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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the drug atezolizumab (Tecentriq) affects various cancer types based on genetic analysis of tumors. It aims to determine if specific genetic markers in the tumor's DNA and RNA can predict a positive response to the treatment. The study includes different cancer groups, such as breast, lung, and gastrointestinal cancers. Individuals with an incurable solid tumor who have already undergone a specific genetic analysis of their cancer's DNA and RNA might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research shows that atezolizumab, a treatment for various cancers, is generally well-tolerated by patients. In studies with breast cancer patients, common side effects included tiredness and nausea. About 3% of lung cancer patients experienced immune-related effects like lung inflammation. Patients with gastrointestinal cancer lived longer when atezolizumab was combined with another drug, though they also experienced common side effects like tiredness and skin rash.

For genitourinary cancers, atezolizumab was generally well-tolerated, showing similar safety across different cancer types. In gynecological cancers, it was well-tolerated with no new safety concerns. Sarcoma patients experienced side effects like muscle and joint pain and tiredness, similar to other uses of the drug.

In cases of cancer with an unknown origin, safety data was limited but generally matched findings in other cancers. For other rare cancers, atezolizumab had a tolerable safety profile, with some patients experiencing common side effects like tiredness and nausea.

Overall, while atezolizumab can cause some side effects, its safety is generally consistent across different cancers. This is a Phase 2 trial, indicating that atezolizumab has already passed initial safety checks. However, participants should still consider potential risks and discuss them with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cancer?

Researchers are excited about Atezolizumab because it represents a new frontier in cancer treatment. Unlike traditional chemotherapy, which targets all rapidly dividing cells, Atezolizumab is an immunotherapy that works by unleashing the body's own immune system to specifically target and destroy cancer cells. This is achieved by inhibiting the PD-L1 protein, which some cancer cells use to evade immune detection. This precision in targeting cancer cells promises to not only be more effective but also reduce the side effects associated with attacking healthy cells. This innovative mechanism of action makes Atezolizumab a promising option for various cancer types, including breast, lung, and gastrointestinal cancers.

What evidence suggests that this trial's treatments could be effective for cancer?

Research has shown that atezolizumab holds promise for treating various types of cancer. In this trial, participants will be grouped into cohorts based on their primary tumor type, such as breast, lung, gastrointestinal, genitourinary, gynecological, sarcoma, primary unknown, and other cancers.

For breast cancer, studies have found that patients taking atezolizumab tend to live longer. In lung cancer, atezolizumab has helped patients with advanced stages live longer, with an average survival time of over 19 months. In gastrointestinal cancers, combining atezolizumab with other treatments has led to nearly half of the patients experiencing tumor shrinkage. Atezolizumab has also significantly improved survival rates in genitourinary cancers, reducing the risk of death by 41%. In sarcoma, about 40% of patients saw their tumors shrink, indicating its potential effectiveness. While atezolizumab has shown positive results in these cancers, each person's response can differ based on their specific cancer type. ^{5 6 7 8 9}

Who Is on the Research Team?

Janessa Laskin, MD

Principal Investigator

BC Cancer

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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, 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, 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]

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 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, 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 (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 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]

Citations

1. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2813177

Atezolizumab in Combination With Carboplatin and ... In this multicenter phase 2 randomized clinical trial, adding atezolizumab to carboplatin significantly increased PFS and OS in patients with ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12283416/

Peri-operative atezolizumab in early-stage triple-negative ... Long-term outcomes favored the atezolizumab group (event-free survival hazard ratio (HR), 0.76; 95% confidence interval (CI), 0.47–1.21; disease ...

3. targetedonc.com targetedonc.com/view/long-term-outcomes-bolstered-by-atezolizumab-in-early-stage-triple-negative-breast-cancer

Long-Term Outcomes Bolstered by Atezolizumab in Early- ... The latest analysis reveals that long-term outcomes consistently favored the atezolizumab group across all survival endpoints. While the trial ...

4. appliedclinicaltrialsonline.com appliedclinicaltrialsonline.com/view/tecentriq-trial-post-surgery-triple-negative-breast-cancer

Tecentriq Falls Short in Phase III Trial in Post-Surgery ... Tecentriq (atezolizumab) added to postoperative chemotherapy was not found to improve treatment outcomes for patients with high-risk early-stage triple- ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11783246/

Adjuvant Atezolizumab for Early Triple-Negative Breast Cancer Compared with chemotherapy alone, atezolizumab plus chemotherapy was associated with more treatment-related grade 3 or 4 adverse events (54% vs ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2019/761034s021lbl.pdf

Atezolizumab - accessdata.fda.gov The safety of TECENTRIQ was evaluated in ... The most common side effects of TECENTRIQ when used in triple-negative breast cancer with paclitaxel protein-.

7. tecentriq.global tecentriq.global/home/indication/triple-negative-breast-cancer.html

Triple-negative breast cancer - tecentriq See TECENTRIQ indication and review efficacy and safety data for TECENTRIQ + nab-paclitaxel from the Phase 3 IMpassion130 trial in patients with advanced ...

8. ema.europa.eu ema.europa.eu/en/medicines/human/EPAR/tecentriq

Tecentriq | European Medicines Agency (EMA) In addition, patients given the Tecentriq combination lived for 5.2 months on average without their disease getting worse compared with 4.3 months for patients ...

9. tecentriq-hcp.com tecentriq-hcp.com/

TECENTRIQ® (atezolizumab) HCP | Efficacy, Safety, PI & MOA Based on its mechanism of action, TECENTRIQ can cause fetal harm when administered to a pregnant woman. There are no available data on the use of TECENTRIQ in ...