Temozolomide + Atezolizumab for Small Cell Lung Cancer

Recruiting at 4 trial locations

Overseen By Kimberly Cameron

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Dwight Owen

Must not be taking: Temozolomide

Disqualifiers: CNS metastases, Active infection, Autoimmune disease, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This phase II trial studies the effects of temozolomide and atezolizumab as second or third line treatment for patients with small cell lung cancer that has spread to other places in the body (metastatic) or has come back (recurrent). Chemotherapy drugs, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving temozolomide and atezolizumab as second or third line treatment may help prolong survival in patients with small cell lung cancer.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on certain treatments like chemotherapy, immunotherapy, or have had recent surgery, you may need to wait for a recovery period before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Atezolizumab for small cell lung cancer?

Atezolizumab, when combined with other chemotherapy drugs, has been shown to improve survival in patients with extensive-stage small cell lung cancer (ES-SCLC) compared to chemotherapy alone, according to a large trial. This combination is now considered a standard treatment option for ES-SCLC. ^{1 2 3 4 5}

Is the combination of Temozolomide and Atezolizumab safe for humans?

Atezolizumab has been shown to have an acceptable safety profile in clinical trials for various cancers, including non-small cell lung cancer and small-cell lung cancer. Common side effects include fatigue, decreased appetite, and nausea, while more serious effects can include pneumonia and liver inflammation. Temozolomide is also used in cancer treatment, but specific safety data for the combination with Atezolizumab is not detailed in the provided research. ^{1 4 5 6 7}

How is the drug combination of Temozolomide and Atezolizumab unique for treating small cell lung cancer?

This treatment combines Temozolomide, a chemotherapy drug, with Atezolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells by blocking the PD-L1 protein. This combination is unique because it pairs traditional chemotherapy with immunotherapy, potentially offering a new approach for small cell lung cancer, which has limited treatment options. ^{1 2 3 4 5}

Research Team

Dwight Owen, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with small cell lung cancer that has spread or returned after initial treatment. Participants must be able to take oral meds, have measurable disease, and a good performance status. They should not have had certain treatments recently and must agree to use contraception.

Inclusion Criteria

I have been mostly active and able to carry out all pre-disease activities up to 28 days before signing up.

I am a woman who can have children and I have a negative pregnancy test from the last two weeks.

My cancer can be measured by scans as per RECIST v1.1.

Exclusion Criteria

I do not have another cancer that could affect the trial's safety or results.

I am currently on medication for a serious infection.

I haven't had cancer treatments like chemotherapy or radiation in the last 2 weeks.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive atezolizumab intravenously and temozolomide orally in two different dosing schedules. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and every 3 months thereafter.

Up to 2 years

Treatment Details

Interventions

• Atezolizumab (PD-L1 Inhibitor)
• Temozolomide (Alkylating agents)

Trial Overview The study tests temozolomide (a chemotherapy drug) combined with atezolizumab (an immunotherapy antibody) as second or third line treatments in patients whose cancer has metastasized or recurred. The goal is to see if this combo can extend survival times.

Participant Groups

Group I: Cohort II (atezolizumab, temozolomide) Experimental Treatment 2 Interventions

Patients receive atezolizumab IV over 30-60 minutes on day 1. Patients also receive temozolomide PO QD on days 1-14 of cycle 1 and days 1-21 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Cohort I (atezolizumab, temozolomide) Experimental Treatment 2 Interventions

Patients receive atezolizumab IV over 30-60 minutes on day 1 and temozolomide PO QD on days 1-5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Dwight Owen

Lead Sponsor

Trials

6

Recruited

210+

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

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 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]

Atezolizumab, combined with carboplatin and etoposide, significantly improves overall survival and progression-free survival in patients with extensive-stage small cell lung cancer, based on data from the IMpower133 trial involving previously untreated patients.

The treatment regimen is generally well tolerated, with no new safety concerns identified, and it does not negatively impact patients' quality of life, making it a valuable first-line therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Extensive-Stage SCLC. Frampton, JE.[2021]

In a study of 47 patients with transformed small-cell lung cancer (T-SCLC), combining the PD-L1 inhibitor atezolizumab with chemotherapy resulted in a high objective response rate of 73% and significantly improved overall survival (20.2 months) compared to those who did not receive immunotherapy (7.9 months).

The combination therapy was well tolerated, showing a safety profile consistent with previous studies, suggesting it could be a promising treatment option for T-SCLC patients, particularly those with positive PD-L1 status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A potential treatment option for transformed small-cell lung cancer on PD-L1 inhibitor-based combination therapy improved survival. Zhang, CY., Sun, H., Su, JW., et al.[2023]

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 1 study involving 17 patients with relapsed or refractory small-cell lung cancer (SCLC), atezolizumab was generally well tolerated, with 64.7% experiencing any-grade treatment-related adverse events, the most common being fatigue.

Atezolizumab showed some antitumor activity, with a partial response in 5.9% of patients and a median overall survival of 5.9 months, suggesting potential benefits for patients with high T-effector gene signature and PD-L1 expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Activity and Safety of Atezolizumab in a Phase 1 Study of Patients With Relapsed/Refractory Small-Cell Lung Cancer. Chiang, AC., Sequist, LVD., Gilbert, J., et al.[2021]

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]

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]

References

1. 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]

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

Atezolizumab: A Review in Extensive-Stage SCLC. [2021]

3. Ireland pubmed.ncbi.nlm.nih.gov

A potential treatment option for transformed small-cell lung cancer on PD-L1 inhibitor-based combination therapy improved survival. [2023]

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

Atezolizumab: First Global Approval. [2019]

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

Clinical Activity and Safety of Atezolizumab in a Phase 1 Study of Patients With Relapsed/Refractory Small-Cell Lung Cancer. [2021]

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

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

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

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. [2020]