Atezolizumab +/− Tiragolumab for Esophageal Cancer

(SKYSCRAPER-07 Trial)

Not currently recruiting at 331 trial locations

Overseen By Reference Study ID Number: YO42137 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: CD137 agonists, Immune checkpoint blockers

Disqualifiers: Autoimmune disease, Pneumonitis, Other malignancies, 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: Unknown

Duration: Up to approximately 6 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two immunotherapy drugs, atezolizumab and tiragolumab, for individuals with esophageal squamous cell carcinoma that cannot be surgically removed. Researchers aim to determine if these drugs can control cancer after patients complete standard chemoradiotherapy. Participants will be randomly assigned to one of three groups: both drugs, atezolizumab with a placebo, or a double placebo. This trial may suit those diagnosed with esophageal squamous cell carcinoma that cannot be surgically removed and who have completed chemoradiotherapy without cancer progression. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer treatment advancements.

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 atezolizumab and tiragolumab is generally well-tolerated by patients. In one study, most participants experienced only mild to moderate side effects. Over 90% of patients across different study groups had some side effects, but these were mostly manageable.

Atezolizumab, already approved for treating other cancers, has been found safe when used alone. Studies have demonstrated a good safety record in people with esophageal cancer, with mostly mild side effects.

Overall, while side effects are common, they are usually not severe. This makes the treatment a potential option for those considering joining a clinical trial, as the safety data appears promising. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about atezolizumab and tiragolumab for esophageal cancer because they work differently than traditional chemotherapy and radiation treatments. Atezolizumab is an immunotherapy that blocks the PD-L1 protein, helping the immune system recognize and attack cancer cells more effectively. Tiragolumab is another immunotherapy that targets the TIGIT protein, aiming to further enhance the immune response against cancer. This dual approach of targeting both PD-L1 and TIGIT is promising because it could boost the body's natural defenses in a way that current standard treatments do not, potentially leading to better outcomes for patients.

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

Research has shown that atezolizumab, one of the treatments in this trial, has promising effects for patients with esophageal cancer when used after chemoradiotherapy. In some studies, patients lived for a median of 31 months, with favorable rates of time without cancer progression. In this trial, some participants will receive atezolizumab alone, while others will receive a combination of atezolizumab and tiragolumab. Previous studies have shown that adding tiragolumab to atezolizumab holds even more promise. This combination significantly improved patient survival when used with chemotherapy. It also increased the number of patients who responded to treatment and extended the time they lived without cancer progression compared to other treatments. These findings suggest that the treatments under study could be effective for esophageal cancer. ^{1 2 3 4 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 esophageal squamous cell carcinoma that can't be removed by surgery and hasn't worsened after chemoradiotherapy. They must have good physical function, no serious unresolved side effects from prior treatments, no autoimmune diseases or recent other cancers, and agree to contraception.

Inclusion Criteria

Women of childbearing potential must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period, for 5 months after the final dose of atezolizumab/placebo, and for 90 days after the final dose of tiragolumab/placebo, whichever is later

I am fully active or can carry out light work.

My cancer cannot be removed by surgery, as confirmed by a specialist.

Exclusion Criteria

I haven't had cancer, other than esophageal, in the last 2 years.

I have previously received treatments targeting the immune system.

I have not received any experimental treatments for esophageal cancer.

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, tiragolumab matching placebo plus atezolizumab, or double placebo

Up to approximately 6 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 6 years

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Atezolizumab Matching Placebo
• Tiragolumab
• Tiragolumab Matching Placebo

Trial Overview

The study tests the effectiveness of Tiragolumab with Atezolizumab versus placebo in patients. Participants are randomly assigned to one of three groups: both drugs, one drug plus placebo, or double placebo to compare outcomes.

How Is the Trial Designed?

Group I: Arm B: Tiragolumab Placebo + Atezolizumab Experimental Treatment 2 Interventions

Participants will receive atezolizumab followed by tiragolumab matching placebo.

Group II: Arm A: Tiragolumab + Atezolizumab Experimental Treatment 2 Interventions

Participants will receive atezolizumab followed by tiragolumab.

Group III: Arm C: Tiragolumab Placebo + Atezolizumab Placebo Placebo Group 2 Interventions

Participants will receive matching placebos to tiragolumab and atezolizumab.

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

In a phase II trial involving 20 patients with locally advanced esophageal squamous cell carcinoma (ESCC), toripalimab combined with docetaxel and cisplatin showed a promising objective response rate of 70%, indicating significant efficacy as a neoadjuvant therapy.

The treatment was found to be safe, with common adverse events including leucopenia and immune dermatitis, but no treatment-related deaths or significant delays in surgery, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toripalimab combined with docetaxel and cisplatin neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma: a single-center, single-arm clinical trial (ESONICT-2). Gao, L., Lu, J., Zhang, P., et al.[2022]

In a Phase II clinical trial involving 63 patients with advanced esophageal cancer, the combination of nimotuzumab (an anti-EGFR antibody) with chemotherapy and radiation was found to be very well tolerated, indicating a favorable safety profile.

The treatment resulted in a significantly higher objective response rate of 47.8% in the nimotuzumab group compared to 15.4% in the control group, particularly benefiting patients with tumors that overexpress the EGFR, suggesting enhanced efficacy in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of malignant, non-resectable, epithelial origin esophageal tumours with the humanized anti-epidermal growth factor antibody nimotuzumab combined with radiation therapy and chemotherapy. Ramos-Suzarte, M., Lorenzo-Luaces, P., Lazo, NG., et al.[2022]

In a systematic review of 5595 patients from 10 clinical trials, PD-1 blockade therapies for advanced esophageal cancer showed high rates of treatment-related adverse events (TRAEs), with 88% experiencing any grade of TRAEs and 24% experiencing grade 3 or higher TRAEs when treated with PD-1 blockade alone.

When compared to chemotherapy, PD-1 blockade therapies had similar rates of all grade TRAEs (RR 0.96) and lower rates of grade 3 or higher TRAEs (RR 0.75), suggesting that PD-1 blockade may be a safer option for patients with advanced esophageal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of treatment-related adverse events of PD-1 blockade-based therapies in advanced esophageal cancer: A systematic review and meta-analysis. Luo, Y., Yao, Y., Wu, P., et al.[2023]

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]

In a meta-analysis of 1231 patients, pembrolizumab and paclitaxel showed no significant difference in effectiveness for treating advanced gastroesophageal cancer, with similar objective response rates.

Both treatments can be considered viable options for patients, as they provide comparable time to response and similar rates of partial response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus paclitaxel for previously treated, advanced gastro-esophageal junction cancer: A systematic review and meta-analysis of randomized clinical trials. Swed, S., Shaheen, N., Hafez, W., et al.[2022]

A systematic review of 11 randomized controlled trials involving patients with esophageal cancer (EPC) and gastroesophageal junction cancer (GEJC) found that immune checkpoint inhibitors (ICIs) have a similar risk of severe treatment-related adverse events (trAEs) compared to chemotherapy, with a risk ratio of 0.764.

While ICIs were associated with a higher incidence of immune-related adverse events (irAEs) compared to chemotherapy (7.35% vs. 2.25%), the overall rates of these events were considered low and manageable, highlighting the importance of monitoring for specific adverse effects in patients receiving ICIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment- and immune-related adverse events of immune checkpoint inhibitors in esophageal or gastroesophageal junction cancer: A network meta-analysis of randomized controlled trials. Zheng, J., Huang, B., Xiao, L., et al.[2023]

Biologic therapies, particularly those targeting HER2 and VEGF, are showing promise in treating esophageal and gastric cancers, with trastuzumab and ramucirumab currently recommended by the NCCN for specific patient groups.

Recent studies indicate that other agents like pertuzumab, apatinib, and pembrolizumab may improve overall and progression-free survival, suggesting a growing role for targeted biologic therapies in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologic therapy in esophageal and gastric malignancies: current therapies and future directions. Samson, P., Lockhart, AC.[2020]

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]

Nimotuzumab (h-R3) showed a weak inhibitory effect on the proliferation of human esophageal squamous cell carcinoma (ESCC) EC1 cells, with a maximum inhibition rate of only 10.10% after 48 hours, indicating limited efficacy as a standalone treatment.

Combining h-R3 with chemotherapeutic agents like cisplatin or fluorouracil did not significantly enhance the inhibition of cell growth or increase apoptosis rates compared to the chemotherapeutic agents alone, suggesting that h-R3 may not provide additional benefits in treating ESCC in vitro.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nimotuzumab with cisplatin or fluorouracil on human esophageal squamous cell carcinoma EC1 cells. Ji, YH., Yang, XY., Wu, JQ., et al.[2019]

Atezolizumab, a monoclonal antibody targeting PD-L1, showed a 23% response rate and a median overall survival of 15.9 months in 119 patients with metastatic urothelial cancer who were unfit for cisplatin, indicating its efficacy as a front-line treatment.

In patients whose tumors progressed after first-line chemotherapy, atezolizumab had a 15% response rate and a median overall survival of 7.9 months, with better outcomes (26% response rate) in those with high PD-L1 expression, demonstrating its potential effectiveness based on biomarker status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Atezolizumab (Tecentriq&#174;): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. Bernard-Tessier, A., Bonnet, C., Lavaud, P., et al.[2019]

In a phase II study involving 30 patients with advanced esophageal squamous cell carcinoma (ESCC) or gastric/gastroesophageal junction (G/GEJ) adenocarcinoma, the combination of tislelizumab and chemotherapy showed a confirmed objective response rate (ORR) of 46.7% and a disease control rate (DCR) of 80%.

The treatment was generally well-tolerated, with manageable side effects, although one patient experienced severe hepatic dysfunction; the median duration of response for ESCC was 12.8 months, indicating promising durability of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab Plus Chemotherapy as First-line Treatment for Advanced Esophageal Squamous Cell Carcinoma and Gastric/Gastroesophageal Junction Adenocarcinoma. Xu, J., Bai, Y., Xu, N., et al.[2021]

Citations

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nature.com/articles/s43018-025-00918-1

a multicenter phase 2 trial (EPOC1802)

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cancernetwork.com

cancernetwork.com/view/atezolizumab-after-chemoradiotherapy-elicits-promising-responses-in-escc

Atezolizumab After Chemoradiotherapy Elicits Promising ...

The median progression-free survival (PFS) was 3.2 months, and the 12-month PFS rate was 29.6%. The median overall survival (OS) was 31.0 months ...

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pubmed.ncbi.nlm.nih.gov/38709220/

Phase II Study to Determine the Antitumor Activity and ...

The median progression-free survival was 1.9 months (95% CI, 1.8-3.7). Analysis of response by PDL1 expression (Ventana SP263) resulted in an ...

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targetedonc.com

targetedonc.com/view/neoadjuvant-atezolizumab-and-chemo-show-potential-in-gastric-gej-cancer

Neoadjuvant Atezolizumab and Chemo Show Potential in ...

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Phase II Study to Determine the Antitumor Activity and Safety ...

In this study, we report the results from the esophageal squamous cell carcinoma (SCC) cohort of a phase II, noncomparative, basket study ...