Atezolizumab + Tiragolumab for Rare Cancers

Not currently recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Anti-TIGIT

Disqualifiers: Autoimmune disease, Active infections, 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: 21

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of two drugs, atezolizumab and tiragolumab, in treating rare solid-tumor cancers that have advanced or spread. These drugs are a type of immunotherapy, which helps the body's immune system fight cancer. Patients with rare solid tumors unresponsive to other treatments might be suitable for this trial. Participants must provide tumor and blood samples to help researchers understand the treatment's effects on the body and identify which patients might benefit most in the future. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering patients a chance to contribute to groundbreaking cancer therapy advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take certain medications like systemic immunosuppressive drugs within 2 weeks before starting the trial. It's best 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 people. One study found this treatment tolerable and even showed early signs of tumor reduction. Its safety was similar to other treatments. In another study, participants continued the treatment for about 7.5 months, indicating manageable side effects.

Although this combination did not consistently improve survival rates in other studies, its safety profile remains promising for those considering a clinical trial. Always consult a healthcare provider to understand the potential risks and benefits for your specific situation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of atezolizumab and tiragolumab because it offers a novel approach to treating rare cancers. Unlike many standard treatments that focus solely on targeting cancer cells, this duo works by enhancing the immune system's ability to recognize and attack tumors. Atezolizumab is a checkpoint inhibitor that blocks the PD-L1 pathway, while tiragolumab targets the TIGIT protein, another immune checkpoint. This dual mechanism may provide a more comprehensive immune response, potentially improving outcomes for patients who have limited options with existing therapies.

What evidence suggests that atezolizumab and tiragolumab might be an effective treatment for rare cancers?

Research has shown that combining atezolizumab with tiragolumab might help treat certain cancers. In earlier studies, this combination was generally safe and showed initial signs of tumor reduction. However, in some cases, it did not extend survival compared to atezolizumab alone, particularly in lung cancer patients with high levels of the protein PD-L1. Despite mixed early results, this trial will investigate whether the combination of atezolizumab and tiragolumab can benefit patients with rare solid tumors. ^{2 3 4 5 6}

Who Is on the Research Team?

Jibran Ahmed

Principal Investigator

National Cancer Institute LAO

Are You a Good Fit for This Trial?

Adults with advanced rare solid tumors that have progressed after standard therapy or lack a standard treatment. They must be willing to undergo biopsies, not qualify for higher priority trials, and have measurable disease. Key health criteria include stable organ function and controlled HIV or hepatitis if present. Pregnant women are excluded, and participants must agree to use contraception.

Inclusion Criteria

My rare solid tumor has not responded to standard treatments or there are none available.

My tumor can be safely biopsied.

My kidney function, measured by creatinine levels or clearance, is within the required range.

Exclusion Criteria

Pregnant women

I do not have any severe illnesses that would stop me from following the study's requirements.

I have recovered from major side effects of my last cancer immunotherapy.

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 intravenously on day 1 of each cycle, with cycles repeating every 21 days in the absence of disease progression or unacceptable toxicity. Biopsies, CT scans, and blood samples are collected throughout the study.

Up to 2 years

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, including adverse events and tumor response.

30 days

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Tiragolumab

Trial Overview The trial is testing the effectiveness of combining two immunotherapy drugs, Atezolizumab and Tiragolumab, in shrinking advanced stage rare solid tumors. It includes taking tissue samples before and after treatment to study the immune response against cancer.

How Is the Trial Designed?

Group I: Treatment (atezolizumab, tiragolumab) Experimental Treatment 6 Interventions

Patients receive atezolizumab IV over 60 minutes and tiragolumab IV over 30-90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO at baseline, undergo biopsy at baseline and on study, and undergo CT and collection of blood samples throughout the 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

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 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]

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]

Atezolizumab (Tecentriq) is an FDA-approved treatment for unresectable or metastatic alveolar soft part sarcoma (ASPS), showing a 24% overall response rate in a clinical trial with 49 patients, and a durable response rate of 67% at 6 months and 42% at 12 months.

The treatment has a manageable safety profile, with common severe side effects including musculoskeletal pain (8%) and hypertension (6%), making it a viable option for patients with limited treatment alternatives for this high-risk disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab as the First Systemic Therapy Approved for Alveolar Soft Part Sarcoma. Bergsma, EJ., Elgawly, M., Mancuso, D., et al.[2023]

Atezolizumab, combined with nab-paclitaxel, significantly improved progression-free survival in patients with advanced triple-negative breast cancer (TNBC) compared to placebo, based on the phase III IMpassion130 trial involving patients with unresectable locally advanced or metastatic TNBC.

While the combination therapy showed a tolerable safety profile, with common side effects like neutropenia and immune-related adverse events, it did not significantly affect health-related quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab (in Combination with Nab-Paclitaxel): A Review in Advanced Triple-Negative Breast Cancer. Kang, C., Syed, YY.[2020]

Atezolizumab, an inhibitor of PD-L1, was found to be well tolerated in a phase 1-2 trial involving 90 children and young adults with refractory or relapsed solid tumors, with no fatal adverse events reported.

While only 5% of patients achieved an objective response, the study showed comparable serum concentrations of atezolizumab between children and young adults, suggesting potential for future research into optimizing immune checkpoint inhibitors for specific patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for children and young adults with previously treated solid tumours, non-Hodgkin lymphoma, and Hodgkin lymphoma (iMATRIX): a multicentre phase 1-2 study. Geoerger, B., Zwaan, CM., Marshall, LV., et al.[2020]

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]

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 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]

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®): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. Bernard-Tessier, A., Bonnet, C., Lavaud, P., et al.[2019]

Citations

1. 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.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05715281

Testing the Combination of Anti-cancer Drugs ... This phase II trial tests how well atezolizumab works in combination with tiragolumab in treating patients with rare solid tumors that may have spread from ...

3. gene.com gene.com/media/press-releases/14937/2021-12-10/new-data-from-the-phase-ii-cityscape-tri

Genentech: Press Releases | Friday, Dec 10, 2021 After 2.5 years median follow-up, tiragolumab plus Tecentriq continued to show an improvement in the intention-to-treat (ITT) population (n=67), ...

4. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT051/761657/Abstract-CT051-SKYSCRAPER-01-A-phase-III

Abstract CT051: SKYSCRAPER-01: A phase III, randomized ... Tiragolumab (tira) + atezolizumab (atezo) has shown encouraging survival outcomes in pts with metastatic NSCLC, primarily in pts with PD-L1 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11258083/

Phase I pharmacokinetic, safety, and preliminary efficacy ... In this study, tiragolumab plus atezolizumab was tolerable and demonstrated preliminary anti-tumor activity. There were no meaningful differences in the PK or ...

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

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