Atezolizumab Dosing for Cancer

Overseen By James L Gulley, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunostimulatory agents, Immunosuppressive medications

Disqualifiers: Autoimmune disease, Severe allergies, 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: 14

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have taken certain investigational or immunostimulatory agents within a month before starting the study. It's best to discuss your specific medications with the trial team.

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

Atezolizumab has shown effectiveness in treating advanced bladder cancer and non-small cell lung cancer, with studies indicating improved survival rates and tumor response compared to other treatments. It works by boosting the immune system's ability to fight cancer cells, and its effectiveness is particularly notable in patients with higher levels of a specific protein (PD-L1) on their cancer cells. ^{1 2 3 4 5}

Is atezolizumab (Tecentriq) generally safe for humans?

Atezolizumab (Tecentriq) has been shown to have an acceptable safety profile in clinical trials for various cancers, including lung and bladder cancer. Common side effects include fatigue, decreased appetite, and nausea, while more serious side effects can include pneumonia and liver inflammation. Overall, it is considered to have a favorable toxicity profile. ^{3 4 6 7 8}

What makes the drug atezolizumab unique for cancer treatment?

Atezolizumab is unique because it targets a specific protein called PD-L1, helping the immune system recognize and attack cancer cells. It is administered as an intravenous infusion and offers flexible dosing schedules, which can be extended beyond the standard regimen without compromising effectiveness. ^{3 8 9 10 11}

What is the purpose of this trial?

Background: A type of drug called monoclonal antibody immune checkpoint inhibitors are often used in cancer treatment. These drugs help the body s immune system fight cancer by blocking proteins that cause cancer cells to grow. One of these drugs (atezolizumab) is approved to treat certain cancers. Researchers want to find out if lower doses of this drug might provide the same benefit with fewer adverse effects. Objective: To test different doses and timing of atezolizumab for people with cancer. Eligibility: People aged 18 years and older with cancer that has spread locally or to other organs. They must be eligible for treatment with the study drug. Design: Participants will be screened. They will have blood tests and imaging scans. They will provide a sample of tissue from their tumor. Atezolizumab is administered through a tube attached to a needle inserted into a vein in the arm. Participants will take this drug alone or combined with other drugs prescribed for their care. The first 2 treatments will be done per the FDA recommended dose and schedule. Before administering the second dose of the study drug, researchers will check the level of the drug in the participant s blood. Depending on those results, their 3rd dose will be scheduled 2 to 6 weeks later. For the 3rd dose of the study drug, participants will switch to the FDA minimum dosage. Dosages of any other drugs will not change. Researchers will continue to test the levels of the drug in participants blood before each treatment for 16 weeks. After that, these levels will be tested every 3 months. Study treatment may last up to 2 years.

Research Team

James L Gulley, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults aged 18+ with various advanced cancers (like lung, liver, melanoma) that have spread and are eligible for atezolizumab treatment can join. They must not be pregnant, breastfeeding (or willing to stop), and agree to use contraception. People with certain viral infections must have them under control. Those with a history of severe allergies or autoimmune diseases cannot participate.

Inclusion Criteria

My organs and bone marrow are functioning well.

I had hepatitis C but now have no detectable virus.

I agree to use effective birth control or remain abstinent during and up to 5 months after the study.

Exclusion Criteria

You have taken a non-approved experimental drug for your condition within the last 28 days.

You have had a bone marrow or solid organ transplant in the past.

You are allergic to Chinese hamster ovary cell products or any part of the atezolizumab medicine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Initial Treatment

Participants receive the FDA approved dose and frequency of atezolizumab for the first two doses

4-6 weeks

2 visits (in-person)

Therapeutic Drug Monitoring Treatment

Participants switch to 840 mg dose of atezolizumab with therapeutic drug monitoring to maintain target trough levels

16 weeks

8 visits (in-person)

Extended Monitoring

Participants continue to receive atezolizumab with dose adjustments every 3 months based on therapeutic drug monitoring

Up to 2 years

Every 3 months (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Atezolizumab

Trial Overview The trial is testing if lower doses of atezolizumab, an immune system-boosting drug used in cancer treatment, are as effective as standard doses but cause fewer side effects. Participants will receive the FDA recommended dose initially then switch to the minimum dosage while researchers monitor drug levels in their blood over time.

Participant Groups

Group I: Arm 1 Experimental Treatment 1 Intervention

Atezolizumab treatment course

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

In a study of 88 patients with relapsed/refractory non-small cell lung cancer receiving atezolizumab, tumor shrinkage was significantly correlated with the area under the curve (AUC) of the drug's pharmacokinetics, indicating that higher drug exposure may lead to better treatment outcomes.

Additionally, changes in interleukin (IL)-18 levels at day 21 were also linked to tumor response, suggesting that monitoring this biomarker could help predict the duration of the treatment's effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A PK/PD Analysis of Circulating Biomarkers and Their Relationship to Tumor Response in Atezolizumab-Treated non-small Cell Lung Cancer Patients. Netterberg, I., Li, CC., Molinero, L., et al.[2020]

Atezolizumab, an immune checkpoint inhibitor, has been shown to significantly prolong overall survival in patients with advanced non-small cell lung cancer (NSCLC) who have previously received chemotherapy, based on results from the phase II POPLAR and phase III OAK trials.

The treatment is particularly effective in patients with higher PD-L1 expression, demonstrating higher objective response rates, and it has a manageable safety profile with a low incidence of immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Previously Treated Advanced Non-Small Cell Lung Cancer. Blair, HA.[2020]

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 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, 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 (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, 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 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]

In a study of 27 lung cancer patients, the standard dosing of atezolizumab (1200 mg every 3 weeks) resulted in plasma levels significantly above the target engagement threshold of 6 μg/mL, with a mean trough level of 78.3 μg/mL, indicating potential overexposure.

Despite the high plasma levels, there was no increase in side effects, and the overall response rate was 55.5%, suggesting that dosing intervals could be safely extended to every 12 weeks or longer without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Killing a fly with a sledgehammer: Atezolizumab exposure in real-world lung cancer patients. Marolleau, S., Mogenet, A., Boeri, C., et al.[2023]

Atezolizumab shows consistent pharmacokinetics across various tumor types and treatment settings, whether used alone or in combination, supporting its flexible dosing regimens of 840 mg every 2 weeks, 1200 mg every 3 weeks, and 1680 mg every 4 weeks.

The efficacy of atezolizumab in combination therapies was found to be independent of drug exposure levels, and there was no significant increase in adverse events with higher doses, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extension of the Alternative Intravenous Dosing Regimens of Atezolizumab into Combination Settings through Modeling and Simulation. Liu, SN., Marchand, M., Liu, X., et al.[2022]

Extended dosing regimens of atezolizumab, such as 1200 mg every 6 weeks and 1680 mg every 8 weeks, show similar efficacy to the standard 1200 mg every 3 weeks regimen for treating non-small cell lung cancer and urothelial carcinoma, based on simulations of 746 patients.

All tested dosing regimens maintained serum concentrations above the effective target level, suggesting that these extended regimens could be safe and potentially beneficial for patients, without compromising treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Model-based simulation to support the extended dosing regimens of atezolizumab. Chou, CH., Hsu, LF.[2021]

References

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

A PK/PD Analysis of Circulating Biomarkers and Their Relationship to Tumor Response in Atezolizumab-Treated non-small Cell Lung Cancer Patients. [2020]

2. France pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Previously Treated Advanced Non-Small Cell Lung Cancer. [2020]

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

Atezolizumab: First Global Approval. [2019]

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

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

5. France pubmed.ncbi.nlm.nih.gov

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

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

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

7. 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]

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

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

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

Killing a fly with a sledgehammer: Atezolizumab exposure in real-world lung cancer patients. [2023]

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

Extension of the Alternative Intravenous Dosing Regimens of Atezolizumab into Combination Settings through Modeling and Simulation. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Model-based simulation to support the extended dosing regimens of atezolizumab. [2021]