Atezolizumab + Bevacizumab for Liver and Lung Cancers

Overseen By Adrian Sacher, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must not be taking: NSAIDs, Anticoagulants, Immunosuppressants, others

Disqualifiers: Hypertension, Cardiovascular disease, CNS metastases, 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: Until disease progression

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of the drugs atezolizumab (an immunotherapy drug known as Tecentriq) and bevacizumab (a targeted therapy drug known as Avastin) for individuals with inoperable liver cancer or lung cancer that has spread to the liver. The researchers aim to determine how long these treatments can prevent cancer progression. Participants will be divided into groups to receive different combinations of these drugs, and the study will collect blood and tumor samples to monitor changes. Suitable candidates for this trial include those diagnosed with inoperable liver cancer or non-small cell lung cancer that has spread to the liver, whether they have undergone previous chemotherapy or are new to treatment. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to significant advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial requires a 2-week period without chemotherapy, tyrosine kinase inhibitors, and palliative-dose radiotherapy before starting. Some medications like certain blood thinners and NSAIDs must be stopped 10 days before 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 bevacizumab is generally well-tolerated by patients with advanced liver cancer. In past studies, this combination improved survival rates without introducing new safety issues. Common side effects included fatigue and high blood pressure, but these were usually manageable.

For lung cancer, this drug combination has also yielded positive results. Studies found that patients experienced similar manageable side effects, such as fatigue and high blood pressure.

Atezolizumab alone has been tested in lung cancer patients as well. It improved survival, with side effects that most people can handle, such as fatigue and decreased appetite.

Overall, the safety of atezolizumab, with or without bevacizumab, has remained consistent across different studies. This consistency indicates that the side effects are known and usually manageable for most patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Atezolizumab and Bevacizumab for liver and lung cancers because these treatments work together to boost the immune system's ability to fight cancer cells. Unlike traditional chemotherapy, which directly targets and kills cancer cells, Atezolizumab is an immunotherapy that blocks a protein called PD-L1, helping the immune system recognize and attack cancer cells. Meanwhile, Bevacizumab, an anti-angiogenic drug, inhibits the growth of new blood vessels that tumors need to grow. This dual approach not only aims to attack the cancer from multiple angles but also has the potential to improve outcomes by leveraging the body's own defenses.

What evidence suggests that this trial's treatments could be effective for liver and lung cancers?

In this trial, participants with liver cancer in Arm A will receive a combination of atezolizumab and bevacizumab. Research has shown that using these drugs together effectively treats advanced liver cancer, reducing the risk of death by 42% compared to sorafenib. This combination also extends patient survival and slows tumor growth.

For lung cancer, participants in Arm B will receive both atezolizumab and bevacizumab, while those in Arm C will receive atezolizumab alone. Research indicates that atezolizumab, either alone or with bevacizumab, can improve survival rates for lung cancer that has spread to the liver. Specifically, atezolizumab alone has been shown to extend the lives of patients with non-small cell lung cancer. These treatments enhance the immune system's ability to fight cancer cells. ^{1 2 4 5 6}

Who Is on the Research Team?

Adrian G. Sacher

Principal Investigator

Princess Margaret Cancer Centre

Are You a Good Fit for This Trial?

Adults with inoperable liver cancer or non-small cell lung cancer that has spread to the liver, who have adequate organ function and are not pregnant. NSCLC patients must be EGFR/ALK wild type and HCC patients may have had prior treatments. Participants need a measurable lesion, controlled hepatitis B or C, an ECOG performance status of 0 or 1, and agree to use effective contraception.

Inclusion Criteria

I have recovered from side effects of previous treatments, except for hair loss or changes in skin color.

I have liver cancer and may or may not have been treated with specific cancer drugs before.

Agrees to use use highly effective contraceptive methods, not donate egg or sperm, during study participation, and for at least 6 months after the last dose of study medications

Exclusion Criteria

I am currently in a clinical trial or was in one within the last 4 weeks.

I currently have active tuberculosis.

I have a history of specific lung conditions or signs of lung inflammation on a recent CT scan.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atezolizumab and/or bevacizumab every 3 weeks

Until disease progression

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Bevacizumab

Trial Overview The trial is testing the effectiveness of Atezolizumab alone or combined with Bevacizumab for treating liver cancer or lung cancer with liver metastases by monitoring how long it takes for participants' cancers to worsen after starting treatment. It also involves analyzing blood and tumor tissue samples before and after administration.

How Is the Trial Designed?

Group I: Arm C (Lung Cancer) Experimental Treatment 1 Intervention

Atezolizumab: 1200 mg, intravenously (IV), every 3 weeks

Group II: Arm B (Lung Cancer) Experimental Treatment 2 Interventions

Atezolizumab: 1200 mg, intravenously (IV), every 3 weeks Bevacizumab: 15 mg/kg, intravenously (IV), every 3 weeks

Group III: Arm A (Liver Cancer) Experimental Treatment 2 Interventions

Atezolizumab: 1200 mg, intravenously (IV), every 3 weeks Bevacizumab: 15 mg/kg, intravenously (IV), every 3 weeks

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?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Hoffmann-La Roche

Industry 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

Published Research Related to This Trial

In a study of 191 patients with unresectable hepatocellular carcinoma (HCC), the combination therapy of atezolizumab and bevacizumab showed similar overall survival and progression-free survival rates in older patients (≥65 years) compared to younger patients (<65 years), indicating its efficacy across age groups.

The safety profile of the combination therapy was comparable between older and younger patients, with similar rates of treatment-related adverse events, including severe adverse events, suggesting that older patients can tolerate this treatment as well as younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma. Vithayathil, M., D'Alessio, A., Fulgenzi, CAM., et al.[2023]

Atezolizumab plus bevacizumab (Atez/Bev) is safe and effective for treating elderly patients with unresectable hepatocellular carcinoma (HCC), as shown in a study of 317 patients where age did not negatively impact survival outcomes.

There were no significant differences in treatment-related adverse events between elderly and non-elderly patients, indicating that Atez/Bev can be administered safely across different age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of atezolizumab plus bevacizumab in elderly patients with hepatocellular carcinoma: A multicenter analysis. Tada, T., Kumada, T., Hiraoka, A., et al.[2022]

In the phase 3 IMbrave050 study involving 668 patients with high-risk hepatocellular carcinoma, adjuvant treatment with atezolizumab plus bevacizumab significantly improved recurrence-free survival compared to active surveillance, indicating its potential efficacy as a post-surgery treatment.

However, the treatment was associated with a higher incidence of severe adverse events (41% of patients) compared to the active surveillance group (13%), highlighting the need for careful consideration of the benefit-risk profile in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial. Qin, S., Chen, M., Cheng, AL., et al.[2023]

The combination of atezolizumab and bevacizumab has been shown to significantly increase overall survival in patients with advanced hepatocellular carcinoma (HCC) compared to sorafenib.

The FDA's approval of this combination therapy marks a significant advancement in the treatment of HCC, potentially changing how the disease is managed across all stages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus Bevacizumab: A Novel Breakthrough in Hepatocellular Carcinoma. Castet, F., Willoughby, CE., Haber, PK., et al.[2022]

In a study of 194 Chinese patients with unresectable hepatocellular carcinoma, the combination of atezolizumab and bevacizumab significantly improved overall survival (OS) and progression-free survival (PFS) compared to sorafenib, with a hazard ratio for OS of 0.44 and for PFS of 0.60.

While the combination treatment showed promising efficacy, it also resulted in a higher incidence of grade 3-4 adverse events (59.1%) compared to sorafenib (46.6%), with hypertension being the most common severe side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus Bevacizumab versus Sorafenib in the Chinese Subpopulation with Unresectable Hepatocellular Carcinoma: Phase 3 Randomized, Open-Label IMbrave150 Study. Qin, S., Ren, Z., Feng, YH., et al.[2022]

In a study of 286 patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab, treatment-related hypertension was linked to better progression-free survival, with a median of 12.6 months compared to 6.5 months for those without hypertension.

Conversely, treatment-related fatigue was associated with shorter overall survival, indicating that while hypertension may signal a positive response to treatment, fatigue could indicate poorer outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events as potential predictive factors of therapeutic activity in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab. Tada, T., Kumada, T., Hiraoka, A., et al.[2023]

Atezolizumab combined with bevacizumab demonstrated good efficacy in treating advanced hepatocellular carcinoma (HCC), with a pooled overall response rate of 26% and a median overall survival of 14.7 months based on a review of 23 studies involving 3168 patients.

The treatment was well-tolerated, with 83% of patients experiencing any grade adverse events, and 30% experiencing grade 3 or higher adverse events, indicating that while side effects are common, the combination therapy remains a viable first-line option for advanced HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of atezolizumab plus bevacizumab treatment for advanced hepatocellular carcinoma in the real world: a single-arm meta-analysis. Gao, X., Zhao, R., Ma, H., et al.[2023]

In a multicenter study of 121 patients with advanced hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Ate/Bev), the objective response rate was 24% and the disease control rate was 76%, demonstrating real-world efficacy similar to phase III trial results.

The most common severe side effect was an increase in aspartate aminotransferase levels (10.7%), and factors like elevated baseline neutrophil-to-lymphocyte ratio were linked to poorer progression-free and overall survival, indicating the need for careful monitoring in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of atezolizumab plus bevacizumab in Korean patients with advanced hepatocellular carcinoma. Cheon, J., Yoo, C., Hong, JY., et al.[2022]

Atezolizumab in combination with bevacizumab has been approved by the FDA for treating unresectable hepatocellular carcinoma (HCC), showing improved overall survival (OS) and progression-free survival (PFS) compared to sorafenib, with a hazard ratio of 0.58 for OS.

The combination therapy resulted in a median PFS of 6.8 months versus 4.3 months for sorafenib, although it was associated with a higher incidence of hemorrhage (25% vs. 17%), highlighting the need for careful monitoring of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Atezolizumab Plus Bevacizumab for the Treatment of Patients with Advanced Unresectable or Metastatic Hepatocellular Carcinoma. Casak, SJ., Donoghue, M., Fashoyin-Aje, L., et al.[2022]

The combination therapy of atezolizumab and bevacizumab shows potential as a treatment option for patients with both hepatocellular carcinoma and gastric adenocarcinoma.

This finding suggests a possible new approach for managing these concurrent cancers, although further studies are needed to confirm its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatocellular carcinoma with gastric adenocarcinoma treated with atezolizumab and bevacizumab. Suga, T., Kimura, Y., Furuya, K., et al.[2023]

In a study of 41 patients with advanced hepatocellular carcinoma who failed first-line treatment with atezolizumab and bevacizumab, the median post-first-line survival was 5.9 months, significantly influenced by liver function status after treatment failure.

Patients with better liver function (Child-Pugh A) had a median survival of 9.6 months compared to only 3.8 months for those with Child-Pugh B and 1.2 months for Child-Pugh C, highlighting the importance of liver reserve and the benefit of receiving second-line therapy, which improved survival to a median of 8.0 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognosis and treatment pattern of advanced hepatocellular carcinoma after failure of first-line atezolizumab and bevacizumab treatment. Chen, CT., Feng, YH., Yen, CJ., 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 of 1447 patients treated with tyrosine-kinase inhibitors for hepatocellular carcinoma, only 29% were eligible for the combination therapy of atezolizumab-bevacizumab based on the IMbrave-150 trial criteria, indicating limited real-world applicability.

Eligible patients showed a median overall survival of 14.9 months, which was longer than non-eligible patients, suggesting that those who meet the criteria have better baseline health and cancer characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential feasibility of atezolizumab-bevacizumab therapy in patients with hepatocellular carcinoma treated with tyrosine-kinase inhibitors. Stefanini, B., Bucci, L., Santi, V., et al.[2022]

Citations

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Clinical Review - Atezolizumab (Tecentriq) - NCBI The overall 5-year net survival for lung cancer from 2015 to 2017 was estimated to be 19% for men and 26% for women. The incidence of lung cancer begins to ...