Atezolizumab for Cancer

(CAPTIV-8 Trial)

Overseen By Janessa Laskin, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: British Columbia Cancer Agency

Must not be taking: PD-1/PD-L1 inhibitors, Immunosuppressants

Disqualifiers: Autoimmune disease, Severe infections, Cardiovascular disease, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 22

Duration: Variable, up to 54 months

200 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will investigate the effects of atezolizumab on select cancer types in people whose analysis of tumour DNA and RNA indicates they may be sensitive to atezolizumab. This study aims to determine if the information from the cancer genome analysis corresponds with the effects of atezolizumab on individuals and their cancer. This is a Phase 2 study, which is undertaken after preliminary safety testing on a drug is completed, and will involve approximately 200 participants. Participants are assigned to one of 8 cohorts based on their primary tumour type: breast, lung, gastrointestinal (GI), primary unknown, genitourinary (GU), sarcoma, gynecological, and 'other' cancer types. Participants in all cohorts will receive the same dose of atezolizumab (1200 mg every 3 weeks). In the first stage for each cohort, 8 participants will be enrolled and if no participants respond to treatment, enrollment to that cohort will be closed. If 1 or more participants respond to treatment, up to 16 additional participants will be enrolled to that cohort. Participants continue on treatment until they no longer may benefit from the treatment or they decide to stop treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, you cannot participate if you have taken certain treatments like systemic corticosteroids or immunosuppressive medications within 2 weeks before starting the trial. It's best to discuss your current medications with the trial team.

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

Atezolizumab has shown effectiveness in treating advanced bladder cancer, with a 15% response rate in patients whose cancer progressed after chemotherapy and a 24% response rate in those who were chemotherapy-naive. It has also been approved for use in non-small cell lung cancer and triple-negative breast cancer, demonstrating promising results in clinical trials. ^{1 2 3 4 5}

Is atezolizumab safe for humans?

Atezolizumab, also known as 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, its safety profile is considered favorable compared to other treatments. ^{1 2 3 6 7}

How is the drug Atezolizumab unique in treating cancer?

Atezolizumab is unique because it is an immune checkpoint inhibitor that targets PD-L1, helping the immune system attack cancer cells more effectively. It is used as a second-line therapy for certain cancers like bladder cancer and is the first immunotherapy approved for advanced triple-negative breast cancer when combined with nab-paclitaxel. ^{1 2 8 9 10}

Research Team

Janessa Laskin, MD

Principal Investigator

BC Cancer

Eligibility Criteria

Adults with incurable solid tumors who've had genome analysis suggesting sensitivity to Atezolizumab can join. They must have measurable disease, a life expectancy of at least 12 weeks, and good organ function. Women and men must agree to effective contraception. Exclusions include recent other treatments, certain health conditions like severe allergies or autoimmune diseases, active infections or HIV/HBV, significant heart issues, and prior PD-1/PD-L1 axis treatment.

Inclusion Criteria

Lymphocyte count ≥ 500/µL

Serum creatinine ≤ 1.5 × ULN

Participants must have measurable disease, as defined by RECIST 1.1.

Exclusion Criteria

I have a history of lung scarring or inflammation but not from radiation treatment.

I am not on steroids for brain disease but may be on stable anticonvulsants.

My condition is stable with only mild creams needed.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive atezolizumab (1200 mg every 3 weeks) until they no longer benefit or decide to stop

Variable, up to 54 months

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 weeks

Follow-up scan at 18 weeks

Long-term follow-up

Participants are monitored for progression-free survival and overall survival

Up to 54 months

Treatment Details

Interventions

• Atezolizumab

Trial Overview The trial tests Atezolizumab's effectiveness on various cancers (like breast, lung) in patients selected by tumor DNA/RNA analysis. It's a Phase 2 study with around 200 participants divided into cohorts based on cancer type. Each receives the same dose every three weeks until no longer beneficial or they choose to stop.

Participant Groups

Group I: Sarcoma Cohort Experimental Treatment 1 Intervention

Cohort of participants whose primary tumour type is sarcoma.

Group II: Primary Unknown Cohort Experimental Treatment 1 Intervention

Cohort of participants whose primary tumour type is unknown.

Group III: Other Cohort Experimental Treatment 1 Intervention

Cohort of participants whose primary tumour type is not classified as one of the other study arms. This cohort includes participants with cancers from the head and neck, skin, or rare cancers.

Group IV: Lung Cohort Experimental Treatment 1 Intervention

Cohort of participants whose primary tumour type is lung.

Group V: Gyne Cohort Experimental Treatment 1 Intervention

Cohort of participants whose primary tumour type is gynecological.

Group VI: GU Cohort Experimental Treatment 1 Intervention

Cohort of participants whose primary tumour type is genitourinary.

Group VII: GI Cohort Experimental Treatment 1 Intervention

Cohort of participants whose primary tumour type is gastrointestinal (including pancreas and hepatobiliary).

Group VIII: Breast Cohort Experimental Treatment 1 Intervention

Cohort of participants whose primary tumour type is breast.

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?

British Columbia Cancer Agency

Lead Sponsor

Trials

181

Recruited

95,900+

Hoffmann-La Roche

Industry Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Findings from Research

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, 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, an anti-PD-L1 therapy, showed long-term safety and efficacy in patients with metastatic urothelial carcinoma, with a median follow-up of 37.8 months and a low incidence of severe treatment-related adverse events (9%).

The treatment resulted in a 26% objective response rate, with a median duration of response of 22.1 months, and median overall survival of 10.1 months, particularly benefiting patients with higher PD-L1 expression on immune cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab (MPDL3280A) Monotherapy for Patients With Metastatic Urothelial Cancer: Long-term Outcomes From a Phase 1 Study. Petrylak, DP., Powles, T., Bellmunt, J., et al.[2022]

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 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, has shown significant improvements in progression-free and overall survival in patients with advanced non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) when combined with chemotherapy, as demonstrated in the IMpower studies.

The safety profile of atezolizumab in combination with chemotherapy is acceptable, with common immune-related adverse events including rash (18-28%), hypothyroidism (8-15%), and hepatitis (5-17%), consistent with its known effects as a single agent, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of atezolizumab plus chemotherapy for the treatment of metastatic lung cancer. Manzo, A., Carillio, G., Montanino, A., 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 is being studied as a neoadjuvant treatment for muscle-invasive bladder cancer (MIBC) in a phase II trial, where it is administered before radical cystectomy to evaluate its effectiveness based on the BASQ classification of tumor subtypes.

The trial aims to determine the objective pathological responses and 1-year progression-free survival rates in patients with MIBC, highlighting the potential of using molecular subtype characteristics to select the most responsive patient groups for atezolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of neoadjuvant atezolizumab treatment in patients with advanced urothelial bladder cancer according to the BASQ classification: a study protocol for an open-label, two-cohort, phase II trial. Yuk, HD., Jeong, CW., Kwak, C., et al.[2021]

Atezolizumab, combined with nab-paclitaxel, significantly improved progression-free survival in patients with advanced triple-negative breast cancer (TNBC) compared to placebo, based on the phase III IMpassion130 trial involving patients with unresectable locally advanced or metastatic TNBC.

While the combination therapy showed a tolerable safety profile, with common side effects like neutropenia and immune-related adverse events, it did not significantly affect health-related quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab (in Combination with Nab-Paclitaxel): A Review in Advanced Triple-Negative Breast Cancer. Kang, C., Syed, YY.[2020]

References

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

Atezolizumab: First Global Approval. [2019]

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

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

3. England pubmed.ncbi.nlm.nih.gov

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

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

Atezolizumab (MPDL3280A) Monotherapy for Patients With Metastatic Urothelial Cancer: Long-term Outcomes From a Phase 1 Study. [2022]

5. 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]

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

The safety of atezolizumab plus chemotherapy for the treatment of metastatic lung cancer. [2022]

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

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

9. England pubmed.ncbi.nlm.nih.gov

Efficacy of neoadjuvant atezolizumab treatment in patients with advanced urothelial bladder cancer according to the BASQ classification: a study protocol for an open-label, two-cohort, phase II trial. [2021]

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

Atezolizumab (in Combination with Nab-Paclitaxel): A Review in Advanced Triple-Negative Breast Cancer. [2020]