Bevacizumab + Chemoimmunotherapy + Atezolizumab for Small Cell Lung Cancer

(BELIEVE Trial)

Recruiting at 2 trial locations

Overseen By Amy Oppenheim

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Kamya Sankar

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

Disqualifiers: Hypertension, Autoimmune disease, Cardiovascular, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 20

39 Participants Needed

Trial Summary

What is the purpose of this trial?

This clinical trial aims to assess whether the addition of bevacizumab to atezolizumab and chemotherapy can improve response to treatment and progression-free survival in patients with extensive-stage small cell lung cancer (ES-SCLC) with liver metastases. The main questions it aims to answer are: * In patients with ES-SCLC with liver metastases, can bevacizumab in combination with atezolizumab and chemotherapy prolong the length of time that the cancer does not progress? * Is bevacizumab safe and tolerable when combined with atezolizumab and chemotherapy in patients with ES-SCLC and liver metastases? The study treatment includes two phases: * Induction phase: bevacizumab will be administered in combination with atezolizumab and chemotherapy on a 21-day cycle for four cycles. * Maintenance: atezolizumab and bevacizumab will be administered every 21 days for up to 12 months, or until unacceptable toxicity or disease progression. Participants will undergo blood tests every 3 weeks and tumor assessments every 6 weeks.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications like high-dose aspirin, some anticoagulants, and systemic immunosuppressive medications are restricted. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

What data supports the effectiveness of the drug combination Bevacizumab, Atezolizumab, and chemotherapy for small cell lung cancer?

Research shows that adding atezolizumab to chemotherapy improves survival in patients with extensive-stage small cell lung cancer. Additionally, combining atezolizumab and bevacizumab with chemotherapy has shown effectiveness in treating other types of lung cancer, suggesting potential benefits for small cell lung cancer as well. ^{1 2 3 4 5}

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

Bevacizumab, also known as Avastin, has been studied for safety in various cancers, including non-small cell lung cancer. Common side effects include bleeding, high blood pressure, and protein in the urine, but these are usually manageable with standard care. Serious side effects are rare, and the treatment is generally considered safe when monitored properly. ^{6 7 8 9 10}

How is the drug Bevacizumab + Chemoimmunotherapy + Atezolizumab unique for treating small cell lung cancer?

This treatment is unique because it combines bevacizumab, which blocks blood vessel growth that tumors need, with atezolizumab, an immune therapy that helps the body attack cancer cells, and chemotherapy, offering a multi-faceted approach to treating small cell lung cancer. ^{3 11 12 13 14}

Research Team

Kamya Sankar, MD

Principal Investigator

Cedars-Sinai Cancer

Eligibility Criteria

This trial is for adults with extensive-stage small cell lung cancer (ES-SCLC) that has spread to the liver. They should not have had prior treatment for ES-SCLC, be in a stable condition (ECOG 0-2), and able to follow study procedures. Women must use birth control, and men agree to use condoms. People with certain health conditions or who've had specific treatments recently are excluded.

Inclusion Criteria

My EGFR mutant lung cancer has changed to small cell type and spread to my liver, and I haven't had chemotherapy or immunotherapy.

Women who could become pregnant must have a negative pregnancy test.

I have not been treated for extensive-stage small cell lung cancer before.

Exclusion Criteria

I have not received any live vaccines recently.

I have not had major surgery in the last 4 weeks.

I have not coughed up blood in the last month.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Bevacizumab is administered in combination with atezolizumab and chemotherapy on a 21-day cycle for four cycles

12 weeks

4 visits (in-person)

Maintenance

Atezolizumab and bevacizumab are administered every 21 days for up to 12 months, or until unacceptable toxicity or disease progression

12 months

16 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Bevacizumab

Trial Overview The trial tests if adding Bevacizumab to Atezolizumab plus chemotherapy improves how long patients with ES-SCLC and liver metastases live without their cancer getting worse. It includes an induction phase of all drugs for four cycles, followed by maintenance therapy up to 12 months or until side effects become too severe or the disease progresses.

Participant Groups

Group I: Experimental Treatment Experimental Treatment 1 Intervention

1. Induction (ABCE): Atezolizumab 1200 mg, Bevacizumab 15 mg/kg, Carboplatin AUC5, Etoposide 100 mg/m2, given IV Q3weeks 2. Maintenance (AB): Atezolizumab 1200 mg and Bevacizumab 15 mg/kg given IV Q3weeks for 1 year, or until disease progression, or unacceptable toxicity

Bevacizumab is already approved in European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

Kamya Sankar

Lead Sponsor

Trials

1

Recruited

40+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

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

VA Ann Arbor Healthcare System

Collaborator

Trials

19

Recruited

10,300+

Findings from Research

In a study of 518 patients with extensive small cell lung cancer (SCLC) receiving atezolizumab plus chemotherapy, the median overall survival was 11.3 months, with 46.7% of patients alive at 12 months, indicating the treatment's effectiveness in a real-world setting.

The study demonstrated that 23.6% of patients continued atezolizumab treatment beyond disease progression, suggesting a potential strategy for improving outcomes, particularly in patients with better performance status (PS 0/1) who had a median overall survival of 12.2 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effectiveness and treatment sequences in patients with extensive stage small cell lung cancer receiving atezolizumab plus chemotherapy: Results of the IFCT-1905 CLINATEZO real-world study. Falchero, L., Guisier, F., Darrason, M., et al.[2023]

The combination of atezolizumab, a PD-L1 inhibitor, with platinum-based chemotherapy significantly improves overall survival in patients with extensive-stage small cell lung cancer compared to chemotherapy alone.

This research suggests that this combination therapy could become a new first-line treatment option for patients suffering from this aggressive form of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study: Atezolizumab Improves Survival in SCLC. [2019]

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 a study of 99 previously untreated patients with extensive disease small cell lung cancer (ED-SCLC), adding atezolizumab to the standard carboplatin and etoposide regimen significantly improved overall survival, extending it to 20.8 months compared to 12.1 months for those receiving carboplatin and etoposide alone.

While there was no significant difference in progression-free survival between the two treatment groups, certain subgroups (such as older patients, males, and those with better health status) showed particularly enhanced survival benefits from the addition of atezolizumab, indicating its potential for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. Kubo, S., Kobayashi, N., Matsumoto, H., et al.[2023]

In a phase II study involving 72 patients with extensive-stage small-cell lung cancer, the combination of cisplatin, irinotecan, and bevacizumab resulted in a 75% overall response rate, with a median overall survival of 11.6 months and median progression-free survival of 7.0 months.

Although the primary endpoint of achieving a 50% to 65% 12-month survival rate was not met, the study found that patients who developed hypertension had improved overall survival, suggesting a potential link between hypertension and better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin, irinotecan, and bevacizumab for untreated extensive-stage small-cell lung cancer: CALGB 30306, a phase II study. Ready, NE., Dudek, AZ., Pang, HH., et al.[2022]

Bevacizumab, when combined with chemotherapy, significantly improves clinical outcomes and delays disease progression in patients with advanced non-squamous non-small-cell lung cancer (NSCLC), as demonstrated in pivotal phase III trials involving large patient populations.

The safety profile of bevacizumab is well-characterized, with manageable adverse events such as hypertension and bleeding, and the overall incidence of serious side effects is similar to that of placebo, indicating it can be safely administered in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging safety data for bevacizumab in advanced non-small-cell lung cancer. Hirsh, V.[2015]

Bevacizumab, when added to treatment for advanced non-small-cell lung cancer (NSCLC), significantly increases the risk of certain adverse events, specifically proteinuria, hypertension, and hemorrhagic events, based on a meta-analysis of 3,745 patients from nine clinical trials.

Despite these risks, the study found no significant increase in the likelihood of gastrointestinal perforation, thromboembolic events, or fatal outcomes, suggesting that while bevacizumab has associated risks, it does not lead to some of the more severe complications seen with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of adverse events with bevacizumab addition to therapy in advanced non-small-cell lung cancer: a meta-analysis of randomized controlled trials. Lai, XX., Xu, RA., Yu-Ping, L., 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]

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]

Bevacizumab therapy is associated with several adverse events, the most common being hypertension, which requires regular monitoring and management with antihypertensive medications during treatment.

Close monitoring for other serious complications, such as proteinuria and thromboembolic events, is crucial, as timely management can help prevent severe outcomes and improve patient safety throughout the course of therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Understanding and managing the possible adverse effects associated with bevacizumab. Shord, SS., Bressler, LR., Tierney, LA., et al.[2020]

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]

Bevacizumab (Avastin) is the first and only antiangiogenic therapy approved for treating non-small cell lung cancer (NSCLC), highlighting its unique role in this type of cancer treatment.

The review summarizes clinical trial results and offers practical prescribing advice for clinicians, emphasizing the importance of understanding bevacizumab's efficacy in thoracic oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Bevacizumab in thoracic oncology: results and practical aspects]. Dansin, É., Cousin, S., Lauridant, G., et al.[2015]

In a phase II trial involving 63 patients with extensive-stage small-cell lung cancer, the combination of bevacizumab with cisplatin and etoposide resulted in a 6-month progression-free survival rate of 30.2% and a median overall survival of 10.9 months, indicating improved efficacy compared to historical controls.

The treatment was generally well tolerated, with neutropenia being the most common side effect (57.8%), and only one case of severe pulmonary hemorrhage, suggesting that adding bevacizumab does not significantly increase toxicity compared to chemotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of cisplatin plus etoposide and bevacizumab for previously untreated, extensive-stage small-cell lung cancer: Eastern Cooperative Oncology Group Study E3501. Horn, L., Dahlberg, SE., Sandler, AB., et al.[2023]

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. Ireland pubmed.ncbi.nlm.nih.gov

Long-term effectiveness and treatment sequences in patients with extensive stage small cell lung cancer receiving atezolizumab plus chemotherapy: Results of the IFCT-1905 CLINATEZO real-world study. [2023]

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

Study: Atezolizumab Improves Survival in SCLC. [2019]

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

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

4. Germany pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. [2023]

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

Cisplatin, irinotecan, and bevacizumab for untreated extensive-stage small-cell lung cancer: CALGB 30306, a phase II study. [2022]

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

Emerging safety data for bevacizumab in advanced non-small-cell lung cancer. [2015]

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

Risk of adverse events with bevacizumab addition to therapy in advanced non-small-cell lung cancer: a meta-analysis of randomized controlled trials. [2022]

8. 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]

9. 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]

10. England pubmed.ncbi.nlm.nih.gov

Understanding and managing the possible adverse effects associated with bevacizumab. [2020]

11. England pubmed.ncbi.nlm.nih.gov

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

12. France pubmed.ncbi.nlm.nih.gov

[Bevacizumab in thoracic oncology: results and practical aspects]. [2015]

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

Phase II study of cisplatin plus etoposide and bevacizumab for previously untreated, extensive-stage small-cell lung cancer: Eastern Cooperative Oncology Group Study E3501. [2023]

14. 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]