Tiragolumab + Atezolizumab for Solid Tumors

Not currently recruiting at 43 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Systemic steroids, Immunosuppressants

Disqualifiers: Pregnancy, Active autoimmune, Hepatitis, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 21

Duration: Up to 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of combining two immunotherapy drugs, tiragolumab and atezolizumab (Tecentriq), in treating aggressive solid tumors in children and adults. These tumors, which lack the SMARCB1 or SMARCA4 genes, often resist treatment or recur. The trial drugs are designed to enhance the immune system's ability to attack these resilient cancer cells and inhibit their growth. Suitable candidates for this trial have tumors missing the SMARCB1 or SMARCA4 genes and have not responded to other treatments. As a Phase 1/Phase 2 trial, this research seeks to understand the treatment's effects and measure its initial effectiveness, allowing participants to contribute to groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before enrolling. You must not be on systemic steroid medications, other anti-cancer agents, or systemic immunosuppressive medications during the study. If you are on these medications, you need to stop them at least 14 days before enrolling.

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

Research shows that tiragolumab and atezolizumab are generally safe when used together. In a study with 20 patients, these treatments were combined, and researchers found no new safety issues. This indicates no unexpected side effects beyond what is already known about each drug individually.

Another study confirmed that tiragolumab, whether used alone or with atezolizumab, is well tolerated. Patients did not experience any new or unusual side effects.

These findings suggest that using tiragolumab and atezolizumab together is safe for people, based on current data. This evidence comes from earlier studies, providing participants with more confidence in the treatment's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of tiragolumab and atezolizumab for solid tumors because this treatment duo targets the PD-1/PD-L1 and TIGIT pathways, which play key roles in helping tumors evade the immune system. Unlike traditional chemotherapy that kills rapidly dividing cells, this combo leverages the body's own immune defenses to attack cancer cells. Atezolizumab is a known immune checkpoint inhibitor that blocks PD-L1, while tiragolumab is a novel anti-TIGIT antibody, both working together to enhance the immune response against tumors. This dual mechanism offers a promising new avenue for patients, especially those who may not respond well to existing treatments.

What evidence suggests that this trial's treatments could be effective for SMARCB1 or SMARCA4 deficient tumors?

Research has shown that combining tiragolumab with atezolizumab may help treat certain cancers. In this trial, participants will receive both tiragolumab and atezolizumab. Studies have found this combination effective for patients with non-small cell lung cancer and esophageal cancer who have not previously undergone immunotherapy. It improved tumor response and increased survival rates more than atezolizumab alone. Early results also suggest these treatments are generally well-tolerated, causing few unexpected side effects. This makes them a promising option for hard-to-treat tumors lacking the SMARCB1 or SMARCA4 genes. ^{3 4 6 7 8}

Who Is on the Research Team?

Mary F. Wedekind Malone

Principal Investigator

Pediatric Early Phase Clinical Trial Network

Are You a Good Fit for This Trial?

This trial is for children and adults with specific aggressive cancers that lack SMARCB1 or SMARCA4 genes. Participants must have recovered from previous cancer treatments, not received certain therapies recently, and have measurable disease. It's open to those aged 12 months and older (under 18 for part A; no upper age limit for part B), who haven't had TIGIT therapy, are not on systemic steroids, and meet blood count and organ function criteria.

Inclusion Criteria

My tumor lacks SMARCB1 (INI1) or SMARCA4, confirmed by a certified lab test.

I have recovered from side effects of previous cancer treatments.

I haven't had certain medications or live vaccines in the last 30 days.

Exclusion Criteria

I do not have any active autoimmune diseases, infections like TB, hepatitis B or C, recent EBV, HIV, serious heart issues, recent major surgeries, specific lung conditions, uncontrolled effusions or infections, prior organ transplants, and can follow safety monitoring.

Pregnant or breast-feeding women

You are allergic to certain ingredients.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive tiragolumab and atezolizumab intravenously every 21 days for up to 5 years, with imaging scans and blood sample collection

Up to 5 years

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion at months 3, 6, 9, 12, 18, 24, 36, 48, and 60

Up to 5 years

Follow-up visits at specified months

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Tiragolumab

Trial Overview The trial tests tiragolumab plus atezolizumab in patients with relapsed or refractory tumors lacking the SMARCB1/SMARCA4 genes. This study aims to see if these immunotherapy drugs can help the immune system fight cancer more effectively by preventing tumor growth.

How Is the Trial Designed?

Group I: Part A (atezolizumab, tiragolumab) Experimental Treatment 9 Interventions

Patients receive tiragolumab IV over 30-90 minutes on day 1 of each cycle and atezolizumab IV over 30-60 minutes on day 1 of each cycle starting in cycle 2. Treatment repeats every 21 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients undergo standard imaging scans including x-rays, CT, MRI, and/or FDG PET-CT, throughout the trial. Patients also undergo ECHO during screening and blood sample collection on study.

Group II: Arm B (atezolizumab, tiragolumab) Experimental Treatment 8 Interventions

Patients receive atezolizumab IV over 30-60 minutes on day 1 and tiragolumab IV over 30-90 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients also undergo standard imaging scans including x-rays, CT, MRI, and/or FDG PET-CT throughout the trial. Patients also undergo ECHO during screening and blood sample collection on study.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

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, 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 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]

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]

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 is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

Atezolizumab, an anti-PD-L1 therapy, showed long-term safety and efficacy in patients with metastatic urothelial carcinoma, with a median follow-up of 37.8 months and a low incidence of severe treatment-related adverse events (9%).

The treatment resulted in a 26% objective response rate, with a median duration of response of 22.1 months, and median overall survival of 10.1 months, particularly benefiting patients with higher PD-L1 expression on immune cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab (MPDL3280A) Monotherapy for Patients With Metastatic Urothelial Cancer: Long-term Outcomes From a Phase 1 Study. Petrylak, DP., Powles, T., Bellmunt, J., 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]

In the phase III IMagyn050 trial involving patients with newly diagnosed ovarian cancer, the addition of atezolizumab to standard chemotherapy did not improve progression-free survival (PFS) in patients with BRCA1/2 mutations or homologous recombination deficiency (HRD).

Despite the presence of BRCA1/2 mutations or HRD, most ovarian tumors exhibited low tumor mutation burden (TMB), indicating that genomic instability does not predict enhanced sensitivity to immune checkpoint inhibitors like atezolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of Genomic Landscape on Cancer Immunotherapy for Newly Diagnosed Ovarian Cancer: Biomarker Analyses from the IMagyn050 Randomized Clinical Trial. Landen, CN., Molinero, L., Hamidi, H., et al.[2023]

Citations

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Anti-TIGIT Antibody Tiragolumab Alone or With Atezolizumab ... In this nonrandomized controlled trial, tiragolumab was well tolerated with or without atezolizumab; no new safety signals were observed.

2. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2810007

Anti-TIGIT Antibody Tiragolumab Alone or With ... Combination tiragolumab plus atezolizumab showed promising activity in patients with immunotherapy-naive non–small cell lung cancer and esophageal cancer.

3. onclive.com onclive.com/view/skyscraper-05-data-confirm-surgical-feasibility-after-perioperative-tiragolumab-combo-in-nsclc

SKYSCRAPER-05 Data Confirm Surgical Feasibility After ... Perioperative tiragolumab and atezolizumab, with or without chemotherapy, showed surgical feasibility and safety in resectable NSCLC, achieving ...

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

SKYSCRAPER-02: Tiragolumab in Combination With ... The combination was well tolerated and showed clinically meaningful improvements in antitumor response, PFS, and OS versus atezolizumab alone, ...

5. roche.com roche.com/investors/updates/inv-update-2021-12-10

New data from the phase II CITYSCAPE trial show ... After 2.5 years median follow-up, tiragolumab plus Tecentriq continued to show an improvement in the intention-to-treat (ITT) population (n=67), ...

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Phase I pharmacokinetic, safety, and preliminary efficacy ... Results: In this study, 20 patients received a median of five doses of tiragolumab plus atezolizumab. Median age was 57.5 years, 85.0% of ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05661578

NCT05661578 | A Study to Evaluate the Safety and ... The purpose of this study is to assess the safety, pharmacokinetics, and immunogenicity of tiragolumab and atezolizumab intravenous fixed-dose combination ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02794571

Study Details | NCT02794571 | Safety and ... Phase I pharmacokinetic, safety, and preliminary efficacy study of tiragolumab in combination with atezolizumab in Chinese patients with advanced solid tumors.