Atezolizumab + Tiragolumab for Lung Cancer

(SKYSCRAPER-03 Trial)

No longer recruiting at 375 trial locations

Overseen By GO41854 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: Immunosuppressants

Disqualifiers: Stage IV NSCLC, Autoimmune disease, EGFR mutation, ALK fusion, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 13

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, atezolizumab (an immunotherapy drug) and tiragolumab, to evaluate their combined effectiveness compared to durvalumab in patients with Stage III non-small cell lung cancer (NSCLC) that cannot be surgically removed. The trial focuses on patients who have completed at least two cycles of a specific chemotherapy and radiation regimen, with cancer that has not progressed further. Suitable candidates are those who have recently finished this treatment and whose cancer remains stable. As a Phase 3 trial, it represents the final step before FDA approval, providing patients access to potentially groundbreaking treatments.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it does exclude participants who are on systemic immunosuppressive medication, so you may need 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 atezolizumab and tiragolumab is generally safe for patients. In some studies, this combination did not cause any new or unexpected side effects beyond those already known for each drug.

Atezolizumab is already approved for other uses, indicating that its safety profile is well understood. When tiragolumab was added to atezolizumab, certain studies found no additional side effects, which is a positive sign for safety.

Like any treatment, side effects can occur. However, reports so far suggest that patients can tolerate this drug combination without major problems. Always consult a healthcare provider for advice tailored to individual needs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of atezolizumab and tiragolumab for lung cancer because it offers a fresh approach to stimulating the immune system. Atezolizumab is a PD-L1 inhibitor, which helps the immune system recognize and attack cancer cells. Tiragolumab is unique because it targets a different immune checkpoint, TIGIT, which further enhances the immune response against tumors. This dual-action strategy could potentially offer better control of the disease compared to current treatments that typically focus on a single immune checkpoint.

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

This trial will compare the combination of atezolizumab and tiragolumab with durvalumab for treating non-small cell lung cancer (NSCLC). Research has shown that using atezolizumab and tiragolumab together holds promise for treating NSCLC. Some studies found that this combination helped patients live longer. However, other research indicated that it did not prevent cancer progression more effectively than atezolizumab alone in certain groups. Overall, while there is potential, the results have been mixed, and further research is needed to confirm its effectiveness. ^{3 6 7 8 9}

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 Stage III non-small cell lung cancer (NSCLC) who've had some chemo and radiation but no disease progression. They need to be in good health overall, not pregnant, willing to use contraception, and have a life expectancy of at least 12 weeks. People can't join if they've had certain previous treatments for NSCLC or other cancers, specific gene mutations in their cancer, unresolved side effects from past treatments, autoimmune diseases, or are on immunosuppressive drugs.

Inclusion Criteria

You are expected to live for at least 12 weeks.

My lung cancer is at an advanced stage and cannot be removed by surgery.

I will not donate sperm during and for 3 months after treatment.

Exclusion Criteria

I am taking medication that weakens my immune system.

I have been newly diagnosed with Stage III lung cancer that cannot be surgically removed.

My NSCLC has an EGFR mutation or ALK fusion.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atezolizumab and tiragolumab or durvalumab intravenously every 28 days for up to 13 cycles

52 weeks

13 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 114 months

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Durvalumab
• Tiragolumab

Trial Overview The study tests the effectiveness and safety of combining two drugs: Atezolizumab and Tiragolumab versus Durvalumab alone. All participants previously received platinum-based chemoradiotherapy without their cancer getting worse. The goal is to see which combination works better after this initial treatment.

How Is the Trial Designed?

Group I: Atezolizumab + Tiragolumab Experimental Treatment 2 Interventions

Participants will receive atezolizumab administered intravenously (IV) on Day 1 of each 28-day cycle followed by tiragolumab administered IV on Day 1 of each 28-day cycle for a maximum of 13 cycles.

Group II: Durvalumab Active Control 1 Intervention

Participants will receive durvalumab administered IV during each 28-day cycle for a maximum of 13 cycles.

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

Durvalumab, an immunotherapy drug for non-small cell lung cancer (NSCLC), has shown significant activity and acceptable tolerability, especially in patients with at least 25% PD-L1 tumor expression, and has been established as a standard treatment following chemoradiation based on the PACIFIC study results.

While durvalumab is effective in wild-type EGFR and ALK patients, its efficacy is lower in those with EGFR mutations or ALK-positive status, highlighting the need for ongoing research into combination therapies and the management of treatment-related toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. Mezquita, L., Planchard, D.[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]

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]

Immunotherapy is becoming a key part of first-line treatment for non-small cell lung cancer (NSCLC), with various phase 3 studies showing the effectiveness of drugs targeting PD-1, PD-L1, and CTLA-4, often in combination with chemotherapy.

Patients with high PD-L1 expression (≥ 50%) can be treated with single-agent Pembrolizumab or Atezolizumab, while those with lower expression have multiple treatment options, including combinations of immunotherapy and chemotherapy, highlighting the tailored approach based on tumor characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First line Immunotherapy for Non-Small Cell Lung Cancer. Nasser, NJ., Gorenberg, M., Agbarya, A.[2020]

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]

In a study of 83 patients with unresectable stage III non-small cell lung cancer (NSCLC) receiving durvalumab, 25.3% experienced pneumonitis, confirming the risk associated with this treatment.

The incidence of pneumonitis observed in this real-world setting aligns with findings from the PACIFIC trial, indicating that the safety profile of durvalumab is consistent in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Incidence of Pneumonitis in Patients Receiving Durvalumab. LeClair, JN., Merl, MY., Cohenuram, M., 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, the first anti-PD-L1 monoclonal antibody approved by the FDA, has shown promising efficacy in treating metastatic triple-negative breast cancer, supported by data from the Phase III IMpassion130 trial.

The review highlights the pharmacodynamic and pharmacokinetic properties of atezolizumab, emphasizing its safety and effectiveness in various cancers, including small-cell lung cancer and renal cell cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. Mavratzas, A., Seitz, J., Smetanay, K., et al.[2020]

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]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.01363

SKYSCRAPER-02: Tiragolumab in Combination With ... Tiragolumab did not provide additional benefit over atezolizumab and CE in untreated ES-SCLC. The combination was well tolerated with no new safety signals.

2. lungcancerstoday.com lungcancerstoday.com/post/final-survival-results-from-phase-3-skyscraper-01-study-presented-at-aacr-2025

Phase 3 SKYSCRAPER-01 Study: Final PFS, OS Analyses ... Dr. Peters and colleagues explained that the combination of tiragolumab plus atezolizumab “has shown encouraging survival outcomes” in patients ...

3. 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.

4. 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 ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35576957/

Tiragolumab plus atezolizumab versus placebo ... Median progression-free survival was 5·4 months (95% CI 4·2-not estimable) in the tiragolumab plus atezolizumab group versus 3·6 months (2·7-4·4) ...

6. 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.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37976444/

SKYSCRAPER-02: Tiragolumab in Combination ... - PubMed Tiragolumab did not provide additional benefit over atezolizumab and CE in untreated ES-SCLC. The combination was well tolerated with no new ...

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

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

9. 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 ...