you need to stop your current medications, but it does exclude those who have had certain treatments recently, like investigational therapies or specific immune therapies. It's best to discuss your current medications with the trial team.

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

Research shows that the combination of tiragolumab and atezolizumab is under study for its safety in treating non-small cell lung cancer (NSCLC). Studies have found that most patients tolerate this combination well. However, some reports indicate it may not significantly improve survival compared to other treatments. Despite this, safety data suggest the treatment does not cause severe side effects for most patients. As this treatment progresses through later research stages, evidence shows it is safe enough for further study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-small cell lung cancer?

Researchers are excited about the combination of tiragolumab and atezolizumab for non-small cell lung cancer because it introduces a novel approach to treatment. Unlike traditional therapies like chemotherapy, which broadly attack cancer cells, tiragolumab is a monoclonal antibody that targets the TIGIT pathway. This action potentially enhances the immune response against cancer cells when combined with atezolizumab, an immune checkpoint inhibitor that targets the PD-L1 protein. This dual mechanism aims to effectively harness the body's immune system to fight cancer more precisely and might offer improved outcomes compared to existing treatments.

What evidence suggests that tiragolumab plus atezolizumab might be an effective treatment for non-small cell lung cancer?

This trial will compare the combination of tiragolumab and atezolizumab with a placebo and atezolizumab for non-small cell lung cancer (NSCLC). Research has shown that combining tiragolumab with atezolizumab has not clearly improved treatment for NSCLC. Specifically, the SKYSCRAPER-01 study found no significant improvement in delaying cancer progression or extending patients' lives when using both drugs compared to atezolizumab alone. Thus, adding tiragolumab did not effectively stop the cancer from worsening or help patients live longer in that study. However, tiragolumab targets a different part of the immune system, which researchers hope might enhance the body's ability to fight cancer. More research is needed to fully understand its potential benefits. ^{2 3 4 5 6}

Who Is on the Research Team?

Clinical Trial

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 has high PD-L1 expression, no prior treatments for metastatic NSCLC, and no EGFR mutations or ALK translocations. Participants should be in good physical condition (ECOG 0 or 1), have measurable disease, and proper organ function. Exclusions include a history of certain lung diseases, previous immune therapy treatments, active hepatitis B/C, HIV positive status, other cancers within the last 5 years except those with low risk.

Inclusion Criteria

I haven't had any systemic treatment for my advanced lung cancer.

I am fully active or can carry out light work.

My blood and organs are functioning well.

Exclusion Criteria

I have brain metastases that are untreated or getting worse.

My cancer has a known EGFR mutation or ALK fusion.

I haven't taken any immune-boosting drugs in the last 4 weeks or 5 half-lives before starting the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either tiragolumab plus atezolizumab or placebo plus atezolizumab every 3 weeks until disease progression, loss of clinical benefit, or unacceptable toxicity

Until disease progression or unacceptable toxicity

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 59 months

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Tiragolumab

Trial Overview

The study tests the effectiveness and safety of combining Tiragolumab with Atezolizumab versus a placebo combined with Atezolizumab in untreated advanced NSCLC patients selected based on PD-L1 expression. Patients are randomly assigned to either treatment group in equal numbers.

How Is the Trial Designed?

Group I: Tiragolumab + Atezolizumab Experimental Treatment 2 Interventions

Participants will receive atezolizumab followed by tiragolumab every 3 weeks (Q3W) on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity.

Group II: Placebo + Atezolizumab Placebo Group 2 Interventions

Participants will receive atezolizumab followed by placebo Q3W on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity.

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

Published Research Related to This Trial

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]

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 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 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, 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 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]

Citations

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Tiragolumab Plus Atezolizumab Fails to Meet Survival End ...

The SKYSCRAPER-01 trial showed no statistically significant PFS and OS improvements with tiragolumab plus atezolizumab in PD-L1–high NSCLC ...

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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 ...

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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 ...

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.

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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 ...

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targetedonc.com

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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 ...