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

Recruiting at 1 trial location

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

42 Participants Needed

Trial Summary

What is the purpose of this trial?

To evaluate the efficacy of tiragolumab with atezolizumab and bevacizumab in previously-treated advanced non-squamous NSCLC.

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.

What data supports the effectiveness of the drug combination Tiragolumab, Atezolizumab, and Bevacizumab for treating non-small cell lung cancer?

Atezolizumab combined with bevacizumab and chemotherapy is already a standard treatment for advanced non-small cell lung cancer, showing effectiveness in improving patient outcomes. Additionally, Atezolizumab has been shown to reinvigorate anticancer immunity in patients with non-small cell lung cancer, making it a promising component of this drug combination. ^{1 2 3 4 5}

Is the combination of Tiragolumab, Atezolizumab, and Bevacizumab generally safe for humans?

Atezolizumab and Bevacizumab have been studied in patients with non-small cell lung cancer, showing manageable safety profiles. Atezolizumab can cause side effects like fatigue, decreased appetite, and nausea, while Bevacizumab has been associated with severe adverse events in some cases. No new safety concerns were identified in recent studies, but it's important to discuss potential risks with your doctor. ^{6 7 8 9 10}

What makes the drug combination of Tiragolumab, Atezolizumab, and Bevacizumab unique for treating non-small cell lung cancer?

This drug combination is unique because it combines Tiragolumab, a novel anti-TIGIT immune checkpoint inhibitor, with Atezolizumab, an anti-PD-L1 drug, and Bevacizumab, which blocks blood vessel growth, to potentially enhance the immune system's ability to fight non-small cell lung cancer. ^{2 5 11 12 13}

Research Team

Joshua Reuss, MD

Principal Investigator

Georgetown University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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 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]

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]

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]

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]

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 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]

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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. [2019]

2. China 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). [2022]

3. England 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. [2022]

4. England pubmed.ncbi.nlm.nih.gov

AVAiLABLE NIS - AVASTIN® in lung cancer treatment in routine oncology practice in Germany. [2020]

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

Frontline Promise for Adagrasib-Pembrolizumab Combination. [2023]

6. England 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. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Risk profile of bevacizumab in patients with non-small cell lung cancer: a meta-analysis of randomized controlled trials. [2022]

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

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. [2022]

9. United States 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. [2021]

10. United States 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). [2015]

11. England 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. [2022]

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

Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC. [2022]

13. United States 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. [2021]