Tiragolumab + Atezolizumab + Bevacizumab for Non-Small Cell Lung Cancer

Not currently recruiting at 2 trial locations

Overseen By Jenny Crawford

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Georgetown University

Must not be taking: Anti-TIGIT, Anti-viral, Aspirin, others

Disqualifiers: CNS metastases, Autoimmune disease, Hypertension, 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: 3

Duration: 9 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of three drugs—tiragolumab, atezolizumab (an immunotherapy drug also known as Tecentriq), and bevacizumab (also known as Avastin)—to determine their effectiveness in treating advanced non-squamous non-small cell lung cancer (NSCLC). The goal is to assess the efficacy of these drugs in patients whose cancer has progressed despite previous treatments. Individuals with advanced NSCLC that has worsened after treatments and who have specific genetic profiles might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not be on certain treatments like systemic immunosuppressive medications or high-dose aspirin close to the start of 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 tiragolumab, atezolizumab, and bevacizumab has been tested in various studies. In some studies, this combination did not significantly improve certain cancer outcomes, such as progression-free survival and overall survival. However, these studies provided valuable safety information.

Atezolizumab and bevacizumab are already approved for other uses, providing some safety data. These drugs are generally well-tolerated, but they can have side effects, such as fatigue, high blood pressure, or minor bleeding.

Tiragolumab, a newer drug, is still under investigation in different trials. So far, no major safety concerns have emerged, but its safety profile is less established compared to the other two drugs.

This trial is in phase 2, indicating that earlier phases found the treatment reasonably safe, but more information is needed to confirm this. Participants should consider these points and consult their doctor if they have any concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Tiragolumab, Atezolizumab, and Bevacizumab for non-small cell lung cancer because it targets the cancer in a unique way. Unlike traditional treatments like chemotherapy, which attack rapidly dividing cells, this combination includes Tiragolumab, an innovative immune checkpoint inhibitor that blocks a protein called TIGIT. This action helps the immune system better recognize and destroy cancer cells. The addition of Atezolizumab, another immune checkpoint inhibitor targeting PD-L1, and Bevacizumab, which inhibits blood vessel growth to tumors, creates a multi-faceted approach that could enhance treatment effectiveness and potentially improve patient outcomes.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

This trial will evaluate the combination of tiragolumab, atezolizumab, and bevacizumab for non-small cell lung cancer (NSCLC). Research has shown that atezolizumab and bevacizumab have been studied in NSCLC and are generally safe. Atezolizumab aids the immune system in attacking cancer cells, while bevacizumab slows tumor growth by cutting off its blood supply. However, adding tiragolumab to this mix has not significantly improved outcomes in other cancers, such as liver cancer. Previous studies in NSCLC also found no major survival benefits when combining tiragolumab with atezolizumab. Despite these challenges, researchers continue to explore the potential of this combination for NSCLC. ^{1 2 3 4 6}

Who Is on the Research Team?

Joshua Reuss, MD

Principal Investigator

Georgetown University

Are You a Good Fit for This Trial?

Adults with advanced non-squamous NSCLC that's progressed after treatment can join. They must have a certain level of PD-L1 expression, not be pregnant or breastfeeding, and agree to use contraception. People with severe heart disease, recent infections, prior TIGIT therapy, or uncontrolled hypertension are excluded.

Inclusion Criteria

Signed Informed Consent Form (ICF)

Ability to comply with the study protocol, in the investigator's judgment

My condition worsened despite treatment targeting EGFR.

Exclusion Criteria

My high blood pressure is not well controlled.

I do not have any health issues that prevent me from taking experimental medications.

I stopped immunotherapy permanently due to severe side effects.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tiragolumab, atezolizumab, and bevacizumab every 3 weeks until progressive disease or unacceptable toxicity

9 months

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Bevacizumab
• Tiragolumab

Trial Overview The trial tests Tiragolumab combined with Atezolizumab and Bevacizumab in patients whose NSCLC has worsened despite previous treatments. It aims to assess the effectiveness of this combination therapy.

How Is the Trial Designed?

Group I: Tiragolumab plus atezolizumab and bevacizumab Experimental Treatment 3 Interventions

Tiragolumab 600mg IV will be administered together with atezolizumab 1200mg IV and bevacizumab 15mg/kg IV every 3 weeks (q3w) until progressive disease or unacceptable toxicity.

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?

Georgetown University

Lead Sponsor

Trials

355

Recruited

142,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

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]

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]

In a phase 2 study involving 199 treatment-naïve patients with advanced non-squamous non-small-cell lung cancer, the combination of cisplatin, pemetrexed, and bevacizumab (CisPemBev) showed a statistically significant improvement in progression-free survival (PFS) compared to carboplatin, paclitaxel, and bevacizumab (CarPacBev), with a median PFS of 7.6 months versus 7.0 months.

Both treatment regimens were well tolerated, but CisPemBev had a lower incidence of grade ≥3 adverse events (67%) compared to CarPacBev (82%), suggesting it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab plus platinum-based chemotherapy in advanced non-squamous non-small-cell lung cancer: a randomized, open-label phase 2 study (CLEAR). Udagawa, H., Sugiyama, E., Harada, T., et al.[2022]

In a study involving 987 patients with advanced non-small-cell lung cancer (NSCLC), bevacizumab combined with platinum-based chemotherapy showed a median progression-free survival of 7.4 months and an overall response rate of 45.6%, confirming its effectiveness as a first-line treatment.

The safety profile of bevacizumab was consistent with previous studies, with 33.6% of patients experiencing grade ≥3 adverse drug reactions, primarily leukopenia, neutropenia, and hypertension, but no new safety concerns were identified, indicating it is well tolerated even after more than 20 treatment cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AVAiLABLE NIS - AVASTIN® in lung cancer treatment in routine oncology practice in Germany. Zahn, MO., Linck, D., Losem, C., et al.[2020]

In a study involving 1187 patients with nonsquamous non-small-cell lung cancer, the combination of atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) showed a tolerable safety profile compared to other treatment regimens, with manageable adverse events during both induction and maintenance phases.

Patient-reported outcomes indicated that all treatment regimens, including ABCP, did not lead to significant declines in quality of life or physical functioning, suggesting that the addition of atezolizumab does not substantially increase the treatment burden for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Patient-Reported Outcomes of Atezolizumab Plus Chemotherapy With or Without Bevacizumab Versus Bevacizumab Plus Chemotherapy in Non-Small-Cell Lung Cancer. Reck, M., Wehler, T., Orlandi, F., et al.[2021]

Adagrasib combined with pembrolizumab shows promising efficacy for patients with newly diagnosed non-small cell lung cancer with a KRASG12C mutation, achieving overall response rates of 49% and 57% in two separate trials.

This drug combination demonstrated a favorable safety profile, exhibiting lower liver toxicity compared to other combinations of checkpoint inhibitors and targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frontline Promise for Adagrasib-Pembrolizumab Combination. [2023]

In a phase 3 study involving 692 patients with metastatic nonsquamous non-small-cell lung cancer (NSCLC), the combination of atezolizumab, bevacizumab, and chemotherapy significantly improved median progression-free survival to 8.3 months compared to 6.8 months with bevacizumab and chemotherapy alone.

The addition of atezolizumab also led to a longer median overall survival of 19.2 months versus 14.7 months in the control group, demonstrating its efficacy across various genetic backgrounds and PD-L1 expression levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC. Socinski, MA., Jotte, RM., Cappuzzo, F., 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]

The APPLE study is a phase 3 clinical trial designed to evaluate the effectiveness of adding bevacizumab to the combination of atezolizumab and platinum-based chemotherapy in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC).

The primary goal of the study is to assess progression-free survival in chemotherapy-naive patients, which could potentially establish a new standard treatment if successful.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Rationale and Design for APPLE (WJOG11218L): A Multicenter, Open-Label, Randomized Phase 3 Study of Atezolizumab and Platinum/Pemetrexed With or Without Bevacizumab for Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer. Shiraishi, Y., Kishimoto, J., Tanaka, K., et al.[2021]

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]

In a study of 2212 patients with advanced non-small cell lung cancer, those over 65 years old showed similar safety and efficacy outcomes when treated with bevacizumab (Avastin) combined with standard chemotherapy, compared to younger patients.

Elderly patients had comparable overall survival (14.6 months) and time to disease progression (8.2 months) as younger patients, with no significant increase in adverse events, indicating that bevacizumab is a safe and effective treatment option for older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of first-line bevacizumab plus chemotherapy in elderly patients with advanced or recurrent nonsquamous non-small cell lung cancer: safety of avastin in lung trial (MO19390). Laskin, J., Crinò, L., Felip, E., et al.[2015]

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 a meta-analysis of 2210 patients with non-small cell lung cancer (NSCLC), high-dosage bevacizumab (15 mg/kg) significantly increased the risk of treatment-related deaths compared to chemotherapy alone, with a relative risk of 2.04.

Bevacizumab treatment was also linked to a higher incidence of severe adverse events (grade 3 or 4), particularly at the higher dosage, indicating that the risk of these serious side effects may depend on the dosage used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk profile of bevacizumab in patients with non-small cell lung cancer: a meta-analysis of randomized controlled trials. Cao, C., Wang, J., Bunjhoo, H., et al.[2022]

Citations

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Tiragolumab/Atezolizumab/Bevacizumab Fails to ... Tiragolumab plus atezolizumab and bevacizumab did not significantly improve PFS in advanced HCC compared to placebo with atezolizumab and ...

2. clinicaltrialsarena.com clinicaltrialsarena.com/analyst-comment/esmo-2025-rocliver-cancer-failures-liver-cancer/

Roche's TIGIT failures continue, this time in liver cancer The study evaluated the triplet therapy of Roche's TIGIT inhibitor tiragolumab with Tecentriq (atezolizumab) and Avastin (bevacizumab) in first- ...

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NCT04958811 | Tiragolumab With Atezolizumab Plus ... To evaluate the efficacy of tiragolumab with atezolizumab and bevacizumab in previously-treated advanced non-squamous NSCLC.

4. withpower.com withpower.com/trial/phase-3-carcinoma-non-small-cell-lung-9-2021-3104e

Tiragolumab + Atezolizumab + Bevacizumab for Non-Small ... Atezolizumab and Bevacizumab have been studied in patients with non-small cell lung cancer, showing manageable safety profiles. Atezolizumab can cause side ...

5. 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 ... The SKYSCRAPER-01 trial showed no statistically significant PFS and OS improvements with tiragolumab plus atezolizumab in PD-L1–high NSCLC ...

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How TECENTRIQ + Avastin ® (bevacizumab) May Help Read about the results and efficacy of TECENTRIQ® (atezolizumab) and Avastin® (bevacizumab) as a combination immunotherapy in treating hepatocellular carcinoma ...