Atezolizumab +/− Tiragolumab for Esophageal Cancer

(SKYSCRAPER-07 Trial)

Recruiting at 283 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

760 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy and safety of tiragolumab plus atezolizumab compared with placebo in participants with unresectable esophageal squamous cell carcinoma (or those who are unable or unwilling to undergo surgery) and whose cancers have not progressed following definitive concurrent chemoradiotherapy (dCRT). Participants will be randomized in a 1:1:1 ratio to receive either tiragolumab plus atezolizumab (Arm A), tiragolumab matching placebo plus atezolizumab (Arm B), or double placebo (Arm C).

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.

What data supports the effectiveness of the drug Atezolizumab for esophageal cancer?

Atezolizumab has shown effectiveness in other cancers, like bladder cancer, where it improved survival rates and had a favorable safety profile. Additionally, when combined with tiragolumab, it showed promising results in solid cancers, suggesting potential benefits for esophageal cancer as well. ^{1 2 3 4 5}

Is Atezolizumab safe for use in humans?

Atezolizumab, used in combination with other treatments, has been studied for safety in various cancers, including esophageal cancer. It is generally considered safe, but like many cancer treatments, it can cause side effects, which may include immune-related reactions. The safety profile of Atezolizumab is similar to other immune checkpoint inhibitors, with most patients experiencing some level of treatment-related adverse events. ^{6 7 8 9 10}

How is the drug Atezolizumab +/− Tiragolumab unique for esophageal cancer?

Atezolizumab and Tiragolumab are unique because they target the immune system to fight cancer, with Atezolizumab blocking a protein called PD-L1 and Tiragolumab targeting another protein called TIGIT, potentially enhancing the immune response against esophageal cancer. ^{5 11 12 13 14}

Research Team

Clinical Trial

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

[Atezolizumab (Tecentriq&#174;): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. [2019]

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

Tiragolumab Impresses in Multiple Trials. [2021]

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

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]

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

A PERFECT Biomarker-focused Study of Neoadjuvant IO for Esophagogastric Cancer. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

The combination of gene hyperamplification and PD-L1 expression as a biomarker for the clinical benefit of tislelizumab in gastric/gastroesophageal junction adenocarcinoma. [2022]

6. China pubmed.ncbi.nlm.nih.gov

Biologic therapy in esophageal and gastric malignancies: current therapies and future directions. [2020]

7. China 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). [2022]

8. Switzerland 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. [2023]

9. Netherlands 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. [2023]

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

Perioperative Atezolizumab Plus Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel for Resectable Esophagogastric Cancer: Interim Results From the Randomized, Multicenter, Phase II/III DANTE/IKF-s633 Trial. [2023]

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

Tislelizumab Plus Chemotherapy as First-line Treatment for Advanced Esophageal Squamous Cell Carcinoma and Gastric/Gastroesophageal Junction Adenocarcinoma. [2021]

12. Italy pubmed.ncbi.nlm.nih.gov

Nimotuzumab with cisplatin or fluorouracil on human esophageal squamous cell carcinoma EC1 cells. [2019]

13. United States 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. [2022]

14. United States 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. [2022]