Atezolizumab After Adoptive Cell Transfer for Cancer

Recruiting at 8 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Immunostimulants

Disqualifiers: CNS metastases, Severe infections, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 17

Duration: 12 months

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This pilot phase I trial studies the side effects of atezolizumab in treating patients with cancer following adoptive cell transfer. 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.

Will I have to stop taking my current medications?

The trial requires that you stop any anti-cancer therapy, including adoptive cell transfer, for 28 days before starting atezolizumab. Additionally, you must not take systemic immunosuppressive medications within 2 weeks before starting the trial. Other medications, like hormone-replacement therapy or oral contraceptives, are allowed.

What data supports the effectiveness of the drug Atezolizumab (Tecentriq) for cancer treatment?

Atezolizumab has shown promising results in treating various cancers, including bladder cancer, where it improved response rates and survival compared to other treatments. It has also been effective in non-small cell lung cancer and triple-negative breast cancer, leading to its approval for these conditions. ^{1 2 3 4 5}

Is atezolizumab generally safe for humans?

Atezolizumab, also known as Tecentriq, has been approved for use in several cancers and is generally considered to have an acceptable safety profile. Common side effects include fatigue, decreased appetite, and nausea, while more serious but less common effects can include lung inflammation, liver inflammation, and thyroid issues. ^{4 6 7 8 9}

How is the drug atezolizumab unique in cancer treatment?

Atezolizumab is unique because it is a monoclonal antibody that targets PD-L1, a protein that helps cancer cells evade the immune system. By blocking this protein, atezolizumab enhances the body's immune response against tumors, making it different from traditional chemotherapy that directly targets cancer cells. ^{1 2 4 5 10}

Research Team

Marcus Butler

Principal Investigator

University Health Network Princess Margaret Cancer Center LAO

Eligibility Criteria

Adults with advanced cancers not responding to standard treatments, who've had adoptive cell transfer (ACT), can join. They need a life expectancy over 3 months, certain blood and organ function levels, no recent cancer therapies except ACT, and measurable disease. Pregnant women or those with severe allergies to antibodies, active infections, or autoimmune diseases that could worsen are excluded.

Inclusion Criteria

My leukemia or lymphoma can be measured for treatment response.

My side effects from previous cancer treatments are mild, except for possible hair loss, skin changes, or hormone issues.

I agree to use birth control during and 5 months after the study due to risks to a fetus.

Exclusion Criteria

I haven't had chemotherapy or radiotherapy in the last 4 weeks and have recovered from any side effects.

I haven't taken any immune-weakening medications in the last 2 weeks.

I do not have any serious illnesses or social situations that would stop me from following the study's requirements.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atezolizumab intravenously over 30-60 minutes on day 1, with cycles repeating every 21 days for a total of 17 doses over up to 12 months

12 months

17 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 4 weeks, 8 weeks, and then every 3 months

Up to 1 year

Multiple visits (in-person)

Treatment Details

Interventions

• Atezolizumab

Trial Overview The trial is testing Atezolizumab's safety in patients after ACT therapy. It involves imaging tests like MRI and CT scans before and after treatment to see how the cancer responds. The study also includes biopsies and lab analyses to understand the drug's effects on tumors.

Participant Groups

Group I: Treatment (atezolizumab) Experimental Treatment 6 Interventions

Patients receive atezolizumab IV over 30- 60 minutes on day 1. Cycles repeat every 21 days for a total of 17 doses over up to 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and biopsy on study. Patients also undergo blood sample collection on study.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]

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]

Atezolizumab, an inhibitor of PD-L1, was found to be well tolerated in a phase 1-2 trial involving 90 children and young adults with refractory or relapsed solid tumors, with no fatal adverse events reported.

While only 5% of patients achieved an objective response, the study showed comparable serum concentrations of atezolizumab between children and young adults, suggesting potential for future research into optimizing immune checkpoint inhibitors for specific patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for children and young adults with previously treated solid tumours, non-Hodgkin lymphoma, and Hodgkin lymphoma (iMATRIX): a multicentre phase 1-2 study. Geoerger, B., Zwaan, CM., Marshall, LV., et al.[2020]

Atezolizumab, an immune checkpoint inhibitor used for treating non-small cell lung cancer, can cause rare but serious immune-related adverse events (irAEs) such as acute kidney injury (AKI) and immune thrombocytopenic purpura (ITP).

In a case study of a patient receiving atezolizumab, the development of AKI and ITP occurred one week after treatment initiation, but with appropriate management including IVIG and steroids, the patient's condition improved and was discharged for routine follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible atezolizumab-associated acute kidney injury and immune thrombocytopenia. Yılmaz, A., Mirili, C., Bilici, M., et al.[2022]

Atezolizumab (Tecentriq) is an FDA-approved treatment for unresectable or metastatic alveolar soft part sarcoma (ASPS), showing a 24% overall response rate in a clinical trial with 49 patients, and a durable response rate of 67% at 6 months and 42% at 12 months.

The treatment has a manageable safety profile, with common severe side effects including musculoskeletal pain (8%) and hypertension (6%), making it a viable option for patients with limited treatment alternatives for this high-risk disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab as the First Systemic Therapy Approved for Alveolar Soft Part Sarcoma. Bergsma, EJ., Elgawly, M., Mancuso, D., et al.[2023]

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, a monoclonal antibody targeting PD-L1, showed a 23% response rate and a median overall survival of 15.9 months in 119 patients with metastatic urothelial cancer who were unfit for cisplatin, indicating its efficacy as a front-line treatment.

In patients whose tumors progressed after first-line chemotherapy, atezolizumab had a 15% response rate and a median overall survival of 7.9 months, with better outcomes (26% response rate) in those with high PD-L1 expression, demonstrating its potential effectiveness based on biomarker status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Atezolizumab (Tecentriq®): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. Bernard-Tessier, A., Bonnet, C., Lavaud, P., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

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

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

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]

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

Atezolizumab in patients with advanced non-small cell lung cancer and history of asymptomatic, treated brain metastases: Exploratory analyses of the phase III OAK study. [2019]

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

Atezolizumab: First Global Approval. [2019]

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

FIR: Efficacy, Safety, and Biomarker Analysis of a Phase II Open-Label Study of Atezolizumab in PD-L1-Selected Patients With NSCLC. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Atezolizumab for children and young adults with previously treated solid tumours, non-Hodgkin lymphoma, and Hodgkin lymphoma (iMATRIX): a multicentre phase 1-2 study. [2020]

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

Possible atezolizumab-associated acute kidney injury and immune thrombocytopenia. [2022]

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

Atezolizumab as the First Systemic Therapy Approved for Alveolar Soft Part Sarcoma. [2023]

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

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

10. France pubmed.ncbi.nlm.nih.gov

[Atezolizumab (Tecentriq®): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. [2019]