Tiragolumab + Atezolizumab for Advanced Solid Cancer

(SKYSCRAPER-11 Trial)

Recruiting at 38 trial locations

Overseen By Reference Study ID Number: GO44096 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hoffmann-La Roche

Must not be taking: Immunosuppressants, Antibiotics

Disqualifiers: Cardiovascular disease, Liver disease, Diabetes, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Variable (until disease progression or toxicity)

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of two drugs given through an IV to help the immune system fight advanced or hard-to-treat solid tumors. The drugs work by making it easier for immune cells to find and destroy cancer cells. The combination of ipilimumab and nivolumab is frequently investigated to improve cancer treatment outcomes, especially in patients who do not benefit from single-drug treatments.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot have had any anti-cancer therapy within 3 weeks before starting the trial. Also, you should not be on systemic immunosuppressive medications within 2 weeks before the trial begins.

What data supports the effectiveness of the drug combination Tiragolumab and Atezolizumab for advanced solid cancer?

Research shows that Tiragolumab, when combined with Atezolizumab, has shown promising results in treating various solid cancers, especially non-small cell lung cancer. Additionally, this combination has been found to reactivate immune cells in certain colorectal cancer types, suggesting it could help the body's immune system fight cancer more effectively. ^{1 2 3 4 5}

Is the combination of Tiragolumab and Atezolizumab generally safe for humans?

Atezolizumab, when used alone, has shown manageable safety in patients with advanced lung cancer, with serious side effects occurring in a small percentage of patients. Immune-related side effects can happen with treatments like Atezolizumab, but they are generally manageable based on clinical experience. ^{2 3 6 7 8}

How is the drug combination of Tiragolumab and Atezolizumab unique for treating advanced solid cancer?

The combination of Tiragolumab and Atezolizumab is unique because it targets two immune checkpoints, TIGIT and PD-L1, which may enhance the immune system's ability to fight cancer cells. This dual approach has shown promise in reactivating immune responses in cancers that are resistant to other treatments, such as microsatellite stable colorectal cancer. ^{1 2 4 9 10}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with advanced solid tumors that are PD-L1 positive and have not been treated with checkpoint inhibitors before. They should be in good health overall, have a life expectancy of at least 12 weeks, and no severe autoimmune diseases or infections. Women must test negative for pregnancy and agree to contraception; men also need to use birth control.

Inclusion Criteria

I have recovered from side effects of my last treatment, except for hair loss.

Agreement to contraception for female participants of childbearing potential

I agree to use contraception.

Exclusion Criteria

Pregnancy or intention of becoming pregnant

I haven't had major surgery in the last 28 days and don't expect to need one during the study.

History of autoimmune disease

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tiragolumab and atezolizumab as an intravenous fixed dose combination (IV FDC) on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit, or unacceptable toxicity

Variable (until disease progression or toxicity)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Tiragolumab and Atezolizumab IV FDC

Trial Overview The study tests a combination of two drugs, Tiragolumab and Atezolizumab, given together intravenously (IV) to see how safe they are, how the body processes them, and if they cause an immune response against certain types of tumors.

Participant Groups

Group I: Tiragolumab and Atezolizumab IV FDC Experimental Treatment 1 Intervention

Participants will receive tiragolumab and atezolizumab as an intravenous fixed dose combination (IV FDC) on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity.

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

Findings from Research

The combination of atezolizumab (anti-PD-L1) and tiragolumab (anti-TIGIT) was able to reactivate T cells in 46% of microsatellite stable colorectal cancer (MSS-CRC) samples, suggesting a potential new treatment strategy for this resistant cancer type.

Higher baseline levels of Th1 and Tc1 cells, along with increased CD96 expression on T cells, were associated with better reactivation responses, indicating that CD96 could serve as a marker for predicting the efficacy of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting PD-L1 and TIGIT could restore intratumoral CD8 T cell function in human colorectal cancer. Thibaudin, M., Limagne, E., Hampe, L., 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, an immune checkpoint inhibitor, demonstrated significant efficacy in treating advanced solid tumors, particularly showing a non-progression rate of 44.4% in cervical cancer and 54.5% in follicular/papillary thyroid cancer among 474 patients enrolled in a phase II study.

The treatment was generally well-tolerated, with 55.3% of patients experiencing treatment-related adverse events, mostly mild to moderate, indicating a safety profile consistent with previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II multicohort study of atezolizumab monotherapy in multiple advanced solid cancers. Tabernero, J., Andre, F., Blay, JY., 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]

In a study of 158 patients with advanced non-small cell lung cancer, nivolumab showed a slightly higher objective response rate (22.5%) compared to atezolizumab (14.5%), but this difference was not statistically significant (p = 0.140).

Both treatments did not show significant differences in progression-free survival (PFS) and overall survival (OS), but atezolizumab had a more favorable safety profile, with fewer adverse events reported compared to nivolumab (49.3% vs. 76.4%, p < 0.001).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Analysis of Nivolumab and Atezolizumab Efficacy in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer. Alonso-García, M., Sánchez-Gastaldo, A., Muñoz-Fuentes, MA., et al.[2023]

Atezolizumab treatment in 615 patients with previously treated advanced non-small cell lung cancer showed a median overall survival of 11.1 months and a median progression-free survival of 2.7 months, indicating its efficacy in this population.

The safety profile was manageable, with treatment-related serious adverse events occurring in 7.8% of patients and immune-related adverse events in 8.3%, confirming that atezolizumab can be safely administered even to patients with severe renal impairment and other challenging conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary results from TAIL: a global single-arm safety study of atezolizumab monotherapy in a diverse population of patients with previously treated advanced non-small cell lung cancer. Ardizzoni, A., Azevedo, S., Rubio-Viqueira, B., et al.[2021]

Immune checkpoint inhibitors, such as pembrolizumab and nivolumab, can lead to immune-related adverse events (irAEs) due to their mechanism of enhancing the immune response against cancer, which can sometimes mistakenly target healthy tissues.

This study reviewed 128 reports involving 239 cases of toxicities associated with these treatments, highlighting the need for careful management of irAEs, as there is currently no standardized approach based on prospective trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of immune checkpoint inhibitor-related adverse events: A review of case reports. Si, X., Song, P., Ni, J., et al.[2021]

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]

This phase I clinical trial is investigating the safety and efficacy of combining the anti-TIGIT monoclonal antibody tiragolumab with the PD-L1 inhibitor atezolizumab and Stereotactic Body Radiation Therapy (SBRT) in patients with metastatic non-small cell lung cancer and other cancers previously treated with immune checkpoint inhibitors.

The primary goal of the trial is to assess the safety of this combination treatment and to evaluate its effectiveness in improving 6-month progression-free survival (PFS), with the study including multiple cancer types and a focus on immune biomarker assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of the combination of atezolizumab, tiragolumab, and stereotactic body radiation therapy in patients with metastatic multiorgan cancer. Roussot, N., Fumet, JD., Limagne, E., et al.[2023]

Atezolizumab, an anti-PD-L1 therapy, demonstrated objective response rates of up to 40% in non-small cell lung cancer (NSCLC) and showed similar pharmacokinetics and safety profiles in Chinese patients compared to global studies.

In patients with PD-L1 positive tumors, the combination of atezolizumab with chemotherapy resulted in a significantly higher response rate of 46.2%, indicating enhanced efficacy when used alongside traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Atezolizumab therapy in Chinese patients with locally advanced or metastatic solid tumors: An open-label, phase Ⅰ study]. Zhang, L., Gong, JF., Pan, HM., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Targeting PD-L1 and TIGIT could restore intratumoral CD8 T cell function in human colorectal cancer. [2022]

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

Tiragolumab Impresses in Multiple Trials. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Phase II multicohort study of atezolizumab monotherapy in multiple advanced solid cancers. [2022]

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

SKYSCRAPER-02: Tiragolumab in Combination With Atezolizumab Plus Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Real-World Analysis of Nivolumab and Atezolizumab Efficacy in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Primary results from TAIL: a global single-arm safety study of atezolizumab monotherapy in a diverse population of patients with previously treated advanced non-small cell lung cancer. [2021]

7. Singapore pubmed.ncbi.nlm.nih.gov

Management of immune checkpoint inhibitor-related adverse events: A review of case reports. [2021]

8. England 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. [2022]

9. England pubmed.ncbi.nlm.nih.gov

A phase I study of the combination of atezolizumab, tiragolumab, and stereotactic body radiation therapy in patients with metastatic multiorgan cancer. [2023]

10. China pubmed.ncbi.nlm.nih.gov

[Atezolizumab therapy in Chinese patients with locally advanced or metastatic solid tumors: An open-label, phase Ⅰ study]. [2022]