Atezolizumab After Adoptive Cell Transfer for Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the safety and effectiveness of the drug atezolizumab for cancer patients who have previously undergone adoptive cell transfer (ACT). Atezolizumab, an immunotherapy, harnesses the body's immune system to combat cancer by potentially inhibiting tumor growth and spread. The trial targets cancer patients whose disease has metastasized or cannot be surgically removed and who have not responded to standard treatments. Participants will receive atezolizumab via IV every three weeks for up to a year, provided the treatment remains effective and does not cause severe side effects. As a Phase 1 trial, the research focuses on understanding the treatment's effects in humans, offering participants the chance to be among the first to receive this potentially groundbreaking therapy.

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.

Is there any evidence suggesting that atezolizumab is likely to be safe for humans?

Research has shown that atezolizumab, also known as Tecentriq, was generally well-tolerated in past studies. About 4.1% of participants reported pneumonitis, an inflammation of the lungs. This side effect can range from mild to serious, but it is uncommon.

Atezolizumab is already approved for certain types of lung cancer, indicating it has passed strict safety checks for those conditions. Although this trial explores a different use, its approval for other uses suggests that its safety profile is well-understood. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Atezolizumab is unique because it harnesses the power of the immune system to fight cancer by blocking a protein called PD-L1. This is different from traditional chemotherapy, which directly kills cancer cells but can also harm healthy cells. Researchers are excited about atezolizumab because it offers a targeted approach that might result in fewer side effects and potentially better outcomes for patients. Unlike standard treatments, atezolizumab is administered intravenously and specifically designed to help the immune system recognize and attack cancer cells more effectively.

What evidence suggests that atezolizumab might be an effective treatment for cancer?

Research has shown that atezolizumab, which participants in this trial will receive, can extend the lives of people with certain cancers, such as non-small cell lung cancer (NSCLC). In one study, patients who took atezolizumab lived for an average of 19.2 months. Another study found that it reduced the risk of death by 41% compared to those who received chemotherapy. Additionally, patients on atezolizumab experienced longer periods without their cancer worsening. These results suggest that atezolizumab aids the immune system in fighting cancer cells, potentially preventing them from growing and spreading. ^{1 5 6 7 8}

Who Is on the Research Team?

Marcus Butler

Principal Investigator

University Health Network Princess Margaret Cancer Center LAO

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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, 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, 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]

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 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, 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 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 (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]

Citations

1. tecentriq.com tecentriq.com/metastatic-nsclc/results/how-tecentriq-may-help.html

Effectiveness & Safety of TECENTRIQ® (atezolizumab) for ... Median overall survival (OS) was 19.2 months for patients taking TECENTRIQ® (atezolizumab. Median OS=the length of time from the start of treatment in a ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9716834/

updated long-term efficacy of atezolizumab in a diverse ... In patients with previously treated advanced or metastatic non-small cell lung cancer (NSCLC), atezolizumab therapy improves survival with manageable safety.

3. tecentriq-hcp.com tecentriq-hcp.com/metastatic-nsclc/efficacy/impower110-clinical-trial-results.html

IMpower110 Clinical Trial Results - TECENTRIQ-HCP.com 41% reduction in the risk of death vs chemotherapy · Median PFS was 8.1 months with TECENTRIQ (95% CI, 6.8, 11.0) vs 5.0 months with platinum-based chemotherapy ...

4. tecentriq.com tecentriq.com/nsclc-after-surgery/results/how-tecentriq-may-help.html

TECENTRIQ may prevent your PD-L1+ non-small cell lung ... TECENTRIQ may prevent your PD-L1+ non-small cell lung cancer from coming back · More people were alive with TECENTRIQ than with best supportive care · Important ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12563583/

Effectiveness of Atezolizumab in Addition to Chemotherapy in ... The data suggests that more cycles of atezolizumab are associated with improved clinical outcomes, both in terms of OS and PFS. ECOG-PS and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11575237/

Correlation of safety and efficacy of atezolizumab therapy ... In our analysis, pneumonitis was reported in 4.1% who received atezolizumab either alone or in combination. The rate of all grade pneumonitis ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32459597/

Safety and Patient-Reported Outcomes of Atezolizumab ... Results: Overall, 400 (ACP), 393 (ABCP), and 394 (BCP) patients were safety evaluable (ie, intention-to-treat population that received one or ...

8. roche.com roche.com/media/releases/med-cor-2021-05-20

Pivotal Phase III data at ASCO show Roche's Tecentriq ... Tecentriq improved disease-free survival by more than one-third in people with PD-L1-positive resectable early-stage lung cancer, ...